Bacterial cells transmit memories to offspring

Bacterial cells can "remember" brief, temporary changes to their bodies and immediate surroundings, a new Northwestern University and University of Texas-Southwestern study has found.

And, although these changes are not encoded in the cell's genetics, the cell still passes memories of them to its offspring -- for multiple generations.

Not only does this discovery challenge long-held assumptions of how the simplest organisms transmit and inherit physical traits, it also could be leveraged for new medical applications. For example, researchers could circumvent antibiotic resistance by subtly tweaking a pathogenic bacterium to render its offspring more sensitive to treatment for generations.

The study will be published Wednesday (Aug. 28) in the journal Science Advances.

"A central assumption in bacterial biology is that heritable physical characteristics are determined primarily by DNA," said Northwestern's Adilson Motter, the study's senior author. "But, from the perspective of complex systems, we know that information also can be stored at the level of the network of regulatory relationships among genes. We wanted to explore whether there are characteristics transmitted from parents to offspring that are not encoded in DNA, but rather in the regulatory network itself. We found that temporary changes to gene regulation imprint lasting changes within the network that are passed on to the offspring. In other words, the echoes of changes affecting their parents persist in the regulatory network while the DNA remains unchanged."

Motter is the Charles E. and Emma H. Morrison Professor of Physics at Northwestern's Weinberg College of Arts and Sciences and director of the Center for Network Dynamics. The study's co-first authors are postdoctoral fellow Thomas Wytock and graduate student Yi Zhao, who are both members of Motter's laboratory. The study also involves a collaboration with Kimberly Reynolds, a systems biologist at the University of Texas Southwestern Medical Center.

Learning from a model organism

Since researchers first identified the molecular underpinnings of genetic code in the 1950s, they have assumed traits are primarily -- if not exclusively -- transmitted through DNA. However, after the completion of the Human Genome Project in 2001, researchers have revisited this assumption.

Wytock cites the World War II Dutch famine as a famous example pointing to the possibility of heritable, non-genetic traits in humans. A recent study showed that the children of men, who were exposed to the famine in utero, exhibited an increased tendency to become overweight as adults. But isolating the ultimate causes for this type of non-genetic inheritance in humans has proved challenging.

"In the case of complex organisms, the challenge lies in disentangling confounding factors such as survivor bias," Motter said. "But perhaps we can isolate the causes for the simplest single-cell organisms, since we can control their environment and interrogate their genetics. If we observe something in this case, we can attribute the origin of non-genetic inheritance to a limited number of possibilities -- in particular, changes in gene regulation."

The regulatory network is analogous to a communication network that genes use to influence each other. The research team hypothesized that this network alone could hold the key to transmitting traits to offspring. To explore this hypothesis, Motter and his team turned to Escherichia coli (E. coli), a common bacterium and well-studied model organism.

"In the case of E. coli, the entire organism is a single cell," Wytock said. "It has many fewer genes than a human cell, some 4,000 genes as opposed to 20,000. It also lacks the intracellular structures known to underlie the persistence of DNA organization in yeast and the multiplicity of cell types in higher organisms.Because E. coli is a well-studied model organism, we know the organization of the gene regulatory network in some detail."

Reversible stress, irreversible change

The research team used a mathematical model of the regulatory network to simulate the temporary deactivation (and subsequent reactivation) of individual genes in E. coli. They discovered these transient perturbations can generate lasting changes, which are projected to be inherited for multiple generations. The team currently is working to validate their simulations in laboratory experiments using a variation of CRISPR that deactivates genes temporarily rather than permanently.

But if the changes are encoded in the regulatory network rather than the DNA, the research team questioned how a cell can transmit them across generations. They propose that the reversible perturbation sparks an irreversible chain reaction within the regulatory network. As one gene deactivates, it affects the gene next to it in the network. By the time the first gene is reactivated, the cascade is already in full swing because the genes can form self-sustaining circuits that become impervious to outside influences once activated.

"It's a network phenomenon," said Motter, who is an expert in the dynamic behaviors of complex systems. "Genes interact with each other. If you perturb one gene, it affects others."

Although his team is deactivating genes to test the hypothesis, Motter is clear that different types of perturbations could cause a similar effect. "We also could have changed the cell's environment," he said. "It could be the temperature, the availability of nutrients or the pH."

The study also suggests that other organisms have the necessary elements to exhibit non-genetic heritability. "In biology, it's dangerous to assume anything is universal," Motter contends. "But, intuitively, I do expect the effect to be common because E. coli'sregulatory network is similar or simpler than those found in other organisms."

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Beethoven's genes reveal low predisposition for beat synchronization

Ludwig van Beethoven, one of the most celebrated musicians in human history, has a rather low genetic predisposition for beat synchronization, according to a Current Biologystudy co-authored by Vanderbilt University Medical Center (VUMC) and theMax Planck Institutes for Empirical Aesthetics in Frankfurt am Main, Germany, and for Psycholinguistics in Nijmegen, the Netherlands.

The question of to what extent are exceptional human achievements influenced by genetic factors dates back to the early days of human genetics but seems to be easier to address today as modern molecular methods make it possible to analyze DNA of individuals throughout history.

An international team of researchers analyzed Beethoven's DNA to investigate his genetic musical predisposition, an ability closely related to musicality, by using sequences from a 2023 study in which the composer's genetic material was extracted from strands of his hair.

"For Beethoven, we used his recently sequenced DNA to calculate a polygenic score as an indicator for his genetic predisposition for beat synchronization," said Tara Henechowicz, B.Mus.Hons, M.A., a current PhD Candidate at the University of Toronto, recent visiting graduate student with the Vanderbilt Human Genetics Program, and the paper's second author.

"Interestingly, Beethoven, one of the most celebrated musicians in history, had an unremarkable polygenic score for general musicality compared to population samples from the Karolinska Institute in Sweden and Vanderbilt's BioVU Repository," she said.

The authors noted that it would be wrong to conclude from Beethoven's low polygenic score that his musical abilities were unexceptional.

"Our aim was to use this as an example of the challenges of making genetic predictions for an individual who lived over 200 years ago," Henechowicz said.

"The mismatch between the DNA-based prediction and Beethoven's musical genius provides a valuable teaching moment, because it demonstrates that DNA tests cannot give us a definitive answer about whether a given child will end up being musically gifted."

Henechowicz said the study does not discount that DNA contributes to people's musical skills, noting that prior studies have found an average heritability, which is the proportion of individual differences explained by all genetic factors, of 42% for musicality.

"In the current era of 'big data' such as Vanderbilt's BioVU repository, we have had the opportunity to look in fine detail at large groups of people to uncover the genetic underpinnings of traits such as rhythm ability or being musically active. The current study and other recent work also suggest that environment plays a key role in musical ability and engagement as well," said co-author Reyna Gordon, PhD, associate professor of Otolaryngology at VUMC and graduate co-advisor to Henechowicz.

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Researchers identify gene involved in neuronal vulnerability in Alzheimer's disease

Early stages of neurodegenerative disorders are characterized by the accumulation of proteins in discrete populations of brain cells and degeneration of these cells. For most diseases, this selective vulnerability pattern is unexplained, yet it could yield major insight into pathological mechanisms. Alzheimer's disease (AD), the world-leading cause of dementia, is defined by the appearance of two hallmark pathological lesions, amyloid plaques (extracellular aggregates of Aβ peptides) and neurofibrillary tangles (intracellular aggregates of hyperphosphorylated tau, or NFTs). While plaques are widespread in the neocortex and hippocampus, NFTs follow a well-defined regional pattern that starts in principal neurons from the entorhinal cortex.

In a new study from Boston University Chobanian & Avedisian School of Medicine, researchers have identified a gene they believe may lead to the degeneration of the neurons that are most vulnerable to AD.

"We are trying to understand why certain neurons in the brain are particularly vulnerable during the earliest stages of AD. Why they accumulate and degenerate very early is unknown. We believe elucidating this vulnerability would allow for a new therapeutic avenue for AD," said corresponding author Jean-Pierre Roussarie, PhD, assistant professor of anatomy & neurobiology at the school.

In collaboration with leading computational genomic experts from Rice University, the BU researchers along with co-corresponding author, Patricia Rodriguez-Rodriguez, PhD, from Karolinska Institute, used cutting-edge analysis tools with machine learning to identify the gene DEK as possibly responsible for vulnerability of entorhinal cortex neurons.

