Introns Nonsense DNA May Be More Important to Evolution of Genomes Than Thought

The sequences of nonsense DNA that interrupt genes could be far more important to the evolution of genomes than previously thought, according to a recent Sciencereport by Indiana University Bloomington and University of New Hampshire biologists.

Their study of the model organismDaphnia pulex (water flea) is the first to demonstrate the colonization of a single lineage by "introns," as the interrupting sequences are known. The scientists say introns are inserted into the genome far more frequently than current models predict. The scientists also found what appear to be "hot spots" for intron insertion -- areas of the genome where repeated insertions are more likely to occur. And surprisingly, the vast majority of intron DNA sequences the scientists examined were of unknown origin.

"The thinking has been that these insertion events are very rare because they always have bad effects," said postdoctoral fellow Abraham Tucker, a lead author of the Science paper.

Graduate student Wenli Li, whose participation in the research overlaps her dissertation work, was the paper's co-lead author. Li said she was particularly interested in the notion of hot spots that make it more likely for separate lineages of Daphnia to gain introns in the same place (or the same general area) within the water fleas' genomes. Four of the 23 different kinds of introns the scientists found were not unique with respect to position. If introns were always inserted in random places within genes, the scientists would have expected zero introns to have identical insertion points.

"The most intriguing finding for me is the multiple instances of parallel intron gains, because this means that Daphnia is in an active phase of intron proliferation," Li said. "This makesDaphnia an extraordinary system to study intron evolution. In addition, we believe our work facilitates a more accurate estimate of intron gain rates, and directly challenges the assumption that parallel intron gains are rare in many prior analyses."

Whether or not Daphnia is typical of eukaryotes with respect to intron gain (and loss), IU Bloomington evolutionary biologist Michael Lynch, the project's principal investigator, agreed that the discovery of parallelism will surprise his colleagues.

"Remarkably, we have found many cases of parallel intron gains at essentially the same sites in independent genotypes," Lynch said. "This strongly argues against the common assumption that when two species share introns at the same site, it is always due to inheritance from a common ancestor."

A unique and important aspect of the scientists' work is that they focused on one species (Daphnia pulex). Past studies have looked at a few introns shared by vastly different species. In doing so, geneticists have almost certainly missed the ephemeral appearance of new introns, and therefore would come to the wrong conclusions about how introns are gained, why they are lost, and how frequently either occurs.

That many introns are not acquired from a common ancestor but are the result of separate insertion events, the scientists say, means that the rates of intron gain in any species' lineage could be considerably higher than currently estimated.

Even if the rates of intron gain and loss of introns in Daphnia pulex are unlike those found in humans, sunflowers, and mushrooms, the Science report suggests geneticists and genome biologists take another look at introns, some of which could have been the result of hot spot insertion events in separate lines.

"The immediate question will be whether our findings can readily be extended to other species," Lynch said. "We are, in fact, doing that now. In addition, there is need for some solid molecular work to test our hypothesis about the mechanism of intron origin."

Intron is short for "intragenic region," a segment of DNA embedded within the coding portion of a gene. Introns are common in eukaryotic organisms -- animals, plants, fungi, and protists. When genes are expressed, special machinery within the cell nucleus usually removes the introns, thereby producing a transcript of the gene that is devoid of nonsense. Some introns are very small (20 DNA base pairs or fewer). A few introns are shockingly long (nearly 500,000 base pairs) long. Within a gene region, the total length of introns may dwarf the actual coding regions. There's a gene on humans' 22nd chromosome that is so riddled with introns, only 10 percent of it actually contains coding DNA. The rest is comprised of introns.

Scientists have generally assumed introns are so deleterious, their insertion almost always spells doom for the cell lines within individual organisms that produce offspring. With the exception of alternative splicing, introns serve no apparent function and consume needless energy when cells must duplicate all of their DNA. More importantly, the insertion of a new intron in a bad place can interfere with the cellular machinery's expression of an important gene. Experts have taken all of this to mean intron insertions are extremely rare events.

