SETTLING FOR ‘MR. RIGHT NOW’ BETTER THAN WAITING FOR ‘MR. RIGHT’

Evolutionary researchers have determined that settling for “Mr. Okay” is a better evolutionary strategy than waiting for “Mr. Perfect.” When studying the evolution of risk aversion researchers found that it is in our nature – traced back to the earliest humans – to take the safe bet when stakes are high, such as whether or not we will mate. Photo by D.L. Turner

Evolutionary researchers have determined that settling for “Mr. Okay” is a better evolutionary strategy than waiting for “Mr. Perfect.”

When studying the evolution of risk aversion, Michigan State University researchers found that it is in our nature – traced back to the earliest humans – to take the safe bet when stakes are high, such as whether or not we will mate.

“Primitive humans were likely forced to bet on whether or not they could find a better mate,” said Chris Adami, MSU professor of microbiology and molecular genetics and co-author of the paper.

“They could either choose to mate with the first, potentially inferior, companion and risk inferior offspring, or they could wait for Mr. or Ms. Perfect to come around,” he said. “If they chose to wait, they risk never mating.”

Adami and his co-author Arend Hintze, MSU research associate, used a computational model to trace risk-taking behaviors through thousands of generations of evolution with digital organisms. These organisms were programmed to make bets in high-payoff gambles, which reflect the life-altering decisions that natural organisms must make, as for example choosing a mate.

“An individual might hold out to find the perfect mate but run the risk of coming up empty and leaving no progeny,” Adami said. “Settling early for the sure bet gives you an evolutionary advantage, if living in a small group.”

Adami and his team tested many variables that influence risk-taking behavior and concluded that certain conditions influence our decision-making process. The decision must be a rare, once-in-a-lifetime event and also have a high payoff for the individual’s future – such as the odds of producing offspring.

How risk averse we are correlates to the size of the group in which we were raised. If reared in a small group – fewer than 150 people – we tend to be much more risk averse than those who were part of a larger community.

It turns out that primitive humans lived in smaller groups, about 150 individuals. Because resources tend to be more scarce in smaller communities, this environment helps promote risk aversion.

“We found that it is really the group size, not the total population size, which matters in the evolution of risk aversion,” Hintze said.

However, not everyone develops the same level of aversion to risk. The study also found that evolution doesn’t prefer one single, optimal way of dealing with risk, but instead allows for a range of less, and sometimes more-risky, behaviors to evolve.

“We do not all evolve to be the same,” Adami said. “Evolution creates a diversity in our acceptance of risk, so you see some people who are more likely to take bigger risks than others. We see the same phenomenon in our simulations.”

The research was part of an interdisciplinary collaboration with Ralph Hertwig of the Max Planck Institute for Human Development in Berlin.

Also contributing to the study was Randal Olson, graduate student, MSU Department of Computer Science and Engineering and BEACON Center for the Study of Evolution in Action.

Source: Michigan State University

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EGFR-Mediated Beclin 1 Phosphorylation in Autophagy Suppression, Tumor Progression, and Tumor Chemoresistance

EGFR negatively regulates autophagy by binding to Beclin 1.
Active EGFR phosphorylates Beclin 1 and alters its interactome.
EGFR suppression of Beclin 1 may contribute to tumor progression in lung cancer.

Lung cancer responses to EGFR inhibitors may involve activation of Beclin 1. Image Credit: Cell Press

Summary
Cell surface growth factor receptors couple environmental cues to the regulation of cytoplasmic homeostatic processes, including autophagy, and aberrant activation of such receptors is a common feature of human malignancies. Here, we defined the molecular basis by which the epidermal growth factor receptor (EGFR) tyrosine kinase regulates autophagy. Active EGFR binds the autophagy protein Beclin 1, leading to its multisite tyrosine phosphorylation, enhanced binding to inhibitors, and decreased Beclin 1-associated VPS34 kinase activity. EGFR tyrosine kinase inhibitor (TKI) therapy disrupts Beclin 1 tyrosine phosphorylation and binding to its inhibitors and restores autophagy in non-small-cell lung carcinoma (NSCLC) cells with a TKI-sensitive EGFR mutation. In NSCLC tumor xenografts, the expression of a tyrosine phosphomimetic Beclin 1 mutant leads to reduced autophagy, enhanced tumor growth, tumor dedifferentiation, and resistance to TKI therapy. Thus, oncogenic receptor tyrosine kinases directly regulate the core autophagy machinery, which may contribute to tumor progression and chemoresistance.

Introduction
Epidermal growth factor receptor (EGFR), an oncogenic receptor tyrosine kinase, links extracellular signals to cellular homeostasis. In normal cells, EGFR signaling is triggered by the binding of growth factors, such as epidermal growth factor (EGF), leading to homodimerization or heterodimerization with other EGFR family members (such as HER2/neu) and autophosphorylation of the intracellular domain (Lemmon and Schlessinger, 2010). The phosphotyrosines formed serve as a docking site for adaptor molecules, which results in the activation of signaling pathways including the Ras/MAPK pathway, the PI3K/Akt pathway, and STAT signaling pathways. In tumor cells, the tyrosine kinase activity of EGFR may be dysregulated by EGFR gene mutation, increased EGFR gene copy number, or EGFR protein overexpression, leading to aberrant EGFR signaling and increased tumor cell survival, proliferation, invasion, and metastasis ( Ciardiello and Tortora, 2008). EGFR signaling is deregulated in many human cancers, including those of the lung, head and neck, colon, pancreas, and brain.

The deregulation of EGFR in human cancers has led to the development of anticancer agents that target EGFR, including: (1) anti-EGFR antibodies that inhibit ligand binding and (2) small-molecule receptor tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, that block EGFR intracellular tyrosine kinase activity. Although the EGFR TKIs have shown limited clinical benefit in the majority of solid tumors, they are effective in non-small-cell lung carcinomas (NSCLCs) that harbor specific mutations in the tyrosine kinase domain of EGFR (most commonly, in-frame deletion in exon 19 around codons 746–750 or single-base substitution, L858R, in exon 21) (Ciardiello and Tortora, 2008, Lynch et al., 2004 and Pao and Chmielecki, 2010). Most patients with NSCLCs with EGFR mutations initially respond favorably to erlotinib or gefitinib, suggesting these mutations drive tumorigenesis. However, among tumors that initially respond to EGFR TKIs, most eventually acquire resistance, often due to the emergence of a secondary mutation, T790M, in the kinase domain of EGFR (Pao and Chmielecki, 2010).

