Genes tell story of birdsong and human speech

The activity of genes related to singing shows a unique pattern in the brain of an Australian Budgerigar.
Credit: Duke University

His office is filled with all sorts of bird books, but Duke neuroscientist Erich Jarvis didn't become an expert on the avian family tree because of any particular interest in our feathered friends. Rather, it was his fascination with how the human brain understands and reproduces speech that brought him to the birds.

"We've known for many years that the singing behavior of birds is similar to speech in humans -- not identical, but similar -- and that the brain circuitry is similar, too," said Jarvis, an associate professor of neurobiology at the Duke University Medical School and an investigator at the Howard Hughes Medical Institute. "But we didn't know whether or not those features were the same because the genes were also the same."

Now scientists do know, and the answer is yes -- birds and humans use essentially the same genes to speak.

After a massive international effort to sequence and compare the entire genomes of 48 species of birds representing every major order of the bird family tree, Jarvis and his colleagues found that vocal learning evolved twice or maybe three times among songbirds, parrots and hummingbirds.

Even more striking is that the set of genes involved in each of those song innovations is remarkably similar to the genes involved in human speaking ability.

The findings are part of a package of eight scientific papers in a Dec. 12 special issue of Science and 21 additional papers appearing nearly simultaneously in Genome Biology, GigaScience and other journals. Jarvis' name appears on 20 papers and he is a corresponding author for 8 of them.

Jarvis co-led the Avian Phylogenomics Consortium with Guojie Zhang of the National Genebank at BGI in China and the University of Copenhagen and M. Thomas P. Gilbert of the Natural History Museum of Denmark. His Duke lab contributed to preparing samples, sequencing and annotating the genomes, performing the analyses and coordinating the overall project.

The Jarvis lab in the Bryan Research Building prepared DNA of many of the species, pulling it from little chunks of frozen, pink bird flesh collected over the past 30 years by museums and other institutions around the world. To ensure the DNA being sequenced really belonged to the Golden-collared manakin and not an undergraduate lab assistant, the lab has been kept spotlessly clean and many of its tools are used only once, to avoid the possibility of subsequent contamination.

"We change gloves a lot," said Carole Parent, the lab research analyst who set up a DNA isolation pipeline for the next stage of the project to sequence still more birds and supervised sample prep with a team of Duke undergrads and a student from East Chapel Hill High School.

All of this meticulous and somewhat tedious work has given Jarvis and hundreds of colleagues around the world a crack at an unprecedented amount of genomic data generated by BGI in China. The whole-genome comparison of the 48 bird species required new algorithms written at the University of Illinois and University of Texas that ran for 400 years of CPU time on three supercomputers in the U.S.

Of the 29 papers covering everything from penguin evolution to color vision, eight are devoted to bird song.

One of the Dec. 12 papers in Science found there is a consistent set of just over 50 genes that show higher or lower activity in the brains of vocal learning birds and humans. These changes were not found in the brains of birds that do not have vocal learning and of non-human primates that do not speak, according to this Duke team, which was led by Jarvis; Andreas Pfenning, a graduate of the Ph.D. program in computational biology and bioinformatics (CBB); and Alexander Hartemink, professor of computer science, statistical science and biology.

"This means that vocal learning birds and humans are more similar to each other for these genes in song and speech brain areas than other birds and primates are to them," Jarvis said.

These genes are involved in forming new connections between neurons of the motor cortex and neurons that control the muscles that produce sound.

A companion study by another CBB doctorate, Rui Wang, looked at the specialized activity of a pair of genes involved in the regions of the brain that control song and speech. This study, appearing in the Journal of Comparative Neurology, found that these genes are down- and up-regulated in one brain region of song-learning birds during the juvenile period of their vocal learning , changes that last into adulthood. This study, and that of Pfenning, hypothesize that changes in these genes could be critical for the evolution of song in birds and speech in humans.

"You can find those same genes in the genomes of all species, but they're active at much higher or lower levels in the specialized song or speech brain regions of vocal learning birds and humans," Jarvis said. "What this suggests to me is that when vocal learning evolves, there may be a limited way in which the brain circuits can evolve."

