How selfish genes succeed

New findings from the Stowers Institute for Medical Research uncover critical insights about how a dangerous selfish gene -- considered to be a parasitic portion of DNA -- functions and survives. Understanding this dynamic is a valuable resource for the broader community studying meiotic drive systems.

A new study, published in PLoS Genetics on Dec. 7, 2022, reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are designing synthetic drive systems for pathogenic pest control. Collective and collaborative advancement on understanding drive may one day lead to the eradication of pest populations that harm crops or even humans in the case of vector borne diseases.

"It's quite dangerous for a genome to encode a protein that has the capacity to kill the organism," said Stowers Associate Investigator SaraH Zanders, Ph.D. "However, understanding the biology of these selfish elements could help us build synthetic drivers to modify natural populations."

Drivers are selfish genes that can spread in a population at higher rates than most other genes, without benefiting the organism. Previous research from the Zanders Lab revealed that a driver gene in yeast, wtf4, produces poison protein capable of destroying all offspring. However, for a given parent cell's chromosome pair, drive is achieved when wtf4 is found only on one chromosome. The effect is a simultaneous rescue of only those offspring that inherit the drive allele, by delivering a dose of a very similar protein that counteracts the poison, the antidote.

Building upon this work, the study, led by former Predoctoral Researcher Nicole Nuckolls, Ph.D., and current Predoctoral Researcher Ananya Nidamangala Srinivasa in the Zanders Lab, discovered that differences in the timing of generating poison and antidote proteins from wtf4 and their unique distribution patterns within developing spores are fundamental to the drive process.

The team has developed a model they are continuing to investigate for how the poison acts to kill the spore -- the equivalent of a human egg or sperm in yeast. Their results indicate that poison proteins cluster together, potentially disrupting proper folding of other proteins required for the cell to function. Because the wtf4 gene encodes both poison and antidote, the antidote is very similar in form and groups together with the poison. However, the antidote has an extra part that appears to isolate the poison-antidote clusters by bringing them to the cell's garbage can, the vacuole.

To understand how selfish genes function during reproduction, the researchers looked at the beginning of spore formation and found poison protein expressed within all developing spores and the sac surrounding them, while the antidote protein was only seen in low concentration throughout the sac. Later in development, the antidote was enriched inside of the spores that inherited wtf4 from the parent yeast cell.

The researchers found that spores that inherited the driver gene manufactured additional antidote protein inside the spore to neutralize the poison and ensure their survival.

The team also discovered that a particular molecular switch that controls many other genes involved in spore formation also controls the expression of poison, but not antidote, from the wtf4 gene. The switch is essential for yeast reproduction and is inextricably linked to wtf4, helping to explain why this selfish gene is so successful at evading any attempts by the host to disable the switch.

"One of the reasons we are thinking these things have stuck around for so long -- they've used this sneaky strategy of exploiting the same essential switch that turns on yeast reproduction," said Nidamangala Srinivasa.

"If we could manipulate these DNA parasites to be expressed in mosquitoes and drive their destruction, it may be a way to control pest species," said Nuckolls.

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Sleepless and selfish: Lack of sleep makes us less generous

Humans help each other -- it's one of the foundations of civilized society. But a new study by scientists at the University of California, Berkeley, reveals that a lack of sleep blunts this fundamental human attribute, with real-world consequences.

Lack of sleep is known to be associated with an increased risk of cardiovascular disease, depression, diabetes, hypertension and overall mortality. However, these new discoveries show that a lack of sleep also impairs our basic social conscience, making us withdraw our desire and willingness to help other people.

In one portion of the new study, the scientists showed that charitable giving in the week after the beginning of Daylight Saving Time, when residents of most states "spring forward" and lose one hour of their day, dropped by 10% -- a decrease not seen in states that do not change their clocks or when states return to standard time in the fall.

The study, led by UC Berkeley research scientist Eti Ben Simon and Matthew Walker, a UC Berkeley professor of psychology, adds to a growing body of evidence demonstrating that inadequate sleep not only harms the mental and physical well-being of an individual, but also compromises the bonds between individuals -- and even the altruistic sentiment of an entire nation.