Almost all of the introns the IU Bloomington biologists located possessed a sequence of indeterminate origin. Only one of the 24 identified sequences bore a resemblance to a specific DNA sequences associated either with the Daphnia genome or its parasites. The other 23 introns had sequences that appear to have been improvised by the machinery responsible for DNA synthesis. "Our molecular analyses have enabled us to reject a number of hypotheses for the mechanism of intron origins, while clearly indicating an entirely unexpected pathway -- emergence as accidents arising during the repair of double-strand breaks," Lynch said.

Abraham Tucker, now at Indiana University Bloomington, and paper co-author Way Sung were both graduate students of William Kelley Thomas at the University of New Hampshire's Hubbard Center for Genome Studies when they did the bioinformatic analysis of the Daphnia genome that led to the findings of this paper. Drawing on longtime collaborations between Lynch's lab and the Hubbard Center on the Daphniagenome project, the two were able to access all Daphniagenome sequences.

"It was a very intense analysis, but it was obvious within a few days that there was some very interesting data," says Thomas, who is Hubbard Professor in Genomics and director of the Hubbard Center for Genome Studies. "This was a wonderful collaborative project."

This research was funded with grants from the National Science Foundation.

Female Fruit Flies Can Be 'Too Attractive' to Males, Scientists Show

Females can be too attractive to the opposite sex -- too attractive for their own good -- say biologists at UC Santa Barbara. They found that, among fruit flies, too much male attention directed toward attractive females leads to smaller families and, ultimately, to a reduced rate of population-wide adaptive evolution.

In an article published in the December 8 issue of Public Library of Science Biology, the authors described their experiments on the sex lives of fruit flies.

"Can females be too good looking?" asks William Rice, biology professor at UCSB. "Can there be disadvantages to being attractive? The answer is yes: If you are too attractive, you get too much male attention, and that interferes with your ability to function biologically."

The authors explain that the term "good looking," among fruit flies, refers to something, like a large body. From the perspective of a male fly, a desirable mate is a female that is larger and can therefore produce more offspring.

"These larger females are disproportionately courted and harassed by males attempting to obtain matings," said Tristan A. F. Long, the study's first author. "When these males are 'choosy' with their courtship, there may be negative consequences to the species' ability to adaptively evolve."

According to the scientists, too much mating is harmful to the females because seminal fluid from the male has toxic side effects. Too much courtship can also hinder the female's ability to forage effectively.

"When they court the females, the males sing to them; they do this by vibrating their wings," said Rice. "They dance and sing at the same time. This might sound romantic, and it would be if it only happened once. But males are doing it all the time. This courtship is unrelenting -- like mosquitoes on a warm summer night -- as the male fruit flies try to persuade females to mate. The males are so persistent that they get them to mate almost every day."

In many species, females are frequently subject to intense courtship "harassment" from males attempting to obtain additional matings, according to the researchers. These coercive activities can result in attractive females becoming less fit to reproduce -- a factor that has a major effect on the entire population.

"We found that when harmful courtship behaviors were directed predominantly toward larger females of greater fecundity potential -- and away from smaller females, of lesser fecundity potential -- this resulted in an overall reduction in the variation of lifetime reproductive success of females in the population," said Long.

The male-mediated, persistent courtship bias can have important consequences for the ability of a population to adaptively change over time. If, for example, a female acquires a mutation that increases metabolic efficiency, allowing her to grow larger, and produce more offspring over her lifetime, this mutation should rapidly spread through the population. However, if the males get in the way of the biological success of these more attractive females, the mutation won't spread through the population as well as it might if males courted females indiscriminately.

The experiments clearly showed that the evolutionary adaptation of fruit flies is hindered by this mating situation. "This change in the distribution of fitness represents a previously unappreciated aspect of sexual selection -- one with important implications for the ability of beneficial genetic variation to spread through the gene pool, and ultimately for a species' capacity to adaptively evolve," Long explained.