Another paper in Science from Duke, led by post-doc Osceola Whitney, Pfenning, Hartemink and Anne West, an associate professor of neurobiology, looked at gene activation in different areas of the brain during singing. This team found activation of 10 percent of the expressed genome during singing, with diverse activation patterns in different song-learning regions of the brain. The diverse gene patterns are best explained by epigenetic differences in the genomes of the different brain regions, meaning that individual cells in different brain regions can regulate genes at a moment's notice when the birds sing.

Among the three main groups of vocal learning birds, parrots are clearly different in their ability to mimic human speech. Mukta Chakraborty, a postdoc in the Jarvis lab, led a project that used the activity of some of the specialized genes to discover that the parrot's speech center is organized somewhat differently. It has what the researchers call a "song-system-within-a-song-system" in which the area of the brain with different gene activity for producing song has an outer ring of still more differences in gene expression.

Parrots are very social animals, Chakraborty said, and having the ability to quickly pick up "dialects" of parrot speech may account for their super-charged speech center. The "shell" or outer regions were found to be proportionally larger in the parrot species, which are believed to have the highest vocal, cognitive and social abilities. These species include Amazon parrots, the African Grey and the Blue and Gold Macaw.

Jarvis was also part of a team with Claudio Mello and his Ph.D. student Morgan Wirthlin at Oregon Health & Science University that found ten more genes that are unique to song-control regions of songbirds. This paper appears in BMC Genomics.

A paper in Science led by Zhang, Gilbert and Jarvis found the genomes of vocal learners are more rapidly evolving and have more chromosomal rearrangements compared to other bird species. This genomic comparison also found similar changes occurred independently in in the song-learning area of different birds' brains.

Jarvis said knowing more of this history of how speech evolved in birds makes vocal learning birds even more valuable model organisms for helping to answer the questions he and other researchers are addressing about human speech.

"Speech is difficult to study in human brains," he said. "Whales and elephants learn speech and songs, but they're too big to house in the lab. Now that we have a deeper understanding of how similar birdsong brain regions are to human speech regions at the genetic level, I think they'll be a better model than ever."

Jarvis' general exploration of the bird brain over his 16 years at Duke has also led to several unexpected discoveries unrelated to song.

In 2005, he and colleagues found a center of the brain in migratory birds that apparently enables sensing of magnetic fields through "night vision." That year he also led a revision of the understanding of bird brain organization and vertebrate brain evolution. Last year, he led a re-drawing of the geography of the bird brain based on analysis of 52 genes that are active in 23 areas of the brains of eight species of birds. This new map shows neuron groupings in the birds' brains to be organized in columns like the brains of humans and other mammals.

He also branched out a bit and learned about the brain structures that enable mice to "sing" in ultrasonic ranges beyond human hearing.

Jarvis said this first wave of findings from the Avian Phylogenomics Consortium is just the beginning of an exciting new era of genomic analysis. The international group is already sequencing more birds at the whole-genome level.

"This is an exciting moment," said Jarvis, who is also a member of the Duke Institute for Brain Sciences. "Lots of fundamental questions now can be resolved with more genomic data from a broader sampling. I got into this project because of my interest in birds as a model for vocal learning and speech production in humans, and it has opened up some amazing new vistas on brain evolution."

Source: Duke University

Researchers ferret out a flu clue

Professor Michael Jennings, Deputy Director of the Institute for Glycomics. Credit: Image courtesy of Griffith University

Research that provides a new understanding as to why ferrets are similar to humans is set to have major implications for the development of novel drugs and treatment strategies.

Published in the journal Nature Communications, the research is a collaboration between Professor Michael Jennings and other researchers from the Institute for Glycomics, Griffith University and collaborators at the University of Queensland and the University of Adelaide.

The team has shown for the first time that ferrets share a mutation that was previously thought to be unique to humans, among the mammals. This helps to explain why the molecular characteristics of ferrets so uniquely mimic human susceptibility, severity and transmission of influenza A virus strains.

Professor Michael Jennings, Deputy Director of the Institute for Glycomics, says these findings open up a completely novel approach to tackling human diseases from influenza through to cancer.

"For over 80 years we've known that ferrets are uniquely susceptible to human influenza A virus, but the precise reason was unknown," Professor Jennings said.

"We have shown that ferrets have a mutation in a gene required to make a crucial sugar called sialic acid. Most animals can make two types of sialic acid. Ferrets, like humans can make only one. Different flu strains have preferences for the type of sialic acid they bind to cause infection. Because ferrets can only make the human form of this sugar, they are naturally "humanized" for the receptors recognised by human strains of the flu virus."