They injected viruses into the entorhinal cortex of experimental models and neurons grown in the lab to manipulate levels of the DEK gene.

When they reduced the levels of the DEK gene, vulnerable neurons started to accumulate tau and to degenerate.

According to the researchers, preventing these neurons from degeneration by targeting DEK or proteins that collaborate with DEK, would prevent patients from developing memories loss and would curtail the disease before it spreads to larger areas of the brain.

"Given that entorhinal cortex neurons are necessary for the formation of new memories and since they are so vulnerable and the first to die, this explains why the first symptom of AD is the inability to form new memories," said Roussarie.

The researchers believe these findings are the first step in understanding how these fragile neurons die, yet they hope to uncover additional genes to fully understand what leads to the death of critical memory-forming neurons.

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How obesity dismantles our mitochondria

The number of people with obesity has nearly tripled since 1975, resulting in a worldwide epidemic. While lifestyle factors like diet and exercise play a role in the development and progression of obesity, scientists have come to understand that obesity is also associated with intrinsic metabolic abnormalities. Now, researchers from University of California San Diego School of Medicine have shed new light on how obesity affects our mitochondria, the all-important energy-producing structures of our cells.

In a study published January 29, 2023 in Nature Metabolism, the researchers found that when mice were fed a high-fat diet, mitochondria within their fat cells broke apart into smaller mitochondria with reduced capacity for burning fat.

Further, they discovered that this process is controlled by a single gene.

By deleting this gene from the mice, they were able to protect them from excess weight gain, even when they ate the same high-fat diet as other mice.

"Caloric overload from overeating can lead to weight gain and also triggers a metabolic cascade that reduces energy burning, making obesity even worse," said Alan Saltiel, PhD, professor in the Department of Medicine at UC San Diego School of Medicine.

"The gene we identified is a critical part of that transition from healthy weight to obesity."

Obesity, which affects more than 40% of adults in the United States, occurs when the body accumulates too much fat, which is primarily stored in adipose tissue.

Adipose tissue normally provides important mechanical benefits by cushioning vital organs and providing insulation.

It also has important metabolic functions, such as releasing hormones and other cellular signaling molecules that instruct other tissues to burn or store energy.

In the case of caloric imbalances like obesity, the ability of fat cells to burn energy starts to fail, which is one reason why it can be difficult for people with obesity to lose weight.

How these metabolic abnormalities start is among the biggest mysteries surrounding obesity.

To answer this question, the researchers fed mice a high-fat diet and measured the impact of this diet on their fat cells' mitochondria, structures within cells that help burn fat.

They discovered an unusual phenomenon. After consuming a high-fat diet, mitochondria in parts of the mice's adipose tissue underwent fragmentation, splitting into many smaller, ineffective mitochondria that burned less fat.

In addition to discovering this metabolic effect, they also discovered that it is driven by the activity of single molecule, called RaIA.

RaIA has many functions, including helping break down mitochondria when they malfunction.

The new research suggests that when this molecule is overactive, it interferes with the normal functioning of mitochondria, triggering the metabolic issues associated with obesity.

"In essence, chronic activation of RaIA appears to play a critical role in suppressing energy expenditure in obese adipose tissue," said Saltiel.

"By understanding this mechanism, we're one step closer to developing targeted therapies that could address weight gain and associated metabolic dysfunctions by increasing fat burning."

By deleting the gene associated with RaIA, the researchers were able to protect the mice against diet-induced weight gain.

Delving deeper into the biochemistry at play, the researchers found that some of the proteins affected by RaIA in mice are analogous to human proteins that are associated with obesity and insulin resistance, suggesting that similar mechanisms may be driving human obesity.

"The direct comparison between the fundamental biology we've discovered and real clinical outcomes underscores the relevance of the findings to humans and suggests we may be able to help treat or prevent obesity by targeting the RaIA pathway with new therapies," said Saltiel "We're only just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting."

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Evolution is not as random as previously thought

A groundbreaking study has found that evolution is not as unpredictable as previously thought, which could allow scientists to explore which genes could be useful to tackle real-world issues such as antibiotic resistance, disease and climate change.

The study, which is published in the Proceedings of the National Academy of Sciences (PNAS), challenges the long-standing belief about the unpredictability of evolution, and has found that the evolutionary trajectory of a genome may be influenced by its evolutionary history, rather than determined by numerous factors and historical accidents.

The study was led by Professor James McInerney and Dr. Alan Beavan from the School of Life Sciences at the University of Nottingham, and Dr. Maria Rosa Domingo-Sananes from Nottingham Trent University.

"The implications of this research are nothing short of revolutionary," said Professor McInerney, the lead author of the study.

"By demonstrating that evolution is not as random as we once thought, we've opened the door to an array of possibilities in synthetic biology, medicine, and environmental science."

The team carried out an analysis of the pangenome -- the complete set of genes within a given species, to answer a critical question of whether evolution is predictable or whether the evolutionary paths of genomes are dependent on their history and so not predictable today.

Using a machine learning approach known as Random Forest, along with a dataset of 2,500 complete genomes from a single bacterial species, the team carried out several hundred thousand hours of computer processing to address the question.

After feeding the data into their high-performance computer, the team first made "gene families" from each of the gene of each genome.

"In this way, we could compare like-with-like across the genomes," said Dr. Domingo-Sananes.

Once the families had been identified, the team analysed the pattern of how these families were present in some genomes and absent in others.

"We found that some gene families never turned up in a genome when a particular other gene family was already there, and on other occasions, some genes were very much dependent on a different gene family being present."

In effect, the researchers discovered an invisible ecosystem where genes can cooperate or can be in conflict with one another.

"These interactions between genes make aspects of evolution somewhat predictable and furthermore, we now have a tool that allows us to make those predictions," adds Dr. Domingo-Sananes.

Dr Beavan said: "From this work, we can begin to explore which genes "support" an antibiotic resistance gene, for example. Therefore, if we are trying to eliminate antibiotic resistance, we can target not just the focal gene, but we can also target its supporting genes.

"We can use this approach to synthesise new kinds of genetic constructs that could be used to develop new drugs or vaccines. Knowing what we now know has opened the door to a whole host of other discoveries."

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Could a drug prevent hearing loss from loud music and aging?

Researchers have found a gene that links deafness to cell death in the inner ear in humans -- creating new opportunities for averting hearing loss.

A person's hearing can be damaged by loud noise, aging and even certain medications, with little recourse beyond a hearing aid or cochlear implant.

But now, UCSF scientists have achieved a breakthrough in understanding what is happening in the inner ear during hearing loss, laying the groundwork for preventing deafness.

The research, published on Dec. 22, 2023, in the Journal of Clinical Investigation Insight, links animal studies on hearing loss with a rare type of inherited deafness in humans. In both cases, mutations to the TMTC4 gene trigger a molecular domino effect known as the unfolded protein response (UPR), leading to the death of hair cells in the inner ear.

Intriguingly, hearing loss from loud noise exposure or drugs such as cisplatin, a common form of chemotherapy, also stems from activation of the UPR in hair cells, suggesting that the UPR may underly several different forms of deafness.

There are several drugs that block the UPR -- and stop hearing loss -- in laboratory animals. The new findings make a stronger case for testing these drugs in people who are at risk of losing their hearing, according to the researchers.

"Millions of American adults lose their hearing due to noise exposure or aging each year, but it's been a mystery what was going wrong," said Dylan Chan, MD, PhD, co-senior author on the paper and director of the Children's Communication Center (CCC) in the UCSF Department of Otolaryngology. "We now have solid evidence that TMTC4 is a human deafness gene and that the UPR is a genuine target for preventing deafness."

How hair cells in the ear self-destruct

In 2014, Elliott Sherr, MD, PhD, director of the UCSF Brain Development Research Program and co-senior author of the paper, noticed that several of his young patients with brain malformations all had mutations to TMTC4. But laboratory studies of this gene soon presented a conundrum.

"We expected mice with TMTC4 mutations to have severe brain defects early on, like those pediatric patients, yet to our surprise, they seemed normal at first," Sherr said. "But as those animals grew, we saw that they didn't startle in response to loud noise. They had gone deaf after they had matured."