Several studies have shown that EGFR signaling regulates autophagy, a lysosomal degradation pathway that functions in cellular homeostasis and protection against a variety of diseases, including cancer (Levine and Kroemer, 2008). The downstream targets of EGFR—PI3K, Akt, and mammalian target of rapamycin (mTOR)—are well-established negative regulators of autophagy (Botti et al., 2006). Moreover, EGFR inhibitors induce autophagy in NSCLCs (Gorzalczany et al., 2011 and Han et al., 2011) and other cancer cells (Fung et al., 2012). However, the links between EGFR signaling and autophagy remain poorly understood, particularly (1) the molecular mechanisms by which EGFR signaling suppresses autophagy, (2) the role of EGFR suppression of autophagy in lung cancer pathogenesis, and (3) the role of autophagy induction in the response to TKI therapy. EGFR inhibitor-induced autophagy in lung cancer cells has been postulated to exert either cytoprotective (Han et al., 2011) or cytotoxic (Gorzalczany et al., 2011) effects.

Conflicting results regarding the role of autophagy in the response or resistance to EGFR TKI treatment reflects broader uncertainties in the role of autophagy in cancer therapy (Rubinsztein et al., 2012). It is not understood in what contexts autophagy induction contributes to tumor progression or suppression and to tumor chemoresistance or chemosensitivity. There is a general consensus that autophagy prevents tumor initiation, as loss-of-function mutations of several different autophagy genes results in spontaneous tumorigenesis (beclin 1, Atg5, and Atg7) and/or increased chemical-induced tumorigenesis (Atg4C) in mice ( Rubinsztein et al., 2012). Despite this inhibitory role in tumor initiation, it has been proposed that autophagy may promote the growth of established tumors and contribute to chemoresistance, principally through its actions to prolong the survival of metabolically stressed neoplastic cells ( Rubinsztein et al., 2012).

To understand the relationship between oncogenic signaling, autophagy, and distinct stages of tumorigenesis, it is important to define the molecular mechanisms by which oncogenic signaling regulates autophagy. We recently showed that the oncogene Akt inhibits autophagy independently of mTOR signaling via serine phosphorylation of the essential autophagy protein, Beclin 1 (Wang et al., 2012), a haploinsufficient tumor suppressor protein frequently monoallelically deleted in human breast and ovarian cancer (Levine and Kroemer, 2008). Moreover, Akt-mediated phosphorylation of Beclin 1 contributes to Akt-dependent fibroblast transformation, supporting the concept that inactivation of Beclin 1-dependent autophagy plays a role in tumor initiation. However, it is not known whether oncogenic inactivation of Beclin 1 (or other autophagy proteins) influences progression of established tumors and/or their response to therapy.


Here, we identify the molecular basis by which EGFR tyrosine kinase activity regulates autophagy. We show that active EGFR binds to Beclin 1, leading to its tyrosine phosphorylation, alteration of its interactome, and inhibition of its autophagy function. A mutant of Beclin 1 containing phosphomimetic mutations in the EGFR-dependent tyrosine phosphorylation sites enhances autophagy suppression in EGFR-mutated NSCLC cells, resulting in enhanced tumor progression, altered tumor cell differentiation, and partial tumor resistance to EGFR TKI therapy. These findings demonstrate a heretofore unknown link between oncogenic receptor tyrosine kinases and the autophagy machinery, which may contribute to tumor progression and resistance to targeted therapy.

Source: Full Artical At - CELL PRESS

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Why do zebras have stripes?

A mother zebra with a foal in Tanzania’s Tarangire National Park. Credit: Brenda Larison/UCLA

One of nature’s fascinating questions is how zebras got their stripes.

A team of life scientists led by UCLA’s Brenda Larison has found at least part of the answer: The amount and intensity of striping can be best predicted by the temperature of the environment in which zebras live.

In the January cover story of the Royal Society’s online journal, Open Science, the researchers make the case that the association between striping and temperature likely points to multiple benefits — including controlling zebras’ body temperature and protecting them from diseases carried by biting flies.

“While past studies have typically focused their search for single mechanisms, we illustrate in this study how the cause of this extraordinary phenomenon is actually likely much more complex than previously appreciated, with temperature playing an important role,” said Thomas B. Smith, professor of ecology and evolutionary biology in the UCLA College and senior author of the research.

Larison, a researcher in UCLA’s department of ecology and evolutionary biology and the study’s lead author, and her colleagues examined the plains zebra, which is the most common of three zebra species and has a wide variety of stripe patterns. On zebras in warmer climes, the stripes are bold and cover the entire body. On others — particularly those in regions with colder winters such as South Africa and Namibia — the stripes are fewer in number and are lighter and narrower. In some cases, the legs or other body parts have virtually no striping.

Zebras evolved from horses more than 2 million years ago, biologists have found. Scientists have previously hypothesized that zebras’ stripes evolved for one, or a combination of, four main reasons: confusing predators, protecting against disease-carrying insects, controlling body temperature and social cohesion. And while numerous previous studies of the phenomenon focused on a single hypothesis, the Larison-led study was the first to fully test a large set of hypotheses against one another.

Analyzing zebras at 16 locations in Africa and considering more two dozen environmental factors, the researchers found that temperature was the strongest predictor of zebras’ striping. The finding provides the first evidence that controlling body temperature, or thermoregulation, is the main reason for the stripes and the patterns they form.
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Separate research by Daniel Rubenstein, a Princeton University professor of ecology and evolutionary biology and a co-author of the Open Science paper, and Princeton undergraduate Damaris Iriondo strongly suggests that boldly striped zebras have external body temperatures about five degrees Fahrenheit cooler than other animals of the same size — like antelopes — that do not have stripes but live in the same areas. The Rubenstein study is not yet published, but it is cited in the Open Science paper.

