Cracking the code: Genome sequencing reveals why songbirds are larger in colder climates

Scientists have unlocked the genetic basis underlying the remarkable variation in body size observed in song sparrows, one of North America's most familiar and beloved songbirds. This discovery also provides insights into this species' capacity to adapt to the challenges of climate change.

The study, published today in Nature Communications, used genomic sequencing to successfully pinpoint eight genetic variants, or DNA mutations, largely responsible for the nearly threefold difference in body size observed across the song sparrow range from Mexico to Alaska. For instance, song sparrows that live year-round in the Aleutian Islands can be up to three times larger than their counterparts in the coastal marshes of California.

Katherine Carbeck, the study's first author and a PhD candidate in the faculty of forestry, University of British Columbia, explains that body size varies predictably in many species that inhabit vastly different climatic conditions, aligning with "Bergmann's rule" which states that organisms in cooler climates tend to be larger as an adaptation to regulate body temperature.

"The existence of 'locally adapted' populations implies that natural selection has shaped the genetic makeup of song sparrow populations across their range, enabling individuals to survive and reproduce in drastically different climatic conditions," said Carbeck. "However, the genetic mechanisms underlying Bergmann's rule have remained elusive until now."

Whole-genome sequencing cracks the code

Carbeck and colleagues from the Cornell Lab of Ornithology, University of Alaska and Ouachita Baptist University used the power of whole-genome sequencing to decode the entire song sparrow genome and unlock its secrets.

They combed through genetic samples from the two largest song sparrow subspecies that live year-round in the Aleutian Islands, as well as two smaller subspecies: one that breeds in Alaska but migrates to warmer sites in winter, and one that lives year-round on the B.C. coast, where the Pacific Ocean maintains comparatively mild winter weather.

Their comparison of the larger and smaller-bodied subspecies revealed several candidate genes associated with body mass. By characterizing these candidates, they identified eight specific genetic variants closely linked to body mass -- aligning with Bergmann's rule.

Genetic diversity helps life adapt to climate change

The researchers suggest that revealing a genetic basis for Bergmann's rule helps us to understand how evolution, natural selection and climate have interacted throughout a species' history.

"Our results highlight the potential role habitat conservation plays in enabling the continued exchange of genes between populations -- which is important in the face of ongoing change," said Carbeck.

Dr. Jen Walsh, a study co-author and research associate at the Cornell Lab of Ornithology, added: "From a genomic perspective, identifying a small number of candidate genes with an apparently large impact on variation in body size is really interesting. The magnificent range of phenotypic diversity seen in song sparrows suggest they offer exciting opportunities to identify genes underlying a host of well-known and generally accepted eco-geographic rules."

Dr. Peter Arcese, a co-author and a professor in UBC's department of forest and conservation sciences, said the findings suggest a resilient future for these birds.

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

Scientist uncovers roots of antibiotic resistance

Bacteria naturally adapt to various environmental stimuli and as they mutate, these changes can make them resistant to drugs that would kill or slow their growth.

In a recent article published in PLoS Genetics, UCF College of Medicine microbiologist Dr. Salvador Almagro-Moreno uncovers the evolutionary origins of antimicrobial resistance (AMR) in bacteria. His studies on the bacterium that causes cholera, Vibrio cholerae, provide insight into deciphering what conditions must occur for infectious agents to become resistant.

"How AMR occurs in bacterial populations and the pathways leading to these new traits are still poorly understood," he said. "This poses a major public health threat as antimicrobial resistance is on the rise."

Dr. Almagro-Moreno studied genetic variants of a protein found in bacterial membranes called OmpU. Using computational and molecular approaches, his team found that several OmpU mutations in the cholera bacteria led to resistance to numerous antimicrobial agents. This resistance included antimicrobial peptides that act as defenses in the human gut. The researchers found that other OmpU variants did not provide these properties, making the protein an ideal system for deciphering the specific processes that occur to make some bacteria resistant to antimicrobials.

By comparing resistant and antibiotic sensitive variants, the researchers were able to identify specific parts of OmpU associated with the emergence of antibiotic resistance. They also discovered that the genetic material encoding these variants, along with associated traits, can be passed between bacterial cells, increasing therisk of spreading AMR in populations under antibiotic pressure.

By understanding how mutations occur, researchers can better understand and develop therapeutics to combat resistant infections. Dr. Almagro-Moreno is also looking at environmental factors such as pollution and warming of the oceans, as possible causes of resistant bacteria. "We are studying the genetic diversity ofenvironmental populations, including coastal Florida isolates, to develop a new approach to understandinghow antimicrobial resistance evolves," he explained.

Read more at Science Daily

Green tea extract may harm liver in people with certain genetic variations

Long-term use of high-dose green tea extract may provide some protection against cancer, cardiovascular disease, obesity and type 2 diabetes, but it also may create liver damage in a small minority of the population.

Who is at risk? Research from Rutgers, published in The Journal of Dietary Supplements, provides the first solid clue: two genetic variants that predict some of the risk.