Sherr partnered with Chan, an expert on the inner ear, to look into what was happening to the mice, which looked like an accelerated version of age-related hearing loss in humans. They showed that mutations to TMTC4 primed hair cells in the ear to self-destruct, and loud noise did the same thing. In both cases, hair cells were flooded with excess calcium, throwing off the balance of other cellular signals, including the UPR.

But they found there was a way to stop this. ISRIB, a drug developed at UCSF to block the UPR's self-destruct mechanism in traumatic brain injury, prevented animals who were exposed to noise from going deaf.

The first adult human deafness gene

In 2020, scientists from South Korea, led by Bong Jik Kim, MD, PhD, connected Chan and Sherr's 2018 findings with genetic mutations they found in two siblings who were losing their hearing in their mid-20s. The mutations were in TMTC4 and matched what Chan and Sherr had seen in animals, although they were distinct from those in Sherr's pediatric neurology patients.

"It's rare to so quickly connect mouse studies with humans," Sherr said. "Thanks to our Korean collaborators, we could more easily prove the relevance of our work for the many people who go deaf over time."

Kim, an otolaryngologist at the Chungnam National University College of Medicine (Korea), facilitated the shipping of cells from those patients to UCSF. Sherr and Chan tested those cells for UPR activity and found that, indeed, this flavor of TMTC4 mutation turned on the destructive UPR pathway in a human context.

When Chan and Sherr mutated TMTC4 only in hair cells in mice, the mice went deaf. When they mutated TMTC4 in cells from individuals in the Korean family who hadn't gone deaf, and in laboratory human cell lines, the UPR drove the cells to self-destruct. TMTC4 was more than a deafness gene in mice -- it was a deafness gene in humans, too.

Translating a discovery to prevent deafness

Understanding TMTC4 mutations gives researchers a new way of studying progressive deafness, since it is critical for maintaining the health of the adult inner ear. The mutations mimic damage from noise, aging or drugs like cisplatin.

The researchers envision a future where people who must take cisplatin, or who have to be exposed to loud noises for their jobs, take a drug that dampens the UPR and keeps hair cells from withering away, preserving their hearing.

The science also suggests that the UPR could be targeted in other contexts where nerve cells become overwhelmed and die, including diseases long thought to be incurable, like Alzheimer's or Lou Gehrig's disease.

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Researchers, Coast Salish people analyze 160-year-old indigenous dog pelt in the Smithsonian's collection

Researchers from the Smithsonian's National Museum of Natural History led a new analysis that sheds light on the ancestry and genetics of woolly dogs, a now extinct breed of dog that was a fixture of Indigenous Coast Salish communities in the Pacific Northwest for millennia. Anthropologist Logan Kistler and evolutionary molecular biologist Audrey Lin analyzed genetic clues preserved in the pelt of "Mutton," the only known woolly dog fleece in the world, to pinpoint the genes responsible for their highly sought-after woolly fur.

The study's findings, published today, Dec. 14, in the journal Science, include interviews contributed by several Coast Salish co-authors, including Elders, Knowledge Keepers and Master Weavers, who provided crucial context about the role woolly dogs played in Coast Salish society.

"Coast Salish traditional perspective was the entire context for understanding the study's findings," said Kistler, the museum's curator of archaeobotany and archaeogenomics.

Coast Salish tribal nations in Washington state and British Columbia bred and cared for woolly dogs for thousands of years. Prized for their thick undercoats, the dogs were sheared like sheep and often kept in pens or on islands to carefully manage their breeding and to care for the canines' health and vitality. Coast Salish weavers used the dogs' wool to craft blankets and other woven items that served a variety of ceremonial and spiritual purposes. Woolly dogs themselves possessed spiritual significance and were often treated as beloved family members. As emblems for many Coast Salish communities, woolly dogs adorned woven baskets and other art forms.

By the mid-19th century, this once thriving dog wool-weaving tradition was in decline. In the late 1850s, naturalist and ethnographer George Gibbs cared for a woolly dog named Mutton. When Mutton died in 1859, Gibbs sent his pelt to the nascent Smithsonian Institution, where the fleece has resided ever since. However, few were aware of the pelt's existence until it was rediscovered in the early 2000s.

Lin first learned about Mutton when she was a Peter Buck postdoctoral fellow at the museum in 2021.

"When I saw Mutton in person for the first time, I was just overcome with excitement," said Lin, who is now a postdoctoral researcher at the American Museum of Natural History. "I had heard from some other people that he was a bit scraggly, but I thought he was gorgeous."

She was surprised to find out that virtually no work had been done on the genetics of woolly dogs, which disappeared around the turn of the 20th century. She teamed up with Kistler and they reached out to several Coast Salish communities to gauge their interest in working together on a potential research project on woolly dogs.

Many in the Coast Salish communities were eager to share their knowledge.

"We were very excited to participate in a study that embraces the most sophisticated Western science with the most established Traditional Knowledge," said Michael Pavel, an Elder from the Skokomish/Twana Coast Salish community in Washington, who remembers hearing about woolly dogs early in his childhood. "It was incredibly rewarding to contribute to this effort to embrace and celebrate our understanding of the woolly dog."

To complement the perspectives they received from Pavel and other Coast Salish people from British Columbia and Washington state (the text from their interviews is available in the study's supplementary materials), Lin, Kistler and their colleagues began analyzing Mutton's genetic code. They sequenced the woolly dog genome and compared it with the genomes of ancient and modern breeds of dogs to determine what set woolly dogs apart. They also identified certain chemical signatures called isotopes in Mutton's pelt to determine the dog's diet and teamed up with noted natural history illustrator Karen Carr to create a life-like reconstruction of what Mutton looked like in the 1850s. Carr's work is the first in-depth reconstruction of a Coast Salish woolly dog in nearly three decades.

Based on the genetic data, the team estimated that woolly dogs diverged from other breeds up to 5,000 years ago -- a date that lines up with archaeological remains from the region. They also discovered that Mutton was genetically similar to pre-colonial dogs from Newfoundland and British Columbia. The researchers estimate that nearly 85% of Mutton's ancestry can be linked to pre-colonial dogs. This ancient ancestry is surprising because Mutton lived decades after the introduction of European dog breeds. This makes it likely that Coast Salish communities continued to maintain woolly dogs' unique genetic makeup until right before the dogs were wiped out.

In total, the team analyzed more than 11,000 different genes in Mutton's genome to determine what gave woolly dogs their fluffy fleece and wool fibers that could be spun together to create yarn. They identified 28 genes that have links to hair growth and follicle regeneration. These included a gene that causes a woolly hair phenotype in humans, and another linked to curly hair in other dogs. Similar genes were even activated in the genomes of woolly mammoths.

However, Mutton's genetics could tell the researchers little about what caused the dogs to decline. Traditionally, scholars have speculated that the arrival of machine-made blankets to the region in the early 19th century made woolly dogs expendable. But insights from Pavel and other traditional experts revealed that it was improbable that such a central part of Coast Salish society could be replaced.

Instead, woolly dogs were likely doomed by numerous factors impacting the Coast Salish tribal nations after European settlers arrived. Due to disease and colonial policies of cultural genocide, displacement and forced assimilation, it likely became increasingly difficult or forbidden for Coast Salish communities to maintain their woolly dogs.

"It was thousands of years of very careful maintenance lost within a couple of generations," Lin said.

But despite their disappearance, the memory of woolly dogs is still embedded into Coast Salish society. And Pavel thinks their understanding of woolly dogs is only getting clearer thanks to the new research effort.

"All of our communities held a certain aspect of knowledge about the woolly dog," Pavel said. "But when woven together, as a result of participating in this study, we now have a much more complete understanding."

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'Shocking' discovery: Electricity from electric eels may transfer genetic material to nearby animals

The electric eel is the biggest power-making creature on Earth. It can release up to 860 volts, which is enough to run a machine. In a recent study, a research group from Nagoya University in Japan found electric eels can release enough electricity to genetically modify small fish larvae. They published their findings in PeerJ -- Life and Environment.

The researchers' findings add to what we know about electroporation, a gene delivery technique.

Electroporation uses an electric field to create temporary pores in the cell membrane.

This lets molecules, like DNA or proteins, enter the target cell.

The research group was led by Professor Eiichi Hondo and Assistant Professor Atsuo Iida from Nagoya University.

They thought that if electricity flows in a river, it might affect the cells of nearby organisms.

Cells can incorporate DNA fragments in water, known as environmental DNA.