Larison has studied many zebras during her field work throughout Africa — including in Kenya, South Africa, Tanzania, Uganda and Zimbabwe. Using the fact that their stripes are unique like fingerprints, she is able to distinguish one zebra from another.

In addition to Rubenstein, arguably the world’s leading expert on zebras, the study’s co-authors were Alec Chan-Golston and Elizabeth Li, former UCLA undergraduates in mathematics; Ryan Harrigan, an assistant adjunct professor in UCLA’s Center for Tropical Research; and Henri Thomassen, a former UCLA postdoctoral scholar and current research associate at the Institute for Evolution and Ecology at Germany’s University of Tübingen.

The research was supported by the National Geographic Society Committee for Research and Exploration.

Larison and her research team have also collected zebra tissue samples and have used cutting-edge technology to sequence zebra DNA to try to identify which genes code for striping. The team is continuing to study the benefits stripes provide.

Source: UCLA

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Charged graphene gives DNA a stage to perform molecular gymnastics

DNA interacts with charged graphene and contorts into sequence-specific shapes when the charge is changed. Credit: Photo courtesy Alek Aksimentiev

When Illinois researchers set out to investigate a method to control how DNA moves through a tiny sequencing device, they did not know they were about to witness a display of molecular gymnastics.

Fast, accurate and affordable DNA sequencing is the first step toward personalized medicine. Threading a DNA molecule through a tiny hole, called a nanopore, in a sheet of graphene allows researchers to read the DNA sequence; however, they have limited control over how fast the DNA moves through the pore. In a new study published in the journal Nature Communications, University of Illinois physics professor Aleksei Aksimentiev and graduate student Manish Shankla applied an electric charge to the graphene sheet, hoping that the DNA would react to the charge in a way that would let them control its movement down to each individual link, or nucleotide, in the DNA chain.

"Ideally, you would want to step the DNA through the nanopore one nucleotide at a time," said Aksimentiev. "Take a measurement and then have another nucleotide in the sensing hole. That's the goal, and it hasn't been realized yet. We show that, to some degree, we can control the process by charging the graphene."

The researchers found that a positive charge in the graphene speeds up DNA movement through the nanopore, while a negative charge stops the DNA in its tracks. However, as they watched, the DNA seemed to dance across the graphene surface, pirouetting into shapes they had never seen, specific to the sequence of the DNA nucleotides.

"It reminds me of Swan Lake," Aksimentiev said. "It's very acrobatic. We were very surprised by the variety of DNA conformations that we can observe at the surface of graphene when we charge it. There is one sequence that starts out laying down on the surface, and when we change the charge, they all tilt on the side like they are doing a one-armed push-up. Then we also have nucleotides that would lay back, or go up like a ballerina en pointe."

Aksimentiev hypothesizes that the conformations are so different and so specific to the sequence because each nucleotide has a slightly different distribution of electrons, the negatively charged parts of the atoms. There is even a visible difference when a nucleotide is methylated, a tiny chemical change that can turn a gene on or off.

By switching the charge in the graphene, the researchers can control not only the DNA's motion through the pore, but also the shape the DNA contorts into.

"Because it's reversible, we can force it to adopt one conformation and then force it to go back. That's why we call it gymnastics," Aksimentiev said.

The researchers extensively used the Blue Waters supercomputer at the National Center for Supercomputing Applications, housed at the University of Illinois. They mapped each individual atom in the complex DNA molecule and ran numerous simulations of many different DNA sequences. Supercomputing power was essential to carrying out the work, Aksimentiev said.

"This is a really computationally intensive project," he said. "Having access to Blue Waters was essential because with the sheer number of simulations, we would not have been able to finish them. It would have taken too long."

The next step is to combine a charged nanopore setup with a sensor to build a DNA sequencing device that would incorporate both motion control and nucleotide recognition. The researchers also hope to explore the unexpected conformational changes for insights into epigenetics, the field that studies how genes are expressed and moderated.

"DNA is much more complicated than just a double helix. It's a complex molecule that has many properties, and we are still uncovering them," Aksimentiev said.

Video animation of DNA dancing as the graphene charge changes:


Source: University of Illinois at Urbana-Champaign

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Software models more detailed evolutionary networks from genetic data

Phylogenetic networks depict the movement of genetic sequences from one species to another as a means of showing where horizontal gene transfer may have taken place. Software by scientists at Rice University aims to reveal far more about species’ evolutionary histories than traditional tree models are able to. Credit: Luay Nakhleh/Rice University

The tree has been an effective model of evolution for 150 years, but a Rice University computer scientist believes it's far too simple to illustrate the breadth of current knowledge.

Rice researcher Luay Nakhleh and his group have developed PhyloNet, an open-source software package that accounts for horizontal as well as vertical inheritance of genetic material among genomes. His "maximum likelihood" method, detailed this month in the Proceedings of the National Academy of Sciences, allows PhyloNet to infer network models that better describe the evolution of certain groups of species than do tree models.

"Inferring" in this case means analyzing genes to determine their evolutionary history with the highest probability -- the maximum likelihood -- of connections between species. Nakhleh and Rice colleague Christopher Jermaine recently won a $1.1 million National Science Foundation grant to analyze evolutionary patterns using Bayesian inference, a statistics-based technique to estimate probabilities based on a data set.

To build networks that account for all of the genetic connections between species, the software infers the probability of variations that phylogenetic trees can't illustrate, such as horizontal gene transfers. These transfers circumvent simple parent-to-offspring evolution and allow genetic variations to move from one species to another by means other than reproduction.

Biologists want to know when and how these transfers happened, but tree structures conceal such information. "When horizontal transfer occurs, as with the hybridization of two species, the tree model becomes inadequate to describe the evolutionary history, and networks that incorporate horizontal gene transfer become the more appropriate model," Nakhleh said.

Nakhleh's Java-based software accounts for incomplete lineage sorting, in which clues to gene evolution that don't match the established lineage of species appear in the genetic record.

"We are the first group to develop a general model that will allow biologists to estimate hybridization while accounting for all these complexities in evolution," Nakhleh said.