"Learning to predict who will suffer liver damage is potentially important because there's growing evidence that high-dose green tea extract may have significant health benefits for those who can safely take it," said Hamed Samavat, senior author of the study and an assistant professor of nutrition sciences at the Rutgers School of Health Professions.

Using data from the Minnesota Green Tea Trial, a large study of green tea's effect on breast cancer, the research team investigated whether people with certain genetic variations were more likely than others to show signs of liver stress after a year of ingesting 843 milligrams per day of the predominant antioxidant in green tea, a catechin called epigallocatechin gallate (EGCG).

Researchers led by Laura Acosta, then a doctoral student, now a graduate, selected two genetic variations in question because each controls the synthesis of an enzyme that breaks EGCG down. They selected the Minnesota Green Tea Trial because it was a large, well-designed study of a unique population. The year-long, placebo-controlled trial included more than 1,000 postmenopausal women and collected data at 3, 6, 9 and 12 months.

An analysis by researchers showed that early signs of liver damage were somewhat more common than normal in women with one variation in the catechol-O-methyltransferase (COMT) genotype and strongly predicted by a variation in the uridine 5'-diphospho-glucuronosyltransferase 1A4 (UGT1A4) genotype.

On average, participants with the high-risk UGT1A4 genotype saw the enzyme that indicates liver stress go up nearly 80 percent after nine months of consuming the green tea supplement, while those with low-risk genotypes saw the same enzyme go up 30 percent.

"We're still a long way from being able to predict who can safely take high-dose green tea extract," said Samavat, who noted the risk of liver toxicity is only associated with high levels of green tea supplements and not with drinking green tea or even taking lower doses of green tea extract. "Variations in this one genotype don't completely explain the variations in liver enzyme changes among study participants. The full explanation probably includes a number of different genetic variations and probably a number of non-genetic factors."

Read more at Science Daily

When did the genetic variations that make us human emerge?

The study of the genomes of our closest relatives, the Neanderthals and Denisovans, has opened up new research paths that can broaden our understanding of the evolutionary history of Homo sapiens. A study led by the University of Barcelona has made an estimation of the time when some of the genetic variants that characterise our species emerged. It does so by analysing mutations that are very frequent in modern human populations, but not in these other species of archaic humans.

The results, published in the journal Scientific Reports, show two moments in which mutations accumulated: one around 40,000 years ago, associated with the growth of the Homo sapiens population and its departure from Africa, and an older one, more than 100,000 years ago, related to the time of the greatest diversity of types of Homo sapiens in Africa.

"The understanding of the deep history of our species is expanding rapidly. However, it is difficult to determine when the genetic variants that distinguish us from other human species emerged. In this study, we have placed species-specific variants on a timeline. We have discovered how these variants accumulate over time, reflecting events such as the point of divergence between Homo sapiens and other human species around 100,000 years ago," says Alejandro Andirkó, first author of this article, which was part of his doctoral thesis at the UB.

The study, led by Cedric Boeckx, ICREA research professor in the section of General Linguistics and member of the Institute of Complex Systems of the UB (UBICS), included the participation of Juan Moriano, UB researcher, Alessandro Vitriolo and Giuseppe Testa, experts from the University of Milan and the European Institute of Oncology, and Martin Kuhlwilm, researcher at the University of Vienna.

Predominance of behavioural and facial-related variations

The results of the research study also show differences between evolutionary periods. Specifically, they highlight the predominance of genetic variants related to behaviour and facial structure -- key characteristics in the differentiation of our species from other human species -- more than 300,000 years ago, a date that coincides with the available fossil and archaeological evidence. "We have discovered sets of genetic variants which affect the evolution of the face and which we have dated between 300,000 and 500,000 years ago, the period just prior to the dating of the earliest fossils of our species, such as the ones discovered at the Jebel Irhoud archaeological site in Morocco," notes Andirkó.

The researchers also analysed variants related to the brain, the organ that can best help explain key features of the rich repertoire of behaviours associated with Homo sapiens. Specifically, they dated variants which medical studies conducted in present-day humans have linked to the volume of the cerebellum, corpus callosum and other structures. "We found that brain tissues have a particular genomic expression profile at different times in our history; that is, certain genes related to neural development were more highly expressed at certain times," says the researcher.

Supporting the mosaic nature of the evolution of Homo sapiens

These results complement an idea that is dominant in evolutionary anthropology: that there is no linear history of human species, but that different branches of our evolutionary tree coexisted and often intersected. "The breadth of the range of human diversity in the past has surprised anthropologists. Even within Homo sapiens there are fossils, such as the ones I mentioned earlier from Jebel Irhoud, which, because of their features, were thought to belong to another species. That's why we say that human beings have lived a mosaic evolution," he notes.

"Our results," the researcher continues, "offer a picture of how our genetics changed, which fits this idea, as we found no evidence of evolutionary changes that depended on one or a several key mutations," he says.

Application of machine learning techniques

The methodology used in the study was based on a Genealogical Estimation of Variant Age method, developed by researchers at the University of Oxford. Once they had this estimation, they applied a machine learning tool to predict which genes have changed the most in certain time windows and which tissues these genes may have impacted. Specifically, they used ExPecto, a deep learning tool that uses a convolutional network -- a type of computational model -- to predict gene expression levels and function from a DNA sequence.