To test this, they exposed the young fish in their laboratory to a DNA solution with a marker that glowed in the light to see if the zebrafish had taken the DNA.

Then, they introduced an electric eel and prompted it to bite a feeder to discharge electricity.

According to Iida, electroporation is commonly viewed as a process only found in the laboratory, but he was not convinced.

"I thought electroporation might happen in nature," he said.

"I realized that electric eels in the Amazon River could well act as a power source, organisms living in the surrounding area could act as recipient cells, and environmental DNA fragments released into the water would become foreign genes, causing genetic recombination in the surrounding organisms because of electric discharge."

The researchers discovered that 5% of the larvae had markers showing gene transfer.

"This indicates that the discharge from the electric eel promoted gene transfer to the cells, even though eels have different shapes of pulse and unstable voltage compared to machines usually used in electroporation," said Iida.

"Electric eels and other organisms that generate electricity could affect genetic modification in nature.."

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Researchers develop comprehensive genetic map for bison, discover gene responsible for albinism

A research team led by scientists from the Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS) has developed the most comprehensive genome yet for the North American bison, bringing the animal's genetic roadmap up to date with the latest genome sequencing technology. In doing so, the research team also discovered the gene responsible for albinism in bison.

The study -- recently published in G3: Genes, Genomes, and Genetics -- details the development of this high-resolution reference genome, which the researchers then used to produce the first test for genetic mutations, starting with the mutation responsible for albinism.

Albinism, a rare condition characterized by a lack of pigment in an animal's body, making them look white with red eyes, has historical significance in that albino bison have been recognized as a religious symbol for some Native American Indigenous tribes.

The study also lays the framework for determining other genetic variations that impact important bison traits, such as those that contribute to the health and production value of this species.

New Genome, New Possibilities

Dr. James Derr, a VMBS professor of veterinary pathobiology and genetics who led the research team that created the first bison genome back in 2015, assembled the team that developed this new reference genome. This team includes assistant professor of genetics Dr. Brian Davis, graduate student Sam Stroupe, and representatives from Texas Parks and Wildlife and the National Park Service.

"Because reference genomes can help researchers identify and characterize genes that are responsible for a large number of traits, this technology is used to do all kinds of things, including diagnosing health conditions and developing targeted treatments," Davis said.

The newest bison reference genome was developed using technology that allows researchers to create genomes based on DNA from hybrids, which are animals with DNA from two different species. In this case, the researchers used DNA from a type of bison-cow hybrid called an F1, or individuals with a perfect 50-50 split between its parents' DNA.

In general, F1 hybrids between bison and cattle are rare but have historically happened, since we now know that most bison herds in North America contain descendants of hybrids between bison and cattle -- a discovery that Derr and his research partners made last year.

"One day we got a call from Texas Parks and Wildlife saying they knew someone who had an F1 hybrid," Derr said. "It was the first fully documented, first-generation F1 hybrid I have seen in 25 years of working with bison. That's why we were able to do this."

To create the new bison genome, the researchers first sequenced the genome of the F1 hybrid as well as the bison mom and the domestic cattle father. With this information, they were able to separate bison DNA from the cattle DNA regions in the hybrid.

Since the cattle genome is already very advanced, it provided a reference for creating the new bison genome, helping to guide researchers in developing the complete high-resolution reference bison genome.

To prove the utility of the new genome, the team set out to discover which gene mutation was responsible for albinism in bison and to create a genetic test that could be used to identify carriers of that mutation.

The discovery is the first time anyone has successfully determined the gene mutation responsible for an observable trait in bison.

"We knew albinism was an inherited recessive trait, but we didn't know which gene was responsible," Stroupe said. "So, we sequenced the DNA from a few albino bison and compared them to those of normal coloration to find the mutation that causes albinism. As it turns out, the mutation causes an important enzyme to cease functioning correctly, which leads to the lack of skin pigmentation."

The Uniqueness Of Albino Bison

Many North American Indigenous peoples regard white bison as sacred entities with prophetic spiritual associations. While not all white bison have albinism, the birth of one is cause for celebration in some communities.

Despite this cultural significance, Derr isn't suggesting that people try to produce albino bison using genetic testing.

"Sadly, albino bison are often not very healthy," Derr said. "They tend to develop skin cancers, and they can develop other health problems as they age."

Albino bison are also different from white or tan bison that result from crossing bison with white cattle, particularly Charolais. These bison lack the red eyes and pink nose of true albinos.

Now that a more accurate bison genome exists, scientists can learn more about the genetic makeup of North America's bison population.

"The development of this new reference genome and the identification of a causative genetic mutation is exciting news for bison," Derr said. "It opens the doors for new discoveries and insights into bison genetics.

Read more at Science Daily

New secrets about cat evolution revealed

Researchers at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS) and an interdisciplinary team of collaborators have uncovered new information about the history of cat evolution explaining how cats -- including well-known species like lions, tigers, and domestic cats -- evolved into different species and shedding light on how different genetic changes in cats relate to survival abilities like the ability to smell prey.

By comparing genomes of several cat species, the project, published today in Nature Genetics, has helped researchers understand why cat genomes tend to have fewer complex genetic variations (such as rearrangements of DNA segments) than other mammal groups, like primates. It also revealed new insights into which parts of cat DNA are most likely to evolve rapidly and how they play a role in species differentiation.

"Our goal was to better understand how cats evolved and the genetic basis of the trait differences between cat species," said Dr. Bill Murphy, a VMBS professor of veterinary integrative biosciences who specializes in cat evolution. "We wanted to take advantage of some new technologies that allow us to create more complete cat genomic maps.

"Our findings will open doors for people studying feline diseases, behavior, and conservation," he said. "They'll be working with a more complete understanding of the genetic differences that make each type of cat unique."

Variations On A Theme

Among the things the scientists were trying to better understand is why feline chromosomes -- cellular structures containing the genetic information for traits like fur color, size, and sensory abilities -- are more stable than in other mammal groups.

"We've known for a while now that cat chromosomes across species are very similar to each other," Murphy said. "For example, the chromosomes of lions and domestic cats hardly differ at all. There appear to be far fewer duplications, rearrangements, and other types of variation than what are commonly found in great apes."

In the primate order, this kind of genetic variation has led to the evolution of different species -- including humans and great apes.

"The great ape genomes tend to break and rearrange, and even human genomes have very unstable regions," Murphy said. "These variations may predispose certain individuals to have genetic conditions, like autism and other neurological disorders."

The key to this variation between cats and apes, as Murphy found out, appears to be the frequency of something called segmental duplications -- segments of DNA that are highly similar copies of other DNA segments found elsewhere in the genome.

"Primate genome researchers have been able to link these segmental duplications to chromosome rearrangements," he said. The more segmental duplications you have in your DNA, the more likely the chromosomes are to rearrange, etc.

"What we discovered by comparing a large number of cat species genomes is that cats have just a fraction of the segmental duplications found in other mammal groups -- primates actually have seven times more of these duplications than cats. That's a big difference, and now we believe we understand why cat genomes are more stable," he said.

A Needle In A (Double) Helix

While cats may not have as many large genetic rearrangements in their DNA, they still have plenty of differences. Through their research, Murphy and his colleagues now better understand which parts of cat DNA cause those variations, especially the variations that define speciation, or the differences between species.

"It turns out that there's a large region on the center of the X chromosome where most of the genetic rearrangements are happening," Murphy said. "In fact, there's one specific repetitive element within this region called DXZ4 that evidence tells us is largely responsible for the genetic isolation of at least two cat species, the domestic and jungle cat."

DXZ4 is what Murphy calls a satellite repeat -- it's not a typical gene that codes for a physical trait like fur color, but, rather, it aids in the three-dimensional structure of the X chromosome and likely played an important role in cat speciation.

"We still don't know the precise mechanism, but by comparing all these cat genomes, we can better measure the rate at which DXZ4 evolved in one species compared to all the others. What we learned is that DXZ4 is one of the most rapidly evolving parts of the cat genome; it's evolving faster than 99.5% of the rest of the genome," he explained.

"Because of the rate at which it mutates, we were able to demonstrate why DXZ4 is probably linked to speciation," Murphy said.

Sniffing Out Elusive Genes

Using new, highly detailed genome sequences, the team also uncovered clearer links between the number of olfactory genes, which govern scent detection in cats and variation in social behavior and how they relate to their surroundings.