Most existing programs for phylogenetics (the study of evolutionary relationships) ignore such complexities. "They end up overestimating the amount of hybridization," Nakhleh said. 

"They start seeing lots of complexities in the data and say, 'Oh, it's complex here; it must be hybridization,' and end up inferring too much. Our method acknowledges that part of the complexity has nothing to do with hybridization; it has to do with other random processes that happened during evolution."

The Rice researchers used two data sets to test the new program. One, a computer-generated set of data that mimics a realistic model of evolution, allowed them to evaluate the accuracy of the program. The second involved multiple genomes of mice found across Europe and Asia. "There have been stories about mice hybridizing," Nakhleh said. "Now that we have the first method to allow for systematic analysis, we ran it on a very large amount of data from five mouse samples and we detected hybridization" -- most notably in the presence of a genetic signal from a mouse in Kazakhstan that found its way to mice in France and Germany, he said.

Nakhleh hopes evolutionary biologists will use PhyloNet to take a fresh look at the massive amount of genomic data collected over the past few decades. "The exciting thing for me about this is that biologists can now systematically go through lots of data they have generated and check to see if there has been hybridization."

Source: Rice University

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Statistical model predicts performance of hybrid rice

Long-grain rice

Genomic prediction, a new field of quantitative genetics, is a statistical approach to predicting the value of an economically important trait in a plant, such as yield or disease resistance. The method works if the trait is heritable, as many traits tend to be, and can be performed early in the life cycle of the plant, helping reduce costs.

Now a research team led by plant geneticists at the University of California, Riverside and Huazhong Agricultural University, China, has used the method to predict the performance of hybrid rice (for example, the yield, growth-rate and disease resistance). The new technology could potentially revolutionize hybrid breeding in agriculture.

The study, published online in the Proceedings of the National Academy of Sciences, is a pilot research project on rice. The technology can be easily extended, however, to other crops such as maize.

"Rice and maize are two main crops that depend on hybrid breeding," said Shizhong Xu, a professor of genetics in the UC Riverside Department of Botany and Plant Sciences, who co-led the research project. "If we can identify many high-performance hybrids in these crops and use these hybrids, we can substantially increase grain production to achieve global food security."

Genomic prediction uses genome-wide markers to predict future individuals or species. These markers are genes or DNA sequences with known locations on a chromosome. Genomic prediction differs from traditional predictions in that it skips the marker-detection step. The method simply uses all markers of the entire genome to predict a trait.

"Classical marker-assisted selection only uses markers that have large effects on the trait," Xu explained. "It ignores all markers with small effects. But many economically important traits are controlled by a large number of genes with small effects. Because the genomic prediction model captures all these small-effect genes, predictability is vastly improved."

Without genomic prediction, breeders must grow all possible crosses in the field to select the best cross (hybrid). For example, for 1000 inbred parents, the total number of crosses would be 499500.

"It is impossible to grow these many crosses in the field," Xu said. "However, with the genomic prediction technology, we can grow only, say, 500 crosses, then predict all the 499500 potential crosses, and select the best crosses based on the predicted values of these hybrids."

Xu noted that genomic prediction is particularly useful for predicting hybrids because hybrid DNA sequences are determined by their inbred parents.

"More cost-saving can be achieved because we do not need to measure the DNA sequences of the hybrids," he said. "Knowing the genotypes of the parents makes it possible to immediately know the genotype of the hybrid. Indeed, there is no need to measure the genotype of the hybrid. It is fully predicted by the model."

When the researchers incorporated "dominance" and "epistasis" into their prediction model, they found that predictability was improved. In genetics, dominance describes the joint action of two different alleles (copies) of a gene. For example, if one copy of a gene has a value of 1 and the other copy has a value of 2, the joint effect of the two alleles may be 4, indicating that the two alleles are not additive. In this case, dominance has occurred. Epistasis refers to any type of gene-gene interaction.

"By incorporating dominance and epistasis, we took into account all available information for prediction," Xu said. "It led to a more accurate prediction of a trait value."

Genomic prediction can be used to predict heritable human diseases. For example, many cancers are heritable and genome prediction can be performed to predict disease risk for a person.

Xu was joined in the research by Qifa Zhang and his student Dan Zhu at Huazhong Agricultural University, China.

Next the research team, led by Xu and Zhang, will design a field experiment to perform hybrid prediction in rice.

Source: University of California - Riverside

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Body weight heavily influenced by gut microbes: Genes shape body weight by affecting gut microbes

Body sizes (stock image). New research shows that our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body. Credit: © olly / Fotolia

Our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body, according to a study by researchers at King's College London and Cornell University.

By studying pairs of twins at King's Department of Twin Research, researchers identified a specific, little known bacterial family that is highly heritable and more common in individuals with low body weight. This microbe also protected against weight gain when transplanted into mice.

The results, published today in the journal Cell, could pave the way for personalised probiotic therapies that are optimised to reduce the risk of obesity-related diseases based on an individual's genetic make-up.

Previous research has linked both genetic variation and the composition of gut microbes to metabolic disease and obesity. Despite these shared effects, the relationship between human genetic variation and the diversity of gut microbes was presumed to be negligible.

In the study, funded by National Institutes of Health (NIH), researchers sequenced the genes of microbes found in more than 1,000 fecal samples from 416 pairs of twins. The abundances of specific types of microbes were found to be more similar in identical twins, who share 100 per cent of their genes, than in non-identical twins, who share on average only half of the genes that vary between people. These findings demonstrate that genes influence the composition of gut microbes.

The type of bacteria whose abundance was most heavily influenced by host genetics was a recently identified family called 'Christensenellaceae'. Members of this health-promoting bacterial family were more abundant in individuals with a low body weight than in obese individuals. Moreover, mice that were treated with this microbe gained less weight than untreated mice, suggesting that increasing the amounts of this microbe may help to prevent or reduce obesity.

Professor Tim Spector, Head of the Department of Twin Research and Genetic Epidemiology at King's College London, said: 'Our findings show that specific groups of microbes living in our gut could be protective against obesity -- and that their abundance is influenced by our genes. The human microbiome represents an exciting new target for dietary changes and treatments aimed at combating obesity.