Long was a Natural Sciences and Engineering Research Council of Canada (NSERC) postdoctoral fellow at UCSB at the time that he carried out the experiments designed with Rice. Long is currently a postdoctoral fellow with the University of Toronto in the Department of Ecology and Evolutionary Biology. The other authors are Alison Pischedda, a graduate student, and Andrew D. Stewart, a postdoctoral fellow, both of UCSB.

Gaining Advantages From Childhood Experience

It often seems that certain aspects of our personalities are influenced by events that occurred in our childhoods. A recent study by Dr. Akaysha Tang's research team from the University of New Mexico Psychology Department and collaborators at Rockefeller University examined how early life experience influences social skills and ability to handle stressful situations using a rat model. The study will be published on July 30th in the online, open-access journal PLoS ONE.

In this study, Dr. Tang and colleagues examined whether rats that experienced greater novelty by spending three minutes a day away from their familiar home environment during infancy had a greater ability to compete against other rats for exclusive access to chocolate reward compared to their siblings that stayed in the home environment during infancy. They found that novelty-exposed rats were able to "beat out" their competitors more often than their home-staying siblings. They also found that across repeated sessions of competition, novelty-exposed rats decreased their release of stress hormones into the bloodstream, suggesting that they adapted faster to the stressful situation.

These findings were made among rats that were 24 months of age—considered old age for a rat. Perhaps most remarkably, the differences in early experience were induced by approximately 60 minutes of cumulative differential treatment carried out during the first 3 weeks of life. This means that very brief exposures to a novel environment during infancy can have a life-long influence on social competitive ability and the stress response.

Another question asked by Dr. Tang and colleagues was whether the differences between siblings depended on the care received from their mothers during infancy. They measured how much mother rats licked and groomed their pups after the novelty exposure procedure and how consistently they provided this care from day to day. They discovered that the mother rats that delivered more care to their pups on average were inconsistent in their amount of care from day to day. This led to the surprising finding that the novelty-exposed rats with the most adaptive stress responses had mothers that gave highly consistent, but lesser amounts, of care.

In translating possible significance of these findings to the human species, although it is sometimes assumed that the overall amount of care from the mother is one of the most important influences on her children's development, this study by Dr. Tang and colleagues provides a different view—that the consistency of maternal care may be more important than the amount of maternal care and that other sources of influences, such as environmental novelty can play an important role in shaping a child's development.

If You're Feeling Helpless, It May Be Best To Be Alone

If you're going to experience a period of helplessness, it's best to be alone. New research at the University of Haifa found that laboratory rats that were on their own when exposed to uncontrollable conditions, which create a feeling of helplessness, learned to avoid situations which create such feelings better than rats that were exposed to uncontrollable conditions in pairs.

The way laboratory rats react to uncontrollable situations in which their behaviors have no influence on subsequent events has been researched in the past. Results show that rats that are exposed to a situation in which they are powerless, for example, electric shocks that they can't possibly avoid, have a more difficult time learning how to avoid them in the future than rats that were never exposed to situations of helplessness -- a phenomenon known as "learned helplessness."

Researchers choose to experiment with rats because they are know as social animals and their brains work much the same way as human brains. However, most of the research done until now was done on rats exposed to uncontrollable conditions when they are alone.

In his doctoral dissertation, Dr. Qutaiba Agbaria, under the supervision of Dr. Richard Shuster, examined the differences in learned helplessness among rats that were exposed to uncontrollable conditions alone and in pairs. The researcher began with the hypothesis that rats would learn to be more adaptable in social situations, or in pairs, however, the research results revealed a very different picture. Rats that were exposed to uncontrollable conditions in pairs coped less well when they were no longer in uncontrollable situations than rats that were exposed to these situations alone.