"Since cats are predators who rely heavily on smell to detect their prey, their sense of smell is a pretty important part of who they are," he said. "Cats are a very diverse family, and we've always wanted to understand how genetic variation plays a role in different cat species' ability to smell in their different environments.

"Lions and tigers have a pretty big difference between certain odorant genes involved in detecting pheromones, which are chemicals that different animals release into the environment to communicate information about identity, territory, or danger," Murphy said.

"We think the large difference has to do with lions being very social animals living in family groups and tigers living a solitary lifestyle. Lions may have a reduced reliance on pheromones and other odorants because they're constantly around other lions, reflected in the fewer genes of this type in their genomes," he said.

Tigers, on the other hand, need to be able to smell prey across very large territories as well as find mates.

"Tigers, in general, have large olfactory and pheromone receptor repertoires," Murphy said. "We think this is directly tied to the size of their territories and the variety of environments in which they live."

Domestic cats, on the other hand, appear to have lost a wide range of olfactory genes.

"If they don't have to travel as far to find what they need because they're living with people, it makes sense that natural selection wouldn't preserve those genes," he said.

Murphy shared that his favorite example from the project is the odorant receptors from the fishing cat, an aquatically adapted wild cat species living in Southeast Asia.

"We were able to show that fishing cats have retained many genes for detecting waterborne odorants, which is a pretty rare trait in terrestrial vertebrates," he said. "All of the other cat species have lost these specific genes over time, but fishing cats still have them."

This new information about olfactory genes in cats was made possible through a new approach to genome sequencing called trio binning, which allows researchers to sequence the most difficult regions of a genome.

This new technology also makes separating maternal and paternal DNA much easier.

"With trio binning, you can now take DNA from an F1 hybrid -- an animal whose DNA is split 50-50 between parents of different species -- and cleanly separate the maternal and paternal DNA, giving you two complete sets of DNA, one for each parent species," Murphy said. "The process is much simpler, and the results are more complete."

Filling In The Blanks

One of the most important conclusions from the project is that cat species may be similar in many ways, but their differences matter.

"These differences are showing us how these animals are perfectly suited for their natural environments," Murphy said. "They're not interchangeable, and that's valuable information for conservationists and others working to preserve or restore species in their natural habitats.

"For example, you can't assume that tigers from Sumatra and Siberia are the same," he said. "Their environments are wildly different, and those tiger populations have likely developed specialized genetic adaptations to help them survive in these very different places."

It's also important for scientists to realize that the sections of genomes that are the most difficult to assemble may just be the key to understanding crucial bodily systems like immunity and reproduction.

"Olfactory genes aren't the only ones that have been challenging to sequence and study. Scientists have also struggled to sequence immune and reproductive genes, so previous studies are missing this kind of information. Imagine trying to study a genetic condition in cats, humans, or any species, for that matter, without having all the pieces; this is why assembling complete genomes matters," Murphy said.

Read more at Science Daily

Natural GM crops: Grasses take evolutionary shortcut by borrowing genes from their neighbors

Grass may transfer genes from their neighbours in the same way genetically modified crops are made, a new study has revealed.

Research, led by the University of Sheffield, is the first to show the frequency at which grasses incorporate DNA from other species into their genomes through a process known as lateral gene transfer.

The stolen genetic secrets give them an evolutionary advantage by allowing them to grow faster, bigger or stronger and adapt to new environments quicker.

Understanding the rate is important to know the potential impact it can have on a plant's evolution and how it adapts to the environment.

Grasses are the most ecologically and economically important group of plants, covering 30% of the earth's terrestrial surface and producing a majority of our food.

The Sheffield team sequenced multiple genomes of a species of tropical grass and determined at different time points in its evolution how many genes were acquired -- giving a rate of accumulation.

It is now thought these transfers are likely to occur in the same way that some genetically modified crops are made.

These findings, published in the journal New Phytologist could inform future work to harness the process to improve crop productivity and make more resilient crops, and have implications on how we view and use controversial GM crops.

Dr. Luke Dunning, Research Fellow from the University of Sheffield's School of Biosciences, and senior author of the research, said: "There are many methods to make GM crops, some which require substantial human intervention and some that don't. Some of these methods that require minimal human intervention could occur naturally and facilitate the transfers we have observed in wild grasses.

"These methods work by contaminating the reproductive process with DNA from a third individual. Our current working hypothesis, and something we plan to test in the near future, is that these same methods are responsible for the gene transfers we document in wild grasses.

"This means, in the near future, controversial genetic modification could be perceived as more of a natural process.

"Currently, these 'natural' reproductive contamination methods are not as efficient in producing GM plants as those that are used routinely, but by further understanding how lateral gene transfer occurs in the wild we may be able to increase the success of this process."

Since Darwin, much of our understanding of evolution has been based on the assumption that genetic information is passed from parents to offspring -- the rule of common descent for plant and animal evolution.

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Longevity gene from naked mole rats extends lifespan of mice

In a groundbreaking endeavor, researchers at the University of Rochester have successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse's lifespan.

Naked mole rats, known for their long lifespans and exceptional resistance to age-related diseases, have long captured the attention of the scientific community. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the Rochester researchers have opened exciting possibilities for unlocking the secrets of aging and extending human lifespan.

"Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals," says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester. Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4 percent increase in median lifespan for the mice.

A unique mechanism for cancer resistance

Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-size rodents. Unlike many other species, naked mole rats do not often contract diseases -- including neurodegeneration, cardiovascular disease, arthritis, and cancer -- as they age. Gorbunova and Seluanov have devoted decades of research to understanding the unique mechanisms that naked mole rats use to protect themselves against aging and diseases.

The researchers previously discovered that HMW-HA is one mechanism responsible for naked mole rats' unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumors.

Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals.

Transferring a gene that produces HMW-HA

The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression.

The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies -- inflammation being a hallmark of aging -- and maintained a healthier gut.

While more research is needed on exactly why HMW-HA has such beneficial effects, the researchers believe it is due to HMW-HA's ability to directly regulate the immune system.

A fountain of youth for humans?

The findings open new possibilities for exploring how HMW-HA could also be used to improve lifespan and reduce inflammation-related diseases in humans.

"It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice," Gorbunova says. "Our next goal is to transfer this benefit to humans."

They believe they can accomplish this through two routes: either by slowing down degradation of HMW-HA or by enhancing HMW-HA synthesis.

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Researchers identify 135 new melanin genes responsible for pigmentation

The skin, hair and eye color of more than eight billion humans is determined by the light-absorbing pigment known as melanin. An article recently published in the journal Science features research from Vivek Bajpai, Ph.D., lead author and an assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering at the University of Oklahoma, and collaborators from Stanford University. Their research has identified 135 new genes associated with pigmentation.

Melanin is produced within special structures called melanosomes. Melanosomes are found inside melanin-producing pigment cells called melanocytes. Although all humans have the same number of melanocytes, the amount of melanin they produce differs and gives rise to the variation in human skin color.

"To understand what actually causes different amounts of melanin to be produced, we used a technology called CRISPR-Cas9 to genetically engineer cells," Bajpai said. "Using CRISPR, we systematically removed more than 20,000 genes from hundreds of millions of melanocytes and observed the impact on melanin production."

To identify which genes influence melanin production, cells that lost melanin during the gene removal process needed to be separated from millions of other cells that did not. Using in vitro cell cultures, Bajpai developed a novel method to achieve this goal that detects and quantifies the melanin-producing activity of melanocytes. By passing light through the melanocytes, he could record if the light was either absorbed or scattered by the melanin inside.

"If there are a lot of melanin-producing melanosomes, the light will scatter much more than in cells with little melanin," Bajpai said. "Using a process called side-scatter of flow cytometry, we were able to separate cells with more or less melanin. These separated cells were then analyzed to determine the identity of melanin-modifying genes. We identified both new and previously known genes that play important roles in regulating melanin production in humans."

The researchers found 169 functionally diverse genes that impacted melanin production. Of those, 135 were not previously associated with pigmentation. They further identified the function of two newly discovered genes: KLF6 and COMMD3. The DNA-binding protein KLF6 led to a loss of melanin production in humans and animals, confirming the role KLF6 plays in melanin production in other species as well. The COMMD3 protein regulated melanin synthesis by controlling the acidity of melanosomes.