Source: Griffith University

Flu virus key machine: First complete view of structure revealed

The complete structure allows researchers to understand how the polymerase uses host cell RNA (red) to kick-start the production of viral messenger RNA. Credit: © EMBL/P.Riedinger

Scientists looking to understand -- and potentially thwart -- the influenza virus now have a much more encompassing view, thanks to the first complete structure of one of the flu virus' key machines. The structure, obtained by scientists at EMBL Grenoble, allows researchers to finally understand how the machine works as a whole, and could prove instrumental in designing new drugs to treat serious flu infections and combat flu pandemics.

If you planned to sabotage a factory, a recon trip through the premises would probably be much more useful than just peeping in at the windows. Scientists looking to understand -- and potentially thwart -- the influenza virus have now gone from a similar window-based view to the full factory tour, thanks to the first complete structure of one of the flu virus' key machines. The structure, obtained by scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, allows researchers to finally understand how the machine works as a whole. Published in two papers in Nature, the work could prove instrumental in designing new drugs to treat serious flu infections and combat flu pandemics.

The machine in question, the influenza virus polymerase, carries out two vital tasks for the virus. It makes copies of the virus' genetic material -- the viral RNA -- to package into new viruses that can infect other cells; and it reads out the instructions in that genetic material to make viral messenger RNA, which directs the infected cell to produce the proteins the virus needs. Scientists -- including Cusack and collaborators -- had been able to determine the structure of several parts of the polymerase in the past. But how those parts came together to function as a whole, and how viral RNA being fed in to the polymerase could be treated in two different ways remained a mystery.

"The flu polymerase was discovered 40 years ago, so there are hundreds of papers out there trying to fathom how it works. But only now that we have the complete structure can we really begin to understand it," says Stephen Cusack, head of EMBL Grenoble, who led the work.

Using X-ray crystallography, performed at the European Synchrotron Radiation Facility (ESRF) in Grenoble, Cusack and colleagues were able to determine the atomic structure of the whole polymerase from two strains of influenza: influenza B, one of the strains that cause seasonal flu in humans, but which evolves slowly and therefore isn't considered a pandemic threat; and the strain of influenza A -- the fast-evolving strain that affects humans, birds and other animals and can cause pandemics -- that infects bats.

"The high-intensity X-ray beamlines at the ESRF, equipped with state-of-the-art Dectris detectors, were crucial for getting high quality crystallographic data from the weakly diffracting and radiation sensitive crystals of the large polymerase complex," says Cusack. "We couldn't have got the data at such a good resolution without them."

The structures reveal how the polymerase specifically recognises and binds to the viral RNA, rather than just any available RNA, and how that binding activates the machine. They also show that the three component proteins that make up the polymerase are very intertwined, which explains why it has been very difficult to piece together how this machine works based on structures of individual parts.

Although the structures of both viruses' polymerases were very similar, the scientists found one key difference, which showed that one part of the machine can swivel around to a large degree. That ability to swivel explains exactly how the polymerase uses host cell RNA to kick-start the production of viral proteins. The swivelling component takes the necessary piece of host cell RNA and directs it into a slot leading to the machine's heart, where it triggers the production of viral messenger RNA.

Now that they know exactly where each atom fits in this key viral machine, researchers aiming to design drugs to stop influenza in its tracks have a much wider range of potential targets at their disposal -- like would-be saboteurs who gain access to the whole production plant instead of just sneaking looks through the windows. And because this is such a fundamental piece of the viral machinery, not only are the versions in the different influenza strains very similar to each other, but they also hold many similarities to their counterparts in related viruses such as lassa, hanta, rabies or ebola.

The EMBL scientists aim to explore the new insights this structure provides for drug design, as well as continuing to try to determine the structure of the human version of influenza A, because although the bat version is close enough that it already provides remarkable insights, ultimately fine-tuning drugs for treating people would benefit from/require knowledge of the version of the virus that infects humans. And, since this viral machine has to be flexible and change shape to carry out its different tasks, Cusack and colleagues also want to get further snapshots of the polymerase in different states.

"This doesn't mean we now have all the answers," says Cusack, "In fact, we have as many new questions as answers, but at least now we have a solid basis on which to probe further."