'Twins have been incredibly valuable in uncovering these links -- but we now want to promote the use of microbiome testing more widely in the UK through the British Gut Project. This is a crowd-sourcing experiment that allows anyone with an interest in their diet and health to have their personal microbes tested genetically using a simple postal kit and a small donation via our website (www.britishgut.org). We want thousands to join up so we can continue to make major discoveries about the links between our gut and our health.'

Ruth Ley, Associate Professor at Cornell University in the United States, said: 'Up until now, variation in the abundances of gut microbes has been explained by diet, the environment, lifestyle, and health. This is the first study to firmly establish that certain types of gut microbes are heritable -- that their variation across a population is in part due to host genotype variation, not just environmental influences. These results will also help us find new predictors of disease and aid prevention.'

Source: King's College London

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Human faces are so variable because we evolved to look unique

The amazing variety of human faces -- far greater than that of most other animals -- is the result of evolutionary pressure to make each of us unique and easily recognizable. Credit: UC Berkeley

The amazing variety of human faces -- far greater than that of most other animals -- is the result of evolutionary pressure to make each of us unique and easily recognizable, according to a new study by University of California, Berkeley, scientists.

Our highly visual social interactions are almost certainly the driver of this evolutionary trend, said behavioral ecologist Michael J. Sheehan, a postdoctoral fellow in UC Berkeley's Museum of Vertebrate Zoology. Many animals use smell or vocalization to identify individuals, making distinctive facial features unimportant, especially for animals that roam after dark, he said. But humans are different.

"Humans are phenomenally good at recognizing faces; there is a part of the brain specialized for that," Sheehan said. "Our study now shows that humans have been selected to be unique and easily recognizable. It is clearly beneficial for me to recognize others, but also beneficial for me to be recognizable. Otherwise, we would all look more similar."

"The idea that social interaction may have facilitated or led to selection for us to be individually recognizable implies that human social structure has driven the evolution of how we look," said coauthor Michael Nachman, a population geneticist, professor of integrative biology and director of the UC Berkeley Museum of Vertebrate Zoology.

The study will appear Sept. 16 in the online journal Nature Communications.

In the study, Sheehan said, "we asked, 'Are traits such as distance between the eyes or width of the nose variable just by chance, or has there been evolutionary selection to be more variable than they would be otherwise; more distinctive and more unique?'"

As predicted, the researchers found that facial traits are much more variable than other bodily traits, such as the length of the hand, and that facial traits are independent of other facial traits, unlike most body measures. People with longer arms, for example, typically have longer legs, while people with wider noses or widely spaced eyes don't have longer noses. Both findings suggest that facial variation has been enhanced through evolution.

Finally, they compared the genomes of people from around the world and found 

more genetic variation in the genomic regions that control facial characteristics than in other areas of the genome, a sign that variation is evolutionarily advantageous.

"All three predictions were met: facial traits are more variable and less correlated than other traits, and the genes that underlie them show higher levels of variation," Nachman said. "Lots of regions of the genome contribute to facial features, so you would expect the genetic variation to be subtle, and it is. But it is consistent and statistically significant."

Using Army data

Sheehan was able to assess human facial variability thanks to a U.S. Army database of body measurements compiled from male and female personnel in 1988. The Army Anthropometric Survey (ANSUR) data are used to design and size everything from uniforms and protective clothing to vehicles and workstations.

A statistical comparison of facial traits of European Americans and African Americans -- forehead-chin distance, ear height, nose width and distance between pupils, for example -- with other body traits -- forearm length, height at waist, etc. -- showed that facial traits are, on average, more varied than the others. The most variable traits are situated within the triangle of the eyes, mouth and nose.

Sheehan and Nachman also had access to data collected by the 1000 Genome project, which has sequenced more than 1,000 human genomes since 2008 and catalogued nearly 40 million genetic variations among humans worldwide. Looking at regions of the human genome that have been identified as determining the shape of the face, they found a much higher number of variants than for traits, such as height, not involving the face.

Prehistoric origins

"Genetic variation tends to be weeded out by natural selection in the case of traits that are essential to survival," Nachman said. "Here it is the opposite; selection is maintaining variation. All of this is consistent with the idea that there has been selection for variation to facilitate recognition of individuals."

They also compared the human genomes with recently sequenced genomes of Neanderthals and Denisovans and found similar genetic variation, which indicates that the facial variation in modern humans must have originated prior to the split between these different lineages.

"Clearly, we recognize people by many traits -- for example their height or their gait -- but our findings argue that the face is the predominant way we recognize people," Sheehan said.

Source: University of California - Berkeley

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Horses communicate with eyes and mobile ears

Author Jennifer Wathan is shown with study participant Bartie. Credit: Jennifer Wathan

Horses are sensitive to the facial expressions and attention of other horses, including the direction of the eyes and ears. The findings, reported in the Cell Press journal Current Biology on August 4, are a reminder for us humans to look beyond our own limitations and recognize that other species may communicate in ways that we can't, the researchers say. After all, human ears aren't mobile.

"Our study is the first to examine a potential cue to attention that humans do not have: the ears," says Jennifer Wathan of the University of Sussex. "Previous work investigating communication of attention in animals has focused on cues that humans use: body orientation, head orientation, and eye gaze; no one else had gone beyond that. However, we found that in horses their ear position was also a crucial visual signal that other horses respond to. In fact, horses need to see the detailed facial features of both eyes and ears before they use another horse's head direction to guide them."

The new study also challenges the earlier held notion that animals with eyes to the sides of their heads cannot glean information based on the direction of one another's gaze.

Wathan and the study's senior author Karen McComb took photographs to document cues given by horses when they were paying attention to something. Then Wathan and McComb used those photographs as life-sized models for other horses to look at as they chose between two feeding buckets. In each case, the horse in the photo was paying attention to one of the buckets and not the other. In some instances, the researchers also manipulated the image to remove information from key facial areas, including the eyes and the ears.