Historically, darker pigmentation has been needed to protect against ultraviolet radiation in areas closer to the equator and for people who spend hours in direct sunlight. As humans moved into areas with less direct sunlight or fewer hours of daylight overall, less melanin was needed. Over time, this resulted in melanosomes that produced less melanin, thus absorbing more sunlight.

"By understanding what regulates melanin, we can help protect lighter-skinned people from melanoma, or skin cancer," Bajpai said. "By targeting these new melanin genes, we could also develop melanin-modifying drugs for vitiligo and other pigmentation diseases."

The technological processes developed and used by the research team could also be applied to identify genes that regulate melanin production in fungi and bacteria. Melanin production in fungi and bacteria enables them to be more pathogenic to humans or crops. Researchers could develop effective interventions against these microbes and their diseases by discovering and targeting such melanin-producing genes.

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Scientists uncover a startling -- and exploitable -- coordination of gene expression in tumors

A Ludwig Cancer Research study has identified a pair of genes whose expression by a type of immune cell within tumors is predictive of outcomes for cancer patients and is linked to a vast network of gene expression programs, engaged by multiple cell types in the tumor microenvironment, that control human cancers.

Researchers led by Ludwig Lausanne's Mikaël Pittet report in the current issue of Science that patients with higher expression of the gene CXCL9 in their tumor-associated macrophages had far better clinical outcomes than those with higher expression of a gene named SPP1 by the immune cells. Macrophages expressing the former gene, they show, are invariably poised to attack cancer cells, while those expressing SPP1 are in a state supportive of tumor growth. Most intriguing, however, is the discovery that when the ratio of CXCL9 to SPP1 is high in the tumor microenvironment (TME), gene expression programs in other TME cells indicate a similarly anti-tumor slant; a low CS ratio, on the other hand, invariably accompanies pro-tumor gene expression signatures across the TME.

"We were very surprised to find that just this one parameter -- the ratio of two genes primarily expressed by macrophages -- could tell us so much else about the tumor," said Pittet. "This is true for multiple types of solid tumors. It means that, despite their enormous complexity, the microenvironments of tumors are governed by a clear set of rules. We have described one of them in this study."

With further validation in prospective clinical studies, Pittet noted, the CS ratio could be an easily measured molecular marker of likely patient prognosis and a useful tool for the management of therapy. Beyond that, the networks of linked gene expression signatures across cell types identified by the study expose several potential molecular targets for the development of drugs that might tip the TME into a state more susceptible to treatments like immunotherapy.

Noncancerous cells of the TME play a critical role in the growth and viability of tumors. These include fibroblasts, which churn out the molecular filler of tissues, endothelial cells that build blood vessels, epithelial cells that line body cavities and a menagerie of immune cell species that variously help or hinder tumor growth. The possibility of targeting these cells to treat cancers is tantalizing because, unlike malignant cells, they do not mutate rapidly and are thus unlikely to evolve resistance to therapies.

Pittet and his colleagues were interested in how much the TME varies between tumors. To find out, they conducted an unbiased analysis of 52 primary and metastatic tumors from 51 patients with head and neck cancers, examining how global gene expression captured in individual cells but statistically analyzed across tumors as a whole corresponded to patient outcomes.

This approach identified CXCL9 and SPP1 -- whose expression is mutually exclusive in individual macrophages -- as being tightly linked to prognosis, and this turned out to be true for other solid cancers as well. The expression of the two genes, Pittet and colleagues show, is also more categorically associated with the anti-tumor or pro-tumor "polarity" of macrophages than currently used markers.

Notably, the ratio of CXCL9 and SPP1 expression (termed CShi or CSlow) was broadly consistent with the state of other types of TME cells in head and neck tumors and with several phenomena associated with pro- and anti-tumor effects. CShi tumors, for example, tended to be infiltrated with B and T lymphocytes and dendritic cells, which all drive anti-tumor immunity. Further, other cell types in these tumors engaged signaling molecules and pathways that fuel inflammation or otherwise instigate immune responses.

CSlow tumors, meanwhile, bore gene expression signatures associated with cancer growth and progression, such as adaptations to oxygen starvation, the formation of new blood vessels and the induction of cellular transformations that propel cancer metastasis.

"Just by looking at the ratio of these two genes in macrophages, you can deduce the molecular activity of tumor cells, endothelial cells, fibroblasts -- you name it," said Pittet. "This startling coherence means that tumors are not a chaotic place, that all these cell states within the TME are coordinated. This information has the potential to be very useful for the development of precision medicine strategies for cancer therapy."

Pittet and his colleagues will next examine whether the gene expression networks identified in their study can be used to prospectively predict patient outcomes or gauge likely responses to various therapies. They will also be looking in more detail at other coordinated axes of gene expression in the TME, how they interact with the CS ratio and how each influences the other.

"The big question is, what are the best ways to interfere therapeutically with this network, with the goal being benefit to the patient?" said Pittet.

Read more at Science Daily

'Mind controlling' parasitic worms are missing genes found in every other animal

In a world full of bizarre animals, hairworms are some of the strangest: parasitic worms that manipulate the behavior of their hosts in what's sometimes called "mind control." A new study in the journal Current Biology reveals another strange trait shared by different hairworm species: they're missing about 30% of the genes that researchers expected them to have. What's more, the missing genes are responsible for the development of cilia, the hair-like structures present in at least some of the cells of every other animal known.

Hairworms are found all over the world, and they look like skinny strands of spaghetti, a couple inches long. Their simple bodies hint at their parasitic lifestyle -- they have no excretory, respiratory, or circulatory systems, and they spend almost their entire lives inside the bodies of other animals. "One of the coolest things, maybe the thing that they are most known for, is that they can affect the behavior of their hosts and make them do things that they wouldn't do otherwise," says Tauana Cunha, a postdoctoral researcher at Chicago's Field Museum and lead author of the study done in collaboration with Harvard University and the University of Copenhagen.

There are a few hundred species of freshwater hairworms. Their eggs hatch in water, and the hairworm larvae get eaten by tiny water-dwelling predators like mayfly larvae, which in turn get eaten by bigger, land-dwelling predators like crickets. After growing into adulthood inside of their new hosts' bodies, the hairworms manipulate the hosts' behavior, causing them to jump into water. There, the worms swim out of their hosts' butts and seek out mates, knotting themselves together, to begin the cycle anew. (There are also five species of hairworms that live in marine environments and parasitize water-dwelling creatures like lobsters, but it's not clear if those ones also have host manipulation capabilities -- there's no pressure for the worms to get back to the water, since the hosts already live there.)

As strange as hairworms' behavior is, Cunha's research interest in the animals has more to do with their DNA. "We set out to sequence their genomes, because nothing like them has ever been sequenced before at that level," she says of the study conducted with her co-authors Bruno de Medeiros, Arianna Lord, Martin Sørensen, and Gonzalo Giribet. "The goal was to produce those genomes and eventually use them to understand the evolutionary relationships between hairworms and other kinds of animals."

She and her colleagues took DNA samples from two hairworm species -- one freshwater and one saltwater -- and sequenced them. But when they compared the hairworms' genetic codes to those of other animals, they found something striking.

"What we found, which was very surprising, was that both hairworm genomes were missing about 30% of a set of genes that are expected to be present across basically all groups of animals," says Cunha.

Results like that often make scientists wonder if they've made a mistake. But there was a connection between the missing genes in the two worm species. "The large majority of the missing genes were exactly the same between the two species. This was just implausible by chance," says Cunha.

By looking at what functions these missing genes are responsible for in other animal groups, Cunha and colleagues showed that they give the instructions for producing cilia. "Cilia are organelles, small structures at the cellular level, that are basically present across all animals and even more broadly, in protists and some plants and fungi. So they're present across a large diversity of life on Earth," says Cunha. They're present in many of the cells in the human body: for instance, the tails of sperm cells are cilia, and cells in the retinas of our eyes have cilia too.

Previously, scientists had found that hairworms seemed to be missing cilia where they'd normally be found. Hairworm sperm, for example, do not have tails. But while no one had ever seen a ciliated cell from a hairworm, that wasn't considered definitive proof that they didn't have them. It's hard to prove something with negative evidence. "Without the genomes, this would require looking at all cells in all life stages in all species," says Bruno de Medeiros, Curator of Pollinating Insects at the Field Museum and co-author of the paper.