Source: European Molecular Biology Laboratory (EMBL)

Study may help slow the spread of flu

A false color image of an influenza virus particle, or “virion.” Credit: Centers for Disease Control/Cynthia Goldsmith

An important study conducted in part at the Department of Energy's SLAC National Accelerator Laboratory may lead to new, more effective vaccines and medicines by revealing detailed information about how a flu antibody binds to a wide variety of flu viruses.

The flu virus infects millions of people each year. While for most this results in an unproductive and uncomfortable week or two, the flu also contributes to many deaths in the average flu season. And while vaccines are effective in preventing the flu, they require almost yearly reformulation to keep up with the constantly changing virus.

At SSRL and APS, a team of researchers from The Scripps Research Institute, Fujita Health University and Osaka University studied both samples of flu virus components and an anti-flu antibody. The antibody, called F045-092, was already known to neutralize the flu by connecting to the region of the flu virus that binds to host cells, so it can no longer bind to its target and cause infection.

"There are patches of the virus that are more hypervariable than others," said Peter Lee, a postdoctoral research associate at The Scripps Research Institute and first author of the paper. "But the flu always binds to host cells within the same region, and so that binding site needs to be functionally conserved. That makes it a site of vulnerability."

The team used the X-ray beams at SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) and Argonne National Laboratory's Advanced Photon Source (APS), both DOE Office of Science User Facilities, to view the structure of the antibody bound to one subtype of the flu virus called H3N2. They discovered that the antibody inserts a loop into the binding site of the virus, which would otherwise attach to a receptor in a host cell. Additional experimental data showed that F045-092 binds a wide variety of strains and subtypes, including all H3 avian and human viruses from 1963 to 2011 that were tested.

This understanding of the antibody's structural details and binding modes offers new insight for future structure-based drug discovery and novel avenues for designing future vaccines.
But the only way to achieve those goals is for many groups of scientists to work together, Lee said. "Our lab is very focused on the structure of the virus and antibodies, while there are lots of other labs focused on everything from small protein design to vaccine design," he said. "Hopefully we can use this structural information and join together as one big team to tackle the flu."

Source: SLAC National Accelerator Laboratory

Flu at the zoo and other disasters: Experts help animal exhibitors prepare for the worst

After experiencing power outages during a 2007 ice storm in Springfield, Mo., Dickerson Park Zoo officials improved their backup power and heating systems to keep animals -- like Henry, pictured here -- safe and warm. Credit: Dickerson Park Zoo

Here are three disaster scenarios for zoo or aquarium managers: One, a wildfire lunges towards your facility, threatening your staff and hundreds of zoo animals. Two, hurricane floodwaters pour into your basement, where thousands of exotic fish and marine mammals live in giant tanks. Three, local poultry farmers report avian influenza (bird flu) in their chickens, a primary source of protein for your big cats.

What do you do?

These are among the many potential disasters the managers of zoos and aquariums ponder in their emergency preparedness drills and plans. But these stories are not just worst-case scenarios: The events described above actually happened, and the aftermath -- often heroic, and sometimes tragic -- depended in large part on the institutions' preparedness training, planning and forethought in calmer times.

When bad weather strikes or illness invades, zoos and aquariums are among the most vulnerable facilities affected, said University of Illinois veterinarian Yvette Johnson-Walker, a clinical epidemiologist who contributes to emergency response training efforts at animal exhibitor institutions. She is a clinical instructor in the department of veterinary clinical medicine at Illinois, and lead author of a new paper on emergency preparedness at zoos and aquariums in the journal Homeland Security & Emergency Management.

Some animals are likely to suffer if the electricity goes out for long, she said. Others are large, skittish and dangerous under normal conditions.

Training caretakers and keepers to minimize their own risks while attending to their animals in an emergency is a challenge, but leads to the best outcomes, she said.

In 2012, Johnson-Walker joined forces with Yvonne Nadler, a project manager with the Zoo and Aquarium All Hazards Preparedness Response and Recovery Center, to bring vital emergency training to accredited animal exhibitor institutions in Illinois, Indiana and Missouri. This effort, funded by the U.S. Department of Agriculture and supported by the Association of Zoos & Aquariums, has since expanded, providing training to staff from zoos and aquariums in 23 states.

The trainings, dubbed "Flu at the Zoo," focus on avian influenza, a viral disease that spread in the 2000s among wild and captive birds and also infected hundreds of people, primarily in Asia, Africa and the Middle East. Bird flu serves as a useful model scenario to help train participants in basic preparedness skills.