The researchers' observations show that horses rely on the head orientation of their peers to locate food. However, that ability to read each other's interest level is disrupted when parts of the face -- the eyes and ears -- are covered up with masks. The ability to correctly judge attention also varied depending on the identity of the horse pictured, suggesting that individual facial features may be important, the researchers report.

Wathan and McComb plan to continue to explore facial features related to the expression of emotion in their horses, noting that horses' rich social lives and close relationship to humans make them particularly interesting as study subjects. Our understanding of horses' social lives might also have implications for their welfare.

"Horses display some of the same complex and fluid social organization that we have as humans and that we also see in chimpanzees, elephants, and dolphins," Wathan says. "The challenges that living in these societies create, such as maintaining valuable social relationships on the basis of unpredictable interactions, are thought to have promoted the evolution of advanced social and communicative skills. There is a general interest in studying species with this social structure."

Source: Cell Press

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Birth of four foals from genotyped, cryopreserved embryos: A first in Europe

Genotyping allows scientists to choose the embryos they want to use based on different criteria: sex, like in this experiment, the absence of known genetic disorders, or, perhaps in the future, other traits that are tied to behavior, such as emotivity or sociability. Credit: INRA/C. Maitre

IFCE and INRA announced that, for the first time ever in Europe, four foals were successfully born as the result of the transfer of genotyped and cryopreserved embryos. The goal of this work is to better understand embryonic development, control livestock reproduction, and maintain breed genetic diversity. Furthermore, it is advantageous for the horse industry to be able to determine the traits of a future foal.

The INRA Val de Loire center at Nouzilly is where the technology to maintain embryo viability following genotyping and cryopreservation was honed, and then, last summer, the transfer of several embryos took place at the IFCE Haras du Pin Stud Farm, located in the French department of Orne. The partnership between the two institutions has now been cemented by the birth of the healthy foals.

What were the steps leading up to the birth of these foals?

Seven days after fertilization, embryos were collected from Welsh B ponies that are part of INRA's livestock. The embryos were genotyped: scientists sampled some of the embryos' cells to analyze their genomes. In this experiment, embryos were selected based on sex, the idea being to use sex-based selection to test the technique's feasibility. The embryos were then cryopreserved in liquid nitrogen (at -196°). Last summer, they were transferred into saddlebred mares at the Haras du Pin center. After an 11-month gestation period, the foals were born in May. They were of the expected sex: two females and two males. This is the first time that such an event has taken place in Europe, and it is the product of more than 10 years of various types of embryonic research carried out by INRA and IFCE scientists.

What made it so difficult to apply this technique to horses?

Although embryo preservation techniques are already well developed for bovines, small ruminant species, and even humans, preserving horse embryos is a very complex process. For instance, horse embryos vary greatly in size: 7-day-old embryos range in diameter from 200 to 700 micrometers. It is very difficult to cryopreserve the largest embryos because the liquid inside them forms ice crystals when the embryos are frozen at very cold temperatures. What's more, horse embryos are surrounded by a capsule that interferes with successful cryopreservation.

What is the significance of this event, which is the first of its kind in Europe?

There are several reasons why being able to successfully cryopreserve embryos is important. For example, it allows us to maintain breed genetic diversity, particularly that of breeds with small population sizes, such as the Landais or the Poitevin Mulassier. Furthermore, the factor that currently limits the use of embryo transfer is its cost: the transfer center has to maintain a team of recipient mares that are reproductively synchronized with the donor mares. Cryopreservation means that the transfer doesn't have to take place immediately; it can wait until a recipient mare becomes available to receive the embryo. Finally, it may now be possible to directly repopulate horse herds that have experienced losses as a result of various issues, such as disease-related problems, instead of having to use the indirect technique of crossbreeding.

Why genotype the embryos?

Genotyping allows us to choose the embryos we want to use based on different criteria: sex, like in this experiment, the absence of known genetic disorders, or, perhaps in the future, other traits that are tied to behavior, such as emotivity or sociability. It is advantageous for the horse industry to be able to determine the traits of a future foal. We will next aim to simplify the process -- to make this technology more accessible and user friendly for those in the horse industry.

Source: INRA-France

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Cat genome reveals clues to domestication​​

Cats and humans have shared the same households for at least 9,000 years, but we still know very little about how our feline friends became domesticated.

Cats and humans have shared the same households for at least 9,000 years, but we still know very little about how our feline friends became domesticated. An analysis of the cat genome led by researchers at Washington University School of Medicine in St. Louis reveals some surprising clues.

The research appears Nov. 10 in the Proceedings of the National Academy of Sciences Early Edition.

Cats have a relatively recent history of domestication compared with dogs; canines arose from wolves over 30,000 years ago.

"Cats, unlike dogs, are really only semidomesticated," said senior author Wes Warren, PhD, associate professor of genetics at The Genome Institute at Washington University​. "They only recently split off from wild cats, and some even still breed with their wild relatives. So we were surprised to find DNA evidence of their domestication."

One way scientists can understand the genetics of domestication is to look at what parts of the genome are altered in response to living together with humans, Warren added.
The researchers compared the genomes of domestic cats and wild cats, finding specific regions of the domestic cat genome that differed significantly.

The scientists found changes in the domestic cat's genes that other studies have shown are involved in behaviors such as memory, fear and reward-seeking. These types of behaviors -- particularly those when an animal seeks a reward -- generally are thought to be important in the domestication process.

"Humans most likely welcomed cats because they controlled rodents that consumed their grain harvests," said Warren. "We hypothesized that humans would offer cats food as a reward to stick around."

This meant that certain cats that would normally prefer to lead solitary lives in the wild had an additional incentive to stay with humans. Over time, humans preferred to keep cats that were more docile.

Cat genome project

The cat genome sequencing project, funded by the National Human Genome Research Institute, part of the National Institutes of Health (NIH), began in 2007. The project's initial goal was to study hereditary diseases in domestic cats, which are similar in some cases to those that afflict humans, including neurological disorders, and infectious and metabolic diseases.

To obtain the high-quality reference genome needed for this research, the team sequenced a domestic female Abyssinian cat named Cinnamon. They chose this particular cat because they could trace its lineage back several generations. This cat's family also had a particular degenerative eye disorder the researchers wanted to study.