"Based on previous observations, it didn't seem like hairworms had any cilia, but we didn't really know for sure," says Cunha. "Now with the genomes, we saw that they actually lack the genes that produce cilia in other animals -- they don't have the machinery to make cilia in the first place."

What's more, the fact that both the freshwater and marine hairworm species had lost the genes for cilia indicates that this evolutionary change happened in the deep past to the two species' common ancestor. "It is likely that the loss happened early on in the evolution of the group, and they just have been carrying on like that," says Cunha.

The finding opens the door to several new questions. It's not clear how the lack of cilia have affected hairworms, or if the hairworms' parasitic behavior could be related to the missing cilia. "There are plenty of other parasitic organisms that aren't missing these specific genes, so we cannot say that the genes are missing because of their parasitic lifestyle," says Cunha. "But parasitic organisms in general are often missing lots of genes. It's hypothesized that because parasites are not using certain structures and instead rely on their hosts, they end up losing those structures."

Read more at Science Daily

Genes for learning and memory are 650 million years old

A team of scientists led by researchers from the University of Leicester have discovered that the genes required for learning, memory, aggression and other complex behaviours originated around 650 million years ago.

The findings led by Dr Roberto Feuda, from the Neurogenetic group in the Department of Genetics and Genome Biology and other colleagues from the University of Leicester and the University of Fribourg (Switzerland), have now been published in Nature Communications.

Dr Feuda said: "We've known for a long time that monoamines like serotonin, dopamine and adrenaline act as neuromodulators in the nervous system, playing a role in complex behaviour and functions like learning and memory, as well as processes such as sleep and feeding.

"However, less certain was the origin of the genes required for the production, detection, and degradation of these monoamines. Using the computational methods, we reconstructed the evolutionary history of these genes and show that most of the genes involved in monoamine production, modulation, and reception originated in the bilaterian stem group.

"This finding has profound implications on the evolutionary origin of complex behaviours such as those modulated by monoamines we observe in humans and other animals."

The authors suggest that this new way to modulate neuronal circuits might have played a role in the Cambrian Explosion -- known as the Big Bang -- which gave rise to the largest diversification of life for most major animal groups alive today by providing flexibility of the neural circuits to facilitate the interaction with the environment.

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Sociogenomics: The intricate science of how genetics influences sociology

Humans contain multitudes. Each person on the planet contains enough DNA to stretch to Pluto -- several times.

Studying how all this genetic material works, and especially how genes influence human behavior, is an enormously complicated undertaking -- one that's being made easier by the emergence of massive banks of genetic data and complex data science analysis techniques to parse that data.

Robbee Wedow, an assistant professor of sociology and data science in Purdue University's College of Liberal Arts, an adjunct assistant professor of medical and molecular genetics in the Indiana University School of Medicine, and Purdue's inaugural faculty-in-residence at AnalytiXIN/16 Tech in Indianapolis, maps those miles of genes for insights into how genetics interacts with social forces and environments. He uses genetic databases to study how tiny bits of genes called single nucleotide polymorphisms, or SNPs, affect complex, overarching traits including sexual behavior, educational attainment, socioeconomic status, health behaviors and more.

"We know that social forces like socioeconomic status play a role in influencing a person's life and life outcomes," Wedow said. "But we also know there is a genetic component to every behavior. What we don't understand yet is how these biological forces interact with the environment and what these sorts of interactions might mean for social science -- and what we think we know about social science research to date. We are using well-powered genetic data to do more accurate and replicable social science and to explore what might be possible at the intersection of genetic and behavioral science."

When scientists sequenced the first human genome in 2003, the true scale of genetics started to become apparent. Early geneticists thought that finding a gene for each trait was simply a matter of looking in the right place.

However, DNA bases and genes are not simply keys on a massive piano upon which human lives are played like masterpieces. Instead, DNA operates more like a pipe organ, where stops, switches and pedals can change the way notes sound, mute them or increase their volume. Environment, nutrition, pollution, life experiences and other circumstances can change when and how genes matter for certain outcomes, and even change which places in the genomes matter for those outcomes altogether. There isn't a single gene for a behavioral outcome. Biology isn't destiny: It may lay out the musical score, but musicians are free to improvise and interpret as they play.

The idea, Wedow stresses, is not that these genes control a person's life or destiny. Each SNP, in fact, has a very small effect on an overall outcome like educational attainment. No "Gattaca"-level reading of one's destiny from their genes -- in the style of the dystopian 1990s movie -- is on the horizon. Rather, being able to clarify the genetics of certain behaviors can help scientists understand the nuances of human behavior.

"People think that genetics is always about biology, but in the case of sociogenomics it's more about using the advantages of this new, well-powered data to better understand the outcomes themselves, or about allowing researchers to do more accurate social science and behavioral research," Wedow said. "The social sciences have recently struggled with replicating studies. Oftentimes the sample sizes are too small for rigorous estimates and certainty. That's where the potential of using these huge banks of genetic data for the social sciences comes in. They help us get a much clearer, more certain look at what's really going on."

Analyzing the genetics is only the first step. An American geneticist in the early 1800s could have correlated genetics with educational mastery and concluded that anyone with two X chromosomes tended to have less education. That is not because the chromosomes had anything at all to do with education. Rather, the correlation reflected social and gender biases present in the culture at the time. Similar insights lurk in Wedow's research.

"Sociogenomics isn't necessarily about biology, like some might think," Wedow said. "When someone studies cancer genetics, they are studying it because they want to elucidate the biology of cancer; they want to figure out ways to better diagnose it, track it and treat it. But researchers in the field of sociogenomics want to study the genetics in order to do better social science. No one would ever study sociology without considering socioeconomic status and environment. We want to be able to take genetics into account in the same way."

In a study in volume 7, No. 7 of the journal Nature Human Behaviour, Wedow, his co-corresponding author Andrea Ganna from the University of Helsinki, and his other co-authors looked at 109 survey questions in over 300,000 individuals to examine the ways that people's genes correlated with whether they answered certain questions or left them blank in surveys answered in the UK Biobank. That may sound fairly abstruse, but it fills a gap that the field of sociology has struggled with for decades.

"How do you know what you don't know or how someone might have answered a question if they choose not to answer it?" Wedow said. "It turns out that the genetics of people who either answer the survey question, or do not, overlaps with the genetics of other outcomes like education, income or certain health behaviors."

That means that scientists can use this type of data to get a better understanding of how people who choose not to answer questionnaires might also share similar responses to questions about health or social behaviors. Geneticists can also use the results of this study to correct for bias in genetic studies of any behavioral, psychiatric or medical outcomes.

Read more at Science Daily

Focus on function helps identify the changes that made us human

Humans split away from our closest animal relatives, chimpanzees, and formed our own branch on the evolutionary tree about seven million years ago. In the time since -- brief, from an evolutionary perspective -- our ancestors evolved the traits that make us human, including a much bigger brain than chimpanzees and bodies that are better suited to walking on two feet. These physical differences are underpinned by subtle changes at the level of our DNA. However, it can be hard to tell which of the many small genetic differences between us and chimps have been significant to our evolution.

New research from Whitehead Institute Member Jonathan Weissman; University of California, San Francisco Assistant Professor Alex Pollen; Weissman lab postdoc Richard She; Pollen lab graduate student Tyler Fair; and colleagues uses cutting edge tools developed in the Weissman lab to narrow in on the key differences in how humans and chimps rely on certain genes. Their findings, published in the journal Cell on June 20th, may provide unique clues into how humans and chimps have evolved, including how humans became able to grow comparatively large brains.

Studying function rather than genetic code

Only a handful of genes are fundamentally different between humans and chimps; the rest of the two species' genes are typically nearly identical. Differences between the species often come down to when and how cells use those nearly identical genes. However, only some of the many differences in gene use between the two species underlie big changes in physical traits. The researchers developed an approach to narrow in on these impactful differences.

Their approach, using stem cells derived from human and chimp skin samples, relies on a tool called CRISPR interference (CRISPRi) that Weissman's lab developed. CRISPRi uses a modified version of the CRISPR/Cas9 gene editing system to effectively turn off individual genes. The researchers used CRISPRi to turn off each gene one at a time in a group of human stem cells and a group of chimp stem cells. Then they looked to see whether or not the cells multiplied at their normal rate. If the cells stopped multiplying as quickly or stopped altogether, then the gene that had been turned off was considered essential: a gene that the cells need to be active-producing a protein product-in order to thrive. The researchers looked for instances in which a gene was essential in one species but not the other as a way of exploring if and how there were fundamental differences in the basic ways that human and chimp cells function.