One such skill is familiarity with the Incident Command System (ICS), a framework developed by firefighters and adopted by the Federal Emergency Management Agency (FEMA) that allows first responders to quickly set up their emergency response operation and assign vital tasks. The ICS has long been used by public safety, law enforcement and public health entities involved in emergency response.

"We wanted zoos and aquariums to have a seat at the table when there's planning for how we're going to respond to emergencies, and to be able to fit into the system, know who to talk to and how to communicate," Johnson-Walker said.

It's also important to recognize the other responders and understand their roles, she said. If the event involves a disease like bird flu, the USDA, FEMA, National Institutes of Health, state veterinarian, state and federal wildlife services, public health authorities, veterinary organizations, police, hospitals and perhaps even local poultry operations will be involved in the response. Knowing who does what can speed communication in a crisis.

Planning also helps managers make best use of the limited supplies or equipment they have on hand, Nadler said.

"There are certain types of livestock trailers, for example, that can be adapted to moving big cats," she said. "Is that your preferred method of movement? Of course it isn't, but in an emergency that might be your only option."

One beneficiary of the emergency training, Melinda Arnold, knows firsthand the value of preparedness. Arnold is public relations director for Friends of the Zoo, affiliated with Dickerson Park Zoo in Springfield, Missouri. The zoo suffered a blackout during a 2007 ice storm that shut off power for most of the city for several days.

"We did have backup generators," Arnold said. "The greatest problem with the generators was that those fueling stations in town that did have gas didn't have power, so they couldn't pump the gas."

Zoo staff had to travel many miles outside of the affected area with gas cans to collect gas to run the backup generators, she said.

"Now we have some propane-powered backups," Arnold said.

A more recent incident at the zoo, the accidental death of a zookeeper in 2013, caused Dickerson Park Zoo officials to re-evaluate all of their safety protocols. Even though the zookeeper had decades of experience and was guarded by a protective barrier, a skittish elephant rushed him at an unguarded moment, and he fell and was trampled to death.
"It made us step back, not only in our elephant management but in all areas of the zoo, and look at our safety procedures and points of contact with dangerous animals and evaluate those safety conditions and make improvements," Arnold said.

The preparedness plans, drills, discussions and training all help zoos and aquariums reassess their procedures, even those that seem to be safe after decades of operations and no major incidents, she said.

Source: University of Illinois at Urbana-Champaign

'Big Bang' of bird evolution mapped: Genes reveal deep histories of bird origins, feathers, flight and song

Crocodiles are the closest living relatives of birds, sharing a common ancestor that lived around 240 million years ago and also gave rise to the dinosaurs.
Credit: Stephen J. O'Brien, Avian Phylogenomics Group

The genomes of modern birds tell a story of how they emerged and evolved after the mass extinction that wiped out dinosaurs and almost everything else 66 million years ago. That story is now coming to light, thanks to an ambitious international collaboration that has been underway for four years.

The first findings of the Avian Phylogenomics Consortium are being reported nearly simultaneously in 29 papers -- eight papers in a Dec. 12 special issue of Science and 21 more in Genome Biology, GigaScience and other journals.

Scientists already knew that the birds who survived the mass extinction experienced a rapid burst of evolution. But the family tree of modern birds has confused biologists for centuries and the molecular details of how birds arrived at the spectacular biodiversity of more than 10,000 species is barely known.

To resolve these fundamental questions, a consortium led by Guojie Zhang of the National Genebank at BGI in China and the University of Copenhagen, Erich D. Jarvis of Duke University and the Howard Hughes Medical Institute and M. Thomas P. Gilbert of the Natural History Museum of Denmark, has sequenced, assembled and compared full genomes of 48 bird species. The species include the crow, duck, falcon, parakeet, crane, ibis, woodpecker, eagle and others, representing all major branches of modern birds.

"BGI's strong support and four years of hard work by the entire community have enabled us to answer numerous fundamental questions to an unprecedented scale," said Guojie Zhang. "This is the largest whole genomic study across a single vertebrate class to date. The success of this project can only be achieved with the excellent collaboration of all the consortium members."

"Although an increasing number of vertebrate genomes are being released, to date no single study has deliberately targeted the full diversity of any major vertebrate group," added Tom Gilbert. "This is precisely what our consortium set out to do. Only with this scale of sampling can scientists truly begin to fully explore the genomic diversity within a full vertebrate class."