To better understand characteristics of domestication, the researchers sequenced the genomes of select purebred domestic cats. Hallmarks of their domestication include features such as hair color, texture and patterns, as well as facial structure and how docile a cat is. Cats are bred for many of these types of characteristics. In fact, most modern breeds are the result of humans breeding cats for their favorite hair patterns.

The team also looked at a breed called Birman, which has characteristic white paws. The researchers traced the white pattern to just two small changes in a gene associated with hair color. They found that this genetic signature appears in all Birmans, likely showing that humans selectively bred these cats for their white paws and that the change to their genome happened in a remarkably short period of time.

The group also compared the cat genome with those of other mammals -- including a tiger, cow, dog and human -- to understand more about the genetics of cat biology.

"We looked at the underlying genetics to understand why certain abilities to survive in the wild evolved in cats and other carnivores," said Michael Montague, PhD, the study's first author and a postdoctoral research associate at The Genome Institute.

The differences they found in the cat genome help explain characteristics such as why cats are almost exclusively carnivorous and how their vision and sense of smell differ from other animals like dogs.

Solitary carnivores

To digest their fatty, meat-heavy meals, cats need genes to efficiently break down fats. The team found particular fat-metabolizing genes in carnivores such as cats and tigers that changed faster than can be explained by chance. This more rapid change generally means these genes provide some sort of digestive advantage to carnivores that only consume animal proteins. The researchers did not find such changes in the same genes of the cow and human, who eat more varied diets and would not need such enhancements.

Cats also rely less on smell to hunt than dogs. So it is not surprising that the researchers found fewer genes for smell in cats than dogs. But they did find more genes related to an alternate form of smell that detects chemicals called pheromones, which allow cats to monitor their social environment, including seeking out the opposite sex. This ability is not as important to dogs, which tend to travel in packs. But it is crucial in cats, which are more solitary and may have more difficulty finding mates.

Cats also have better hearing than most other carnivores, including an ability to hear in the ultrasonic range to better track prey. Their vision is also exceptional in low light.

"Cats tend to be more active at dawn and dusk," said Montague, "so they need to be able to detect movement in low light." Accordingly, the team identified specific genes that likely evolved to expand cats' hearing range and their vision in low light.

Even though the genomes of domestic cats have changed little since their split from wild cats, the new work shows that it is still possible to see evidence of the species' more recent domestication. "Using advanced genome sequencing technology, we were able to shed light on the genetic signatures of cats' unique biology and survival skills," said Warren. "And we were able to significantly jump start our knowledge about the evolution of cat domestication."

Collaborators in the research include Texas A&M University; University of Missouri-Columbia; University of California-Davis; Wellcome Trust Sanger Institute in the United Kingdom; Pompeu Fabra University in Spain; Centro de Analisis Genomico in Spain; Bilkent University in Turkey; Indiana Univeristy; Center for Cancer Research in Maryland; St. Petersburg State University in Russia; and Nova Southeastern University in Florida.

Source: Washington University in St. Louis

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A clear, molecular view of how human color vision evolved

Mountain Gorilla - Bwindi Uganda. “Gorillas and chimpanzees have human color vision,” Yokoyama says. “Or perhaps we should say that humans have gorilla and chimpanzee vision.” Credit: © Alexander / Fotolia

Many genetic mutations in visual pigments, spread over millions of years, were required for humans to evolve from a primitive mammal with a dim, shadowy view of the world into a greater ape able to see all the colors in a rainbow.

Now, after more than two decades of painstaking research, scientists have finished a detailed and complete picture of the evolution of human color vision. PLOS Genetics published the final pieces of this picture: The process for how humans switched from ultraviolet (UV) vision to violet vision, or the ability to see blue light.

"We have now traced all of the evolutionary pathways, going back 90 million years, that led to human color vision," says lead author Shozo Yokoyama, a biologist at Emory University. 

"We've clarified these molecular pathways at the chemical level, the genetic level and the functional level."

Co-authors of the PLOS Genetics paper include Emory biologists Jinyi Xing, Yang Liu and Davide Faggionato; Syracuse University biologist William Starmer; and Ahmet Altun, a chemist and former post-doc at Emory who is now at Fatih University in Istanbul, Turkey.

Yokoyama and various collaborators over the years have teased out secrets of the adaptive evolution of vision in humans and other vertebrates by studying ancestral molecules. The lengthy process involves first estimating and synthesizing ancestral proteins and pigments of a species, then conducting experiments on them. The technique combines microbiology with theoretical computation, biophysics, quantum chemistry and genetic engineering.

Five classes of opsin genes encode visual pigments for dim-light and color vision. Bits and pieces of the opsin genes change and vision adapts as the environment of a species changes.

Around 90 million years ago, our primitive mammalian ancestors were nocturnal and had UV-sensitive and red-sensitive color, giving them a bi-chromatic view of the world. By around 30 million years ago, our ancestors had evolved four classes of opsin genes, giving them the ability to see the full-color spectrum of visible light, except for UV.

"Gorillas and chimpanzees have human color vision," Yokoyama says. "Or perhaps we should say that humans have gorilla and chimpanzee vision."

For the PLOS Genetics paper, the researchers focused on the seven genetic mutations involved in losing UV vision and achieving the current function of a blue-sensitive pigment. 

They traced this progression from 90-to-30 million years ago.

The researchers identified 5,040 possible pathways for the amino acid changes required to bring about the genetic changes. "We did experiments for every one of these 5,040 possibilities," Yokoyama says. "We found that of the seven genetic changes required, each of them individually has no effect. It is only when several of the changes combine in a particular order that the evolutionary pathway can be completed."

In other words, just as an animal's external environment drives natural selection, so do changes in the animal's molecular environment.

In previous research, Yokoyama showed how the scabbardfish, which today spends much of its life at depths of 25 to 100 meters, needed just one genetic mutation to switch from UV to blue-light vision. Human ancestors, however, needed seven changes and these changes were spread over millions of years. "The evolution for our ancestors' vision was very slow, compared to this fish, probably because their environment changed much more slowly," 
Yokoyama says.