The next phase of the research examined the influence of a rat that had never been exposed to an uncontrollable situation on a rat that had. These pairs of rats showed greater adaptability than pairs that had been exposed to helplessness as individuals or in pairs. In addition, the researchers did not find outstanding differences between the learning ability of these pairs of rats -- where one had been exposed to uncontrollable conditions and the other hadn't -- and pairs that were never exposed to uncontrollable conditions, which means that the effect of "learned helplessness" is effectively erased. "Now that we have see that "learned helplessness" can be "unlearned", we should continue to examine whether this change is a result of exposure to a rat that was not exposed to helplessness or rather that the social behavior between the two animals has another meaning," said Dr. Agbaria.

Social Scientists Build Case for 'Survival of the Kindest'

Researchers at the University of California, Berkeley, are challenging long-held beliefs that human beings are wired to be selfish. In a wide range of studies, social scientists are amassing a growing body of evidence to show we are evolving to become more compassionate and collaborative in our quest to survive and thrive.

In contrast to "every man for himself" interpretations of Charles Darwin's theory of evolution by natural selection, Dacher Keltner, a UC Berkeley psychologist and author of "Born to be Good: The Science of a Meaningful Life," and his fellow social scientists are building the case that humans are successful as a species precisely because of our nurturing, altruistic and compassionate traits.

They call it "survival of the kindest."

"Because of our very vulnerable offspring, the fundamental task for human survival and gene replication is to take care of others," said Keltner, co-director of UC Berkeley's Greater Good Science Center. "Human beings have survived as a species because we have evolved the capacities to care for those in need and to cooperate. As Darwin long ago surmised, sympathy is our strongest instinct."

Empathy in our genes

Keltner's team is looking into how the human capacity to care and cooperate is wired into particular regions of the brain and nervous system. One recent study found compelling evidence that many of us are genetically predisposed to be empathetic.

The study, led by UC Berkeley graduate student Laura Saslow and Sarina Rodrigues of Oregon State University, found that people with a particular variation of the oxytocin gene receptor are more adept at reading the emotional state of others, and get less stressed out under tense circumstances.

Informally known as the "cuddle hormone," oxytocin is secreted into the bloodstream and the brain, where it promotes social interaction, nurturing and romantic love, among other functions.

"The tendency to be more empathetic may be influenced by a single gene," Rodrigues said.

The more you give, the more respect you get

While studies show that bonding and making social connections can make for a healthier, more meaningful life, the larger question some UC Berkeley researchers are asking is, "How do these traits ensure our survival and raise our status among our peers?"

One answer, according to UC Berkeley social psychologist and sociologist Robb Willer is that the more generous we are, the more respect and influence we wield. In one recent study, Willer and his team gave participants each a modest amount of cash and directed them to play games of varying complexity that would benefit the "public good." The results, published in the journal American Sociological Review, showed that participants who acted more generously received more gifts, respect and cooperation from their peers and wielded more influence over them.

"The findings suggest that anyone who acts only in his or her narrow self-interest will be shunned, disrespected, even hated," Willer said. "But those who behave generously with others are held in high esteem by their peers and thus rise in status."

"Given how much is to be gained through generosity, social scientists increasingly wonder less why people are ever generous and more why they are ever selfish," he added.

Cultivating the greater good

Such results validate the findings of such "positive psychology" pioneers as Martin Seligman, a professor at the University of Pennsylvania whose research in the early 1990s shifted away from mental illness and dysfunction, delving instead into the mysteries of human resilience and optimism.

While much of the positive psychology being studied around the nation is focused on personal fulfillment and happiness, UC Berkeley researchers have narrowed their investigation into how it contributes to the greater societal good.

One outcome is the campus's Greater Good Science Center, a West Coast magnet for research on gratitude, compassion, altruism, awe and positive parenting, whose benefactors include the Metanexus Institute, Tom and Ruth Ann Hornaday and the Quality of Life Foundation.