"This is an exciting moment," said neuroscientist Erich Jarvis. "Lots of fundamental questions now can be resolved with more genomic data from a broader sampling. I got into this project because of my interest in birds as a model for vocal learning and speech production in humans, and it has opened up some amazing new vistas on brain evolution."

This first round of analyses suggests some remarkable new ideas about bird evolution. The first flagship paper published in Science presents a well-resolved new family tree for birds, based on whole-genome data. The second flagship paper describes the big picture of genome evolution in birds. Six other papers in the special issue of Science describe how vocal learning may have independently evolved in a few bird groups and in the human brain's speech regions; how the sex chromosomes of birds came to be; how birds lost their teeth; how crocodile genomes evolved; ways in which singing behavior regulates genes in the brain; and a new method for phylogenic analysis with large-scale genomic data.

The Avian Phylogenomics Consortium has so far involved more than 200 scientists hailing from 80 institutions in 20 countries, including the BGI in China, the University of Copenhagen, Duke University, the University of Texas at Austin, the Smithsonian Museum, the Chinese Academy of Sciences, Louisiana State University and many others.

A Clearer Picture of the Bird Family Tree
Previous attempts to reconstruct the avian family tree using partial DNA sequencing or anatomical and behavioral traits have met with contradiction and confusion. Because modern birds split into species early and in such quick succession, they did not evolve enough distinct genetic differences at the genomic level to clearly determine their early branching order, the researchers said. To resolve the timing and relationships of modern birds, the consortium authors used whole-genome DNA sequences to infer the bird species tree.

"In the past, people have been using 10 to 20 genes to try to infer the species relationships," Jarvis said. "What we've learned from doing this whole-genome approach is that we can infer a somewhat different phylogeny [family tree] than what has been proposed in the past. We've figured out that protein-coding genes tell the wrong story for inferring the species tree. You need non-coding sequences, including the intergenic regions. The protein coding sequences, however, tell an interesting story of proteome-wide convergence among species with similar life histories."

This new tree resolves the early branches of Neoaves (new birds) and supports conclusions about some relationships that have been long-debated. For example, the findings support three independent origins of waterbirds. They also indicate that the common ancestor of core landbirds, which include songbirds, parrots, woodpeckers, owls, eagles and falcons, was an apex predator, which also gave rise to the giant terror birds that once roamed the Americas.

The whole-genome analysis dates the evolutionary expansion of Neoaves to the time of the mass extinction event 66 million years ago that killed off all dinosaurs except some birds. This contradicts the idea that Neoaves blossomed 10 to 80 million years earlier, as some recent studies suggested.
Based on this new genomic data, only a few bird lineages survived the mass extinction. They gave rise to the more than 10,000 Neoaves species that comprise 95 percent of all bird species living with us today. The freed-up ecological niches caused by the extinction event likely allowed rapid species radiation of birds in less than 15 million years, which explains much of modern bird biodiversity.
Increasingly sophisticated and more affordable genomic sequencing technologies and the advent of computational tools for reconstructing and comparing whole genomes have allowed the consortium to resolve these controversies with better clarity than ever before, the researchers say.

With about 14,000 genes per species, the size of the datasets and the complexity of analyzing them required several new approaches to computing evolutionary family trees. These were developed by computer scientists Tandy Warnow at the University of Illinois at Urbana-Champaign, Siavash Mirarab, a student at the University of Texas at Austin and Alexis Stamatakis at the Heidelburg Institute for Theoretical Studies. Their algorithms required the use of parallel processing supercomputers at the Munich Supercomputing Center (LRZ), the Texas Advanced Computing Center (TACC) and the San Diego Supercomputing center (SDSC).

"The computational challenges in estimating the avian species tree used around 300 years of CPU time, and some analyses required supercomputers with a terabyte of memory," Warnow said.
The bird project also had support from the Genome 10K Consortium of Scientists (G10K), an international science community working toward rapidly assessing genome sequences for 10,000 vertebrate species.

"The Avian Genomics Consortium has accomplished the most ambitious and successful project that the G10K Project has joined or endorsed," said G10K co-leader Stephen O'Brien, who co-authored a commentary on the bird sequencing project appearing in GigaScience.