About 80 percent of the 5,040 pathways the researchers traced stopped in the middle, because a protein became non-functional. Chemist Ahmet Altun solved the mystery of why the protein got knocked out. It needs water to function, and if one mutation occurs before the other, it blocks the two water channels extending through the vision pigment's membrane.

"The remaining 20 percent of the pathways remained possible pathways, but our ancestors used only one," Yokoyama says. "We identified that path."

In 1990, Yokoyama identified the three specific amino acid changes that led to human ancestors developing a green-sensitive pigment. In 2008, he led an effort to construct the most extensive evolutionary tree for dim-light vision, including animals from eels to humans. At key branches of the tree, Yokoyama's lab engineered ancestral gene functions, in order to connect changes in the living environment to the molecular changes.

The PLOS Genetics paper completes the project for the evolution of human color vision. "We have no more ambiguities, down to the level of the expression of amino acids, for the mechanisms involved in this evolutionary pathway," Yokoyama says.

Source: Emory Health Sciences

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Hunter-gatherer past shows our fragile bones result from inactivity since invention of farming

Hunter-gatherer bone mass compared to agriculturalist bone mass. Credit: Timothy Ryan

New research across thousands of years of human evolution shows that our skeletons have become much lighter and more fragile since the invention of agriculture -- a result of our increasingly sedentary lifestyles as we shifted from foraging to farming.

The new study, published today in the journal PNAS, shows that, while human hunter-gatherers from around 7,000 years ago had bones comparable in strength to modern orangutans, farmers from the same area over 6,000 years later had significantly lighter and weaker bones that would have been more susceptible to breaking.

Bone mass was around 20% higher in the foragers -- the equivalent to what an average person would lose after three months of weightlessness in space.

After ruling out diet differences and changes in body size as possible causes, researchers have concluded that reductions in physical activity are the root cause of degradation in human bone strength across millennia. It is a trend that is reaching dangerous levels, they say, as people do less with their bodies today than ever before.

Researchers believe the findings support the idea that exercise rather than diet is the key to preventing heightened fracture risk and conditions such as osteoporosis in later life: more exercise in early life results in a higher peak of bone strength around the age of 30, meaning the inevitable weakening of bones with age is less detrimental.

There is, in fact, no anatomical reason why a person born today could not achieve the bone strength of an orangutan or early human forager, say researchers; but even the most physically active people alive are unlikely to be loading bones with enough frequent and intense stress to allow for the increased bone strength seen in the 'peak point' of traditional hunter-gatherers and non-human primate bones.

"Contemporary humans live in a cultural and technological milieu incompatible with our evolutionary adaptations. There's seven million years of hominid evolution geared towards action and physical activity for survival, but it's only in the last say 50 to 100 years that we've been so sedentary -- dangerously so," said co-author Dr Colin Shaw from the University of Cambridge's Phenotypic Adaptability, Variation and Evolution (PAVE) Research Group.

"Sitting in a car or in front of a desk is not what we have evolved to do."

The researchers x-rayed samples of human femur bones from the archaeological record, along with femora from other primate species, focusing on the inside of the femoral head: the ball at the top of the femur which fits into the pelvis to form the hip joint, one of the most load-bearing bone connections in the body.

Two types of tissue form bone: the cortical or 'hard' bone shell coating the outside, and the trabecular or 'spongy' bone: the honeycomb-like mesh encased within cortical shell that allows flexibility but is also vulnerable to fracture.

The researchers analysed the trabecular bone from the femoral head of four distinct archaeological human populations representing mobile hunter-gatherers and sedentary agriculturalists, all found in the same area of the US state of Illinois (and likely to be genetically similar as a consequence).

The trabecular structure is very similar in all populations, with one notable exception: within the mesh, hunter-gatherers have a much higher amount of actual bone relative to air.

"Trabecular bone has much greater plasticity than other bone, changing shape and direction depending on the loads imposed on it; it can change structure from being pin or rod-like to much thicker, almost plate-like. In the hunter-gatherer bones, everything was thickened," said Shaw.

This thickening is the result of constant loading on the bone from physical activity as hunter-gatherers roamed the landscape seeking sustenance. This fierce exertion would result in minor damage that caused the bone mesh to grow back ever stronger and thicker throughout life -- building to a 'peak point' of bone strength which counter-balanced the deterioration of bones with age.

Shaw believes there are valuable lessons to be learnt from the skeletons of our prehistoric predecessors. "You can absolutely morph even your bones so that they deal with stress and strain more effectively. Hip fractures, for example, don't have to happen simply because you get older if you build your bone strength up earlier in life, so that as you age it never drops below that level where fractures can easily occur."

Other theories for humans evolving a lighter, more fragile skeleton include changes in diet or selection for a more efficient, lighter skeleton, which was never reversed.

While the initial switch to farming did cause a dip in human health due to monoculture diets that lacked variety, the populations tested were unaffected by this window in history. "Of course we need a level of calcium to maintain bone heath, but beyond that level excess calcium isn't necessary," said Shaw.

The research also counters the theory that, at some point in human evolution, our bones just became lighter -- perhaps because there wasn't enough food to support a denser skeleton. "If that was true, human skeletons would be entirely distinct from other living primates. We've shown that hunter-gatherers fall right in line with primates of a similar body size. Modern human skeletons are not systemically fragile; we are not constrained by our anatomy."

"The fact is, we're human, we can be as strong as an orangutan -- we're just not, because we are not challenging our bones with enough loading, predisposing us to have weaker bones so that, as we age, situations arise where bones are breaking when, previously, they would not have" Shaw said.

While the 7,000-year-old foragers had vastly stronger bones than the 700-year-old farmers, Shaw says that neither competes with even earlier hominids from around 150,000 years ago. 

"Something is going on in the distant past to create bone strength that outguns anything in the last 10,000 years."

The next step for Shaw's research team will be to look at how different types of loading and mobility shape bodies and bones by cross-referencing archaeological records with testing on modern ultra-marathon runners, who cover punishing distances over a range of terrains -- from the Himalayas to the Namibian desert. He hopes this future work will provide insight into the kind of mobility that gave our ancient ancestors such powerful physical strength.

Source: University of Cambridge

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