Christine Carter, executive director of the Greater Good Science Center, is creator of the "Science for Raising Happy Kids" Web site, whose goal, among other things, is to assist in and promote the rearing of "emotionally literate" children. Carter translates rigorous research into practical parenting advice. She says many parents are turning away from materialistic or competitive activities, and rethinking what will bring their families true happiness and well-being.

"I've found that parents who start consciously cultivating gratitude and generosity in their children quickly see how much happier and more resilient their children become," said Carter, author of "Raising Happiness: 10 Simple Steps for More Joyful Kids and Happier Parents" which will be in bookstores in February 2010. "What is often surprising to parents is how much happier they themselves also become."

The sympathetic touch

As for college-goers, UC Berkeley psychologist Rodolfo Mendoza-Denton has found that cross-racial and cross-ethnic friendships can improve the social and academic experience on campuses. In one set of findings, published in the Journal of Personality and Social Psychology, he found that the cortisol levels of both white and Latino students dropped as they got to know each over a series of one-on-one get-togethers. Cortisol is a hormone triggered by stress and anxiety.

Meanwhile, in their investigation of the neurobiological roots of positive emotions, Keltner and his team are zeroing in on the aforementioned oxytocin as well as the vagus nerve, a uniquely mammalian system that connects to all the body's organs and regulates heart rate and breathing.

Both the vagus nerve and oxytocin play a role in communicating and calming. In one UC Berkeley study, for example, two people separated by a barrier took turns trying to communicate emotions to one another by touching one other through a hole in the barrier. For the most part, participants were able to successfully communicate sympathy, love and gratitude and even assuage major anxiety.

Researchers were able to see from activity in the threat response region of the brain that many of the female participants grew anxious as they waited to be touched. However, as soon as they felt a sympathetic touch, the vagus nerve was activated and oxytocin was released, calming them immediately.

"Sympathy is indeed wired into our brains and bodies; and it spreads from one person to another through touch," Keltner said.

The same goes for smaller mammals. UC Berkeley psychologist Darlene Francis and Michael Meaney, a professor of biological psychiatry and neurology at McGill University, found that rat pups whose mothers licked, groomed and generally nurtured them showed reduced levels of stress hormones, including cortisol, and had generally more robust immune systems.

Overall, these and other findings at UC Berkeley challenge the assumption that nice guys finish last, and instead support the hypothesis that humans, if adequately nurtured and supported, tend to err on the side of compassion.

"This new science of altruism and the physiological underpinnings of compassion is finally catching up with Darwin's observations nearly 130 years ago, that sympathy is our strongest instinct," Keltner said.

Are Angry Women More Like Men?

"Why is it that men can be bastards and women must wear pearls and smile?" wrote author Lynn Hecht Schafran. The answer, according to an article in the Journal of Vision, may lie in our interpretation of facial expressions.

In two studies, researchers asked subjects to identify the sex of a series of faces. In the first study, androgynous faces with lowered eyebrows and tight lips (angry expressions) were more likely to be identified as male, and faces with smiles and raised eyebrows (expressions of happiness and fear) were often labeled feminine.

The second study used male and female faces wearing expressions of happiness, anger, sadness, fear or a neutral expression. Overall, subjects were able to identify male faces more quickly than female faces, and female faces that expressed anger took the longest to identify.

"The present research shows that the association between anger and men and happiness and women is so strong that it can influence the decisions about the gender of another person when that person is viewed briefly," said Ursula Hess, PhD, from the Department of Psychology, University of Quebec at Montreal.

According to the report, the findings from this study as well as others lead to the idea that "the face is a complex social signaling system in which signals for emotion, behavioral intentions and sex all overlap."

Hess said that the same cues that make a face appear male -- a high forehead, a square jaw and thicker eyebrows -- have been linked to perceptions of dominance. Likewise, features that make a face appear female -- a rounded, baby face with large eyes -- have been linked to perceptions of the individual being approachable and warm.