A Genomic Perspective of Avian Evolution and Biodiversity
For all their biological intricacies, birds are surprisingly light on DNA. A study led by Zhang, Cai Li and the consortium authors found that compared to other reptile genomes, avian genomes contain fewer of the repeating sequences of DNA and lost hundreds of genes in their early evolution after birds split from other reptiles.

"Many of these genes have essential functions in humans, such as in reproduction, skeleton formation and lung systems," Zhang said. "The loss of these key genes may have a significant effect on the evolution of many distinct phenotypes of birds. This is an exciting finding, because it is quite different from what people normally think, which is that innovation is normally created by new genetic material, not the loss of it. Sometimes, less is more."

From the whole chromosome level to the order of genes, this group found that the genomic structure of birds has stayed remarkably the same among species for more than 100 million years. The rate of gene evolution across all bird species is also slower compared to mammals.

Yet some genomic regions display relatively faster evolution in species with similar lifestyles or phenotypes, such as involving vocal learning. This pattern of what is called convergent evolution may be the underlying mechanism that explains how distant bird species evolved similar phenotypes independently. Zhang said these analyses on particular gene families begin to explain how birds evolved a lighter skeleton, a distinct lung system, dietary specialties, color vision, as well as colorful feathers and other sex-related traits.

Important Lessons

The new studies have shed light on several other questions about birds, including:
How did vocal learning evolve?  Eight studies in the package examined the subject of vocal learning. According to new evidence in the two flagship papers, vocal learning evolved independently at least twice, and was associated with convergent evolution in many proteins. A Science study led by Andreas Pfenning, Alexander Hartemink, Jarvis and others at Duke, in collaboration with researchers at the Allen Institute for Brain Science in Seattle and the RIKEN Institute in Japan, found that the specialized song-learning brain circuitry of vocal learning birds (songbirds, parrots and hummingbirds) and human brain speech regions have convergent changes in the activity of more than 50 genes. Most of these genes are involved in forming neural connections. Osceola Whitney, Pfenning and Anne West, also of Duke, found in another Science study that singing is associated with the activation of 10 percent of the expressed genome, with diverse activation patterns in different song-learning regions of the brain, controlled by epigenetic regulation of the genome. Duke's Mukta Chakraborty and others found in a PLoS ONE study that parrots have a song system within a song system, with the surrounding song system unique to them. This might explain their greater ability to imitate human speech. In a BMC Genomics study, Morgan Wirthlin, Peter Lovell and Claudio Mello from Oregon Health & Science University found unique genes in the song-control brain regions of songbirds.

The XYZW of sex chromosomes. Just as the sex of humans is determined by the X and Y chromosomes, the sex of birds is controlled by the Z and W chromosomes. The W makes birds female, just as the Y makes humans male. Most mammals share a similar evolutionary history of the Y chromosome, which now contains many degenerated genes that no longer function and only a few active genes related to "maleness." A Science study led by Qi Zhou and Doris Bachtrog from the University of California, Berkeley, and Zhang found that half of bird species still contain substantial numbers of active genes in their W chromosomes. This challenges the classic view that the W chromosome is a "graveyard of genes" like the human Y.

This group also found that bird species are at drastically different states of sex chromosome evolution. For example, the ostrich and emu, which belong to one of the older branches of the bird family tree, have sex chromosomes resembling their ancestors. Yet some modern birds such as the chicken and zebra finch have sex chromosomes that contain few active genes. This opens a new set of questions on how the diversity of sex chromosomes may drive the diversity of sex differences in the outward appearance of various bird species. Peacocks and peahens are dramatically different; male and female crows are indistinguishable.

How did birds lose their teeth? In a Science study led by Robert Meredith from Montclair State University and Mark Springer from the University of California, Riverside, a comparison between the genomes of living bird species and those of vertebrate species that have teeth identified key mutations in the parts of the genome that code for enamel and dentin, the building blocks of teeth. The evidence suggests that five tooth-related genes were disabled within a short time period in the common ancestor of modern birds more than 100 million years ago.

What's the connection between birds and dinosaurs? Unlike mammals, birds (along with reptiles, fish and amphibians) have a large number of tiny microchromosomes. These smaller packages of gene-rich material are thought to have been present in their dinosaur ancestors. A study of genome karyotype structure in BMC Genomics analyzed whole genomes of the chicken, turkey, Peking duck, zebra finch and budgerigar. It found the chicken has the most similar overall chromosome pattern to an avian ancestor, which was thought to be a feathered dinosaur. This work was led by Darren Griffin and Michael Romanov from the University of Kent, and by Dennis Larkin and Marta Farré from the Royal Veterinary College, University of London.