"Over the past 20 years, we have discovered a very intimate link between our sleep health and our mental health. Indeed, we've not been able to discover a single major psychiatric condition in which sleep is normal," Walker said. "But this new work demonstrates that a lack of sleep not only damages the health of an individual, but degrades social interactions between individuals and, furthermore, degrades the very fabric of human society itself. How we operate as a social species -- and we are a social species -- seems profoundly dependent on how much sleep we are getting."

"We're starting to see more and more studies, including this one, where the effects of sleep loss don't just stop at the individual, but propagate to those around us," said Ben Simon. "If you're not getting enough sleep, it doesn't just hurt your own well-being, it hurts the well-being of your entire social circle, including strangers."

Ben Simon, Walker and colleagues Raphael Vallat and Aubrey Rossi will publish their results August 23 in the open access journal PLOS Biology. Walker is the director of the Center for Human Sleep Science. He and Ben Simon are members of the Helen Wills Neuroscience Institute at UC Berkeley.

Sleeplessness dampens theory of mind network

The new report describes three separate studies that assessed the impact of sleep loss on people's willingness to help others. In the first study, the scientists placed 24 healthy volunteers in a functional magnetic resonance imager (fMRI) to scan their brains after eight hours of sleep and after a night of no sleep. They found that areas of the brain that form the theory of mind network, which is engaged when people empathize with others or try to understand other people's wants and needs, were less active after a sleepless night.

"When we think about other people, this network engages and allows us to comprehend what other person's needs are: What are they thinking about? Are they in pain? Do they need help?" Ben Simon said. "However, this network was markedly impaired when individuals were sleep deprived. It's as though these parts of the brain fail to respond when we are trying to interact with other people after not getting enough sleep."

In a second study, they tracked more than 100 people online over three or four nights. During this time, the researchers measured the quality of their sleep -- how long they slept, how many times they woke up -- and then assessed their desire to help others, such as holding an elevator door open for someone else, volunteering or helping an injured stranger on the street.

"Here, we found that a decrease in the quality of someone's sleep from one night to the next predicted a significant decrease in the desire to help other people from one subsequent day to the next," Ben Simon said. "Those with poor sleep the night prior were the ones that reported being less willing and keen to help others the following day."

The third part of the study involved mining a database of 3 million charitable donations in the United States between 2001 and 2016. Did the number of donations change after the transition to Daylight Saving Time and the potential loss of an hour of sleep? They found a 10% drop in donations. This same dent in compassionate gift-giving was not seen in regions of the country that did not change their clocks.

"Even a very modest 'dose' of sleep deprivation -- here, just the loss of one single hour of sleep opportunity linked to daylight saving time -- has a very measurable and very real impact on people's generosity and, therefore, how we function as a connected society," Walker said. "When people lose one hour of sleep, there's a clear hit on our innate human kindness and our motivation to help other people in need."

An earlier study by Walker and Ben Simon showed that sleep deprivation forced people to socially withdraw and become more socially isolated. A lack of sleep also increased their feelings of loneliness. Worse still, when those sleep-deprived individuals interacted with other people, they spread their loneliness to those other individuals, almost like a virus, Walker said.

"Looking at the big picture, we're starting to see that a lack of sleep results in a quite asocial and, from a helping perspective, anti-social individual, which has manifold consequences to how we live together as a social species," he said. "A lack of sleep makes people less empathetic, less generous, more socially withdrawn, and it's infectious -- there is contagion of loneliness."

"The realization that the quantity and quality of sleep affects an entire society, caused by an impairment in prosocial behavior, may provide insights into our societal state of affairs in the present day," Walker added.

This finding also offers a novel approach to improving these specific aspects of our society.

"Promoting sleep, rather than shaming people for sleeping enough, could very palpably help shape the social bonds we all experience every day," Ben Simon said.

"Sleep, it turns out, is an incredible lubricant to prosocial, connected, empathic, kind and generous human behavior. In these divisive times, if there was ever a need for a strong, prosocial lubricant to enable the very best version of ourselves within society, now seems to be it," said Walker, author of the international bestseller, Why We Sleep. "Sleep may be a wonderful ingredient that enables the alacrity of helping between human beings."