By looking for differences in how cells function with particular genes disabled, rather than looking at differences in the DNA sequence or expression of genes, the approach ignores differences that do not appear to impact cells. If a difference in gene use between species has a large, measurable effect at the level of the cell, this likely reflects a meaningful difference between the species at a larger physical scale, and so the genes identified in this way are likely to be relevant to the distinguishing features that have emerged over human and chimp evolution.

"The problem with looking at expression changes or changes in DNA sequences is that there are many of them and their functional importance is unclear," says Weissman, who is also a professor of biology at the Massachusetts Institute of Technology and an Investigator with the Howard Hughes Medical Institute. "This approach looks at changes in how genes interact to perform key biological processes, and what we see by doing that is that, even on the short timescale of human evolution, there has been fundamental rewiring of cells."

After the CRISPRi experiments were completed, She compiled a list of the genes that appeared to be essential in one species but not the other. Then he looked for patterns. Many of the 75 genes identified by the experiments clustered together in the same pathways, meaning the clusters were involved in the same biological processes. This is what the researchers hoped to see. Individual small changes in gene use may not have much of an effect, but when those changes accumulate in the same biological pathway or process, collectively they can cause a substantive change in the species. When the researchers' approach identified genes that cluster in the same processes, this suggested to them that their approach had worked and that the genes were likely involved in human and chimp evolution.

"Isolating the genetic changes that made us human has been compared to searching for needles in a haystack because there are millions of genetic differences, and most are likely to have negligible effects on traits," Pollen says. "However, we know that there are lots of small effect mutations that in aggregate may account for many species differences. This new approach allows us to study these aggregate effects, enabling us to weigh the impact of the haystack on cellular functions."

Researchers think bigger brains may rely on genes regulating how quickly cells divide

One cluster on the list stood out to the researchers: a group of genes essential to chimps, but not to humans, that help to control the cell cycle, which regulates when and how cells decide to divide. Cell cycle regulation has long been hypothesized to play a role in the evolution of humans' large brains. The hypothesis goes like this: Neural progenitors are the cells that will become neurons and other brain cells. Before becoming mature brain cells, neural progenitors divide multiple times to make more of themselves. The more divisions that the neural progenitors undergo, the more cells the brain will ultimately contain -- and so, the bigger it will be. Researchers think that something changed during human evolution to allow neural progenitors to spend less time in a non-dividing phase of the cell cycle and transition more quickly towards division. This simple difference would lead to additional divisions, each of which could essentially double the final number of brain cells.

Consistent with the popular hypothesis that human neural progenitors may undergo more divisions, resulting in a larger brain, the researchers found that several genes that help cells to transition more quickly through the cell cycle are essential in chimp neural progenitor cells but not in human cells. When chimp neural progenitor cells lose these genes, they linger in a non-dividing phase, but when human cells lose them, they keep cycling and dividing. These findings suggest that human neural progenitors may be better able to withstand stresses -- such as the loss of cell cycle genes -- that would limit the number of divisions the cells undergo, enabling humans to produce enough cells to build a larger brain.

"This hypothesis has been around for a long time, and I think our study is among the first to show that there is in fact a species difference in how the cell cycle is regulated in neural progenitors," She says. "We had no idea going in which genes our approach would highlight, and it was really exciting when we saw that one of our strongest findings matched and expanded on this existing hypothesis."

More subjects lead to more robust results

Research comparing chimps to humans often uses samples from only one or two individuals from each species, but this study used samples from six humans and six chimps. By making sure that the patterns they observed were consistent across multiple individuals of each species, the researchers could avoid mistaking the naturally occurring genetic variation between individuals as representative of the whole species. This allowed them to be confident that the differences they identified were truly differences between species.

The researchers also compared their findings for chimps and humans to orangutans, which split from the other species earlier in our shared evolutionary history. This allowed them to figure out where on the evolutionary tree a change in gene use most likely occurred. If a gene is essential in both chimps and orangutans, then it was likely essential in the shared ancestor of all three species; it's more likely for a particular difference to have evolved once, in a common ancestor, than to have evolved independently multiple times. If the same gene is no longer essential in humans, then its role most likely shifted after humans split from chimps. Using this system, the researchers showed that the changes in cell cycle regulation occurred during human evolution, consistent with the proposal that they contributed to the expansion of the brain in humans.

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Lingering effects of Neanderthal DNA found in modern humans

Recent scientific discoveries have shown that Neanderthal genes comprise some 1 to 4% of the genome of present-day humans whose ancestors migrated out of Africa, but the question remained open on how much those genes are still actively influencing human traits -- until now.

A multi-institution research team including Cornell University has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals that took place some 50,000 years ago. (The study applies only to descendants of those who migrated from Africa before Neanderthals died out, and in particular, those of European ancestry.)

In a study published in eLife, the researchers reported that some Neanderthal genes are responsible for certain traits in modern humans, including several with a significant influence on the immune system. Overall, however, the study shows that modern human genes are winning out over successive generations.

"Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors' migration out of Africa," said study co-lead author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. "We have made our custom software available for free download and use by anyone interested in further research."

Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300,000 Brits of non-African ancestry, the researchers analyzed more than 235,000 genetic variants likely to have originated from Neanderthals. They found that 4,303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person's natural immune resistance to certain diseases.

Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.

While the study used a dataset of almost exclusively white individuals living in the United Kingdom, the new computational methods developed by the team could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans' genetic influences on modern humans.

"For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks," said senior investigator Sriram Sankararaman, an associate professor at the University of California, Los Angeles. "More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences."

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Scales or feathers? It all comes down to a few genes

Scales, spines, feathers and hair are examples of vertebrate skin appendages, which constitute a remarkably diverse group of micro-organs. Despite their natural multitude of forms, these appendages share early developmental processes at the embryonic stage. Two researchers from the University of Geneva (UNIGE) have discovered how to permanently transform the scales that normally cover the feet of chickens into feathers, by specifically modifying the expression of certain genes. These results, published in the journal Science Advances, open new perspectives for studying mechanisms that have enabled radical evolutionary transitions in form among species.

The skin of terrestrial vertebrates is adorned with diverse keratinized appendages, such as hair, feathers, and scales. Despite the diversity of forms within and among species, the embryonic development of skin appendages typically begins in a very similar way. Indeed, all of these structures develop from cells that produce a localized thickening on the skin surface and express particular genes. One of these genes, called Sonic hedgehog (Shh), controls a signaling pathway -- a communication system that allows the transmission of messages within and between cells. Shh signalling is involved in the development of diverse structures, including the neural tube, limb buds and skin appendages.

A common ancestor

The laboratory of Michel Milinkovitch, professor in the Department of Genetics and Evolution at the Faculty of Science of the UNIGE, is interested in the physical and biological processes that generate the diversity of skin appendages in vertebrates. In particular, his group has previously demonstrated that hair, feathers and scales are homologous structures inherited from a reptilian common ancestor.

Feathers of the chicken embryo are used by scientists as a model system to understand skin appendage development. While it is known that certain breeds of chickens, such as the 'Brahma' and 'Sablepoot' varieties, exhibit feathered legs and dorsal foot surfaces, the genetic determinism of this trait is not fully understood.

A transient modification for a permanent change

As the signaling pathways responsible for this transformation have not been fully determined, Michel Milinkovitch's group investigated the potential role of the Shh pathway. "We used the classic technique of 'egg candling', in which a powerful torch illuminates blood vessels on the inside of the eggshell. This allowed us to precisely treat chicken embryos with a molecule that specifically activates the Shh pathway, injected directly into the bloodstream,'' explains Rory Cooper, a post-doctoral researcher in Michel Milinkovitch's laboratory and co-author of the study.

The two scientists observed that this single stage-specific treatment is sufficient to trigger the formation of abundant juvenile down-type feathers, in areas that would normally be covered with scales. Remarkably, these experimentally-induced feathers are comparable to those covering the rest of the body, as they are regenerative and are subsequently and autonomously replaced by adult feathers.

After comparison with embryos injected with a 'control' solution (without the active molecule), RNA sequencing analysis showed that the Shh pathway is both immediately and persistently activated following injection of the molecule. This confirms that activation of the Shh pathway underlies the conversion of scales into feathers.

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