Another study in Science examined birds' closest living relatives, the crocodiles. This team, led by Ed Green and Benedict Paton from the University of California, Santa Cruz, David Ray from Texas Tech University and Ed Braun from the University of Florida, found that crocodiles have one of the slowest-evolving genomes. The researchers were able to infer the genome sequence of the common ancestor of birds and crocodilians (archosaurs) and therefore all dinosaurs, including those that went extinct 66 million years ago.

Do differences in gene trees versus species trees matter? In the phylogenomics flagship study by Jarvis and others, the consortium found that no gene tree has a history exactly the same as the species tree, partly due to a process called incomplete lineage sorting. Another Science study, led by Tandy Warnow at the University of Texas and the University of Illinois, and her student Siavash Mirarab, developed a new computational approach called "statistical binning." They used this approach to show it does not matter much that the gene trees differ from the species tree because they were able to infer the first coalescent-based, genome-scale species tree, combining gene trees with similar histories to accurately infer a species tree.

Do bird genomes carry fewer virus sequences than other species? Mammalian genomes harbor a diverse set of genomic "fossils" of past viral infections called "endogenous viral elements" (EVEs). A study published in Genome Biology led by Jie Cui of Duke-NUS Graduate Medical School in Singapore, Edward Holmes of the University of Sydney and Zhang, found that bird species had 6-13 times fewer EVE infections in their past than mammals. This finding is consistent with the fact that birds have smaller genomes than mammals. It also suggests birds may either be less susceptible to viral invasions or better able to purge viral genes.

When did colorful feathers evolve? Elaborate, colorful feathers are thought to be evolutionarily advantageous, giving a male bird in a given species an edge over his competitors when it comes to mating. Zhang's flagship paper in Science, which is further analyzed by Matthew Greenwold and Roger Sawyer from the University of South Carolina in a companion study in BMC Evolutionary Biology, found that genes involved in feather coloration evolved more quickly than other genes in eight of 46 bird lineages. Waterbirds have the lowest number of beta keratin feather genes, landbirds have more than twice as many, and in domesticated pet and agricultural bird species, there are eight times more of these genes.

What happens to species facing extinction or recovering from near-extinction? Birds are like the proverbial canaries in the coal mine because of their sensitivity to environmental changes that cause extinction. In a Genome Biology study led by Shengbin Li, Cheng Cheng and Jun Yu from Xi'an Jiaotong University and Jarvis, researchers analyzed the genomes of species that have recently gone nearly extinct, including the crested ibis in Asia and the bald eagle in the Americas. They found genes that break down environmental toxins have a higher rate of mutations in these species and there is lower diversity of immune system genes in endangered species. In a recovering crested ibis population, genes involved in brain function and metabolism are evolving more rapidly. The researchers found more genomic diversity in the recovering population than was expected, giving greater hope for species conservation.

The Start of Something Bigger
This sweeping genome-level comparison of an entire class of life is being powered by frozen bird tissue samples collected over the past 30 years by museums and other institutions around the world. Samples are sent as fingernail-sized chunks of frozen flesh mostly to Duke University and University of Copenhagen for DNA separation. Most of the genome sequencing and critical initial analyses of the genomes have then been conducted by the BGI in China.

The avian genome consortium is now creating a database that will be made publicly available in the future for scientists to study the genetic basis of complex avian traits.

Setting up the pipeline for the large-scale study of whole genomes -- collecting and organizing tissue samples, extracting the DNA, analyzing its quality, sequencing and managing torrents of new data -- has been a massive undertaking. But the scientists say their work should help inform other major efforts for the comprehensive sequencing of vertebrate classes. To encourage other researchers to dig through this 'big data' and discover new patterns that were not seen in small-scale data before, the avian genome consortium has released the full dataset to the public in GigaScience, and in NCBI, ENSEMBL and CoGe databases.

Under the leadership of Dave Burt, the National Avian Research Facility at the Roslin Institute and Edinburgh University, UK, has created genome browser databases based on the ENSEMBL model for 48 species.

Source: Duke University