"Sleep is essential for all aspects of our physical, mental and emotional lives," Ben Simon said. "When sleep is undervalued in society, not only do we get sleep-deprived doctors, nurses and students, but we also suffer from unkind and less empathic interactions on a daily basis."

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Mindfulness can make you selfish

 Mindfulness is big business. Downloads of mindfulness apps generate billions of dollars annually in the U.S., and their popularity continues to rise. In addition to what individual practitioners might have on their phones, schools and prisons along with 1 in 5 employers currently offer some form of mindfulness training.

Mindfulness and meditation are associated with reducing stress and anxiety, while increasing emotional well-being. Plenty of scholarship supports these benefits. But how does mindfulness affect the range of human behaviors -- so-called prosocial behaviors -- that can potentially help or benefit other people? What happens when the research looks outwardly at social effects of mindfulness rather than inwardly at its personal effects?

It's within the area of prosocial behaviors that a new paper by University at Buffalo researchers demonstrates the surprising downsides of mindfulness, while offering easy ways to minimize those consequences -- both of which have practical implications for mindfulness training.

"Mindfulness can make you selfish," says Michael Poulin, PhD, an associate professor of psychology in the UB College of Arts and Sciences and the paper's lead author. "It's a qualified fact, but it's also accurate.

"Mindfulness increased prosocial actions for people who tend to view themselves as more interdependent. However, for people who tend to view themselves as more independent, mindfulness actually decreased prosocial behavior."

The results sound contradictory given the pop culture toehold of mindfulness as an unequivocal positive mental state. But the message here isn't one that dismantles the effectiveness of mindfulness.

"That would be an oversimplification," says Poulin, an expert in stress, coping and prosocial engagement. "Research suggests that mindfulness works, but this study shows that it's a tool, not a prescription, which requires more than a plug-and-play approach if practitioners are to avoid its potential pitfalls."

The findings will appear in a forthcoming issue of the journal Psychological Science.

Poulin says independent versus interdependent mindsets represent an overarching theme in social psychology. Some people think of themselves in singular or independent terms: "I do this." While others think of themselves in plural or interdependent terms: "We do this."

There are also cultural differences layered on top of these perspectives. People in Western nations most often think of themselves as independent, whereas people in East Asian countries more often think of themselves as interdependent. Mindfulness practices originated in East Asian countries, and Poulin speculates that mindfulness may be more clearly prosocial in those contexts. Practicing mindfulness in Western countries removes that context.

"Despite these individual and cultural differences, there is also variability within each person, and any individual at different points in time can think of themselves either way, in singular or plural terms," says Poulin.

The researchers, which included Shira Gabriel, PhD, a UB associate professor of psychology, C. Dale Morrison and Esha Naidu, both UB graduate students, and Lauren M. Ministero, PhD, a UB graduate student at the time of the research who is now a senior behavioral scientist at the MITRE Corporation, used a two-experiment series for their study.

First, they measured 366 participants' characteristic levels of independence versus interdependence, before providing mindfulness instruction or a mind wandering exercise to the control group. Before leaving, participants were told about volunteer opportunities stuffing envelopes for a charitable organization.

In this experiment, mindfulness led to decreased prosocial behavior among those who tended to be independent.

In the next experiment, instead of having a trait simply measured, 325 participants were encouraged to lean one way or the other by engaging in a brief but effective exercise that tends to make people think of themselves in independent or interdependent terms.

The mindfulness training and control procedures were the same as the first experiment, but in this case, participants afterwards were asked if they would sign up to chat online with potential donors to help raise money for a charitable organization.

Mindfulness made those primed for independence 33% less likely to volunteer, but it led to a 40% increase in the likelihood of volunteering to the same organization among those primed for interdependence. The results suggest that pairing mindfulness with instructions explaining how to make people think of themselves in terms of their relationships and communities as they're engaging in mindfulness exercises may allow them to see both positive personal and social outcomes.

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