"This difference in how the emotions and social traits of the two sexes are perceived could have significant implications for social interactions in a number of settings. Our research demonstrates that equivalent levels of anger are perceived as more intense when shown by men rather than women, and happiness as more intense when shown by women rather than men. It also suggests that it is less likely for men to be perceived as warm and caring and for women to be perceived as dominant."

First Evidence of Brain Rewiring in Children: Reading Remediation Positively Alters Brain Tissue

Carnegie Mellon University scientists Timothy Keller and Marcel Just have uncovered the first evidence that intensive instruction to improve reading skills in young children causes the brain to physically rewire itself, creating new white matter that improves communication within the brain.

As the researchers report today in the journal Neuron, brain imaging of children between the ages of 8 and 10 showed that the quality of white matter -- the brain tissue that carries signals between areas of grey matter, where information is processed -- improved substantially after the children received 100 hours of remedial training. After the training, imaging indicated that the capability of the white matter to transmit signals efficiently had increased, and testing showed the children could read better.

"Showing that it's possible to rewire a brain's white matter has important implications for treating reading disabilities and other developmental disorders, including autism," said Just, the D.O. Hebb Professor of Psychology and director of Carnegie Mellon's Center for Cognitive Brain Imaging (CCBI).

Dr. Thomas R. Insel, director of the National Institute of Mental Health, agreed. "We have known that behavioral training can enhance brain function. The exciting breakthrough here is detecting changes in brain connectivity with behavioral treatment. This finding with reading deficits suggests an exciting new approach to be tested in the treatment of mental disorders, which increasingly appear to be due to problems in specific brain circuits," Insel said.

Keller and Just's study was designed to discover what physically changes in the brains of poor readers who make the transition to good reading. They scanned the brains of 72 children before and after they went through a six-month remedial instruction program. Using diffusion tensor imaging (DTI), a new brain imaging technique that tracks water movement in order to reveal the microscopic structure of white matter, Keller and Just found a brain change involving the white matter cabling that wires different parts of the brain together.

"Water molecules that are inside nerve fibers tend to move or diffuse parallel to the nerve fibers," explained Keller, a CCBI research scientist and author of the first developmental study of compromised white matter in autism. "To track the nerve fibers, the scanner senses areas in which many water molecules are moving along in the same direction and produces a road-map of the brain's wiring."

Previous DTI studies had shown that both children and adults with reading difficulty displayed areas of compromised white matter. This new study shows that 100 hours of intensive reading instruction improved children's reading skills and also increased the quality of the compromised white matter to normal levels. More precisely, the DTI imaging illustrated that the consistency of water diffusion had increased in this region, indicating an improvement in the integrity of the white matter tracts.

"The improved integrity essentially increases communication bandwidth between the two brain areas that the white matter connects, by a factor of 10," Just said. "This opens a new era of being able to see the brain wiring change when an effective instructional treatment is applied. It lets us see educational interventions from a new perspective."

Out of the 72 children, 47 were poor readers and 25 were reading at a normal level. The good readers and a group of 12 poor readers did not receive the remedial instruction, and their brain scans did not show any changes. "The lack of change in the control groups demonstrates that the change in the treated group cannot be attributed to naturally occurring maturation during the study," Keller said.

Keller and Just also found that the amount of change in diffusion among the treated group was directly related to the amount of increase in phonological decoding ability. The children who showed the most white matter change also showed the most improvement in reading ability, confirming the link between the brain tissue alteration and reading progress.

Additional analyses indicated that the change resulted from a decrease in the movement of water perpendicular to the main axes of the underlying white matter fibers, a finding consistent with increased myelin content in the region. Although the authors caution that further research will be necessary to uncover the precise mechanism for the change in white matter, some previous findings indicate a role for electrical activity along axons in promoting the formation of myelin around them, providing a plausible physiological basis for intensive practice and instruction increasing the efficiency of communication among brain areas.

"We're excited about these results," Just said. "The indication that behavioral intervention can improve both cognitive performance and the microstructure of white matter tracts is a breakthrough for treating and understanding development problems."