"Since there are no data on the genomic expression of variants in the past, this tool is an approach to a problem that has not been addressed until now. Although the use of machine learning prediction is increasingly common in the clinical world, as far as we know, nobody has tried to predict the consequences of genomic changes over time," notes Andirkó.

The importance of the perinatal phase in the brain development of our species

In a previous study, the same UB team, together with the researcher Raül Gómez Buisán, used genomic information from archaic humans. In that study they analysed genomic deserts, regions of the genome of our species where there are no genetic fragments of Neanderthals or Denisovans, and which, moreover, have been subjected to positive pressure in our species: that is, they have accumulated more mutations than would have been expected by neutral evolution. The researchers studied the expression of genes -- i.e., which proteins code for different functions -- found in desert regions throughout brain development, from prenatal to adult stages, covering sixteen brain structures. The results showed differences in gene expression in the cerebellum, striatum and thalamus. "These results bring into focus the relevance of brain structures beyond the neocortex, which has traditionally dominated research on the evolution of the human brain," says Juan Moriano.

Read more at Science Daily

New sleep molecule discovered: 'It shows just how complex the machinery of sleep is'

Researchers from the University of Copenhagen and Aalborg University presents a new study demonstrating that a small molecule in brain cells affects the level of hypocretin, which is responsible for making us feel awake during the day and tired at night. People with a genetic variation of this molecule have a higher risk of suffering from daytime sleepiness.

When brain scientist Birgitte Kornum from the Department of Neuroscience recently arrived in Rome for one of the largest sleep conferences in the world, she was completely taken aback. There were pharmaceutical companies everywhere -- with stands, information material and campaigns.

They all wanted to treat daytime sleepiness or to turn off the brain at night. And a lot of them focussed on hypocretin, which is a protein found in brain cells and which has recently attracted a lot of attention within sleep research.

This is because hypocretin is suspected to play a role in both insomnia, which is a decreased ability to fall asleep at night, and in narcolepsy, which is a decreased ability to stay awake during the day. People suffering from insomnia may have too much hypocretin in the brain, while people suffering from narcolepsy have too little. Researchers also suspect hypocretin to play a role in depression, ADHD and other mental disorders.

A lot is already known about the hypocretin system in the brain. There is even a new drug for insomnia countering the effect of hypocretin, latest introduced in Canada in 2018. According to Birgitte Kornum, though, the problem is that we know very little about how hypocretin is regulated inside the cells.

Therefore, Associate Professor Birgitte Kornum and her colleagues set out to shed light on the issue in a new study, which has recently been published in the reputed journal PNAS. The study combines tests on mice, zebrafish and human cells, and the researchers cooperated with their neighbours at the University of Copenhagen's Department of Cellular and Molecular Medicine, among others.

MicroRNA associated with sleep regulation

The team of researchers have spent several years studying one of the cellular mechanisms that affect hypocretin levels. Here they have focussed on a small molecule called microRNA-137 (miR-137).

"We discovered that miR-137 helps regulate hypocretin. To experience normal sleep, you need to have the right amount of hypocretin in the brain at the right time, and miR-137 helps with that. Though MiR-137 is also found in other parts of the body, it is especially pronounced in the brain," Birgitte Kornum says about the new study, which she has headed together with Assistant Professor Anja Holm from Aalborg University.

MicroRNA regulates various cellular processes, including hypocretin levels. Therefore, there is considerable research interest in microRNAs, as they could be targeted in order to regulate such processes.

Previously, the scientists knew very little about the role played by miR-137 in the brain, but now Birgitte Kornum's research team has demonstrated that it is associated with hypocretin regulation and thus with sleep.

"This is the first time a microRNA is associated with sleep regulation. Drawing on the UK Biobank, we discovered some genetic mutations in miR-137 which cause daytime sleepiness. The study demonstrates this connection in both mice and zebrafish, and we are able to prove the connection with hypocretin. Our discovery shows just how complex the machinery of sleep is. Imagine inheriting a variant of miR-137 that puts you at higher risk of feeling sleepy during the day," says Birgitte Kornum.

Hypocretin affects sleep stages

Hypocretin, which has caught the attention of the pharmaceutical companies, also affects the order of the sleep stages.

Our sleep is usually divided into four stages. The stages follow a specific order, and this order is vital to the quality of our sleep.

"Narcolepsy patients suffering from low levels of hypocretin experience muddled sleep stages. We know this from mice tests demonstrating that hypocretin affects the order of these stages," explains Anja Holm from Aalborg University, who is first author of the study and who did the tests together with Birgitte Kornum.

Existing research suggests that to solve the problem we need to gain more knowledge of hypocretin regulation. And here the Danish researchers point to a different, but equally important piece of the puzzle, namely the immune system.

"Most people know that when you are ill you often feel tired. And when you have a fever and the immune system is hard at work, you often suffer from poor sleep. So we know that something happens to the hypocretin level when the body is trying to fight off a virus infection, for example, and we are trying to understand this process," says Birgitte Kornum.

Read more at Science Daily