New Genome Sequences Reveal the Bird Tree of Life

A global, four-year project involving hundreds of scientists shows how avian lineages diverged after the dinosaurs’ extinction.

ERIC JARVIS DESCRIBES HOW THE MASSIVE AVIAN GENOME PROJECT REVEALED KEY RELATIONSHIPS AND EVENTS WITHIN BIRD EVOLUTION. | AAAS/ CARLA SCHAFFER

An international team of researchers has sequenced the genomes of 45 avian species and created the most reliable tree of life for birds to date. Their new avian family tree helps to clarify how modern birds — the most species-rich class of four-limbed vertebrates on the planet — emerged rapidly from a mass extinction event that wiped out the dinosaurs about 66 million years ago.

It also reveals how some of the earliest branches on the bird tree of life diverged, answering many long-standing questions about the common ancestor of birds, crocodilians, and dinosaurs. The findings shed new light on the evolution of avian sex chromosomes, vocal learning in both birds and humans, and the process that led to birds losing their teeth.

The massive comparative genomics project took more than four years to complete and involved hundreds of scientists from about 80 institutions in 20 different countries. The collaboration culminated in multiple studies, eight of which are published in the 12 December issue of Science. Others are published in journals such as Genome Biology and GigaScience.

The research was led by

• Guojie Zhang from BGI in Shenzhen, China, and the University of Copenhagen in Denmark; 
• Erich Jarvis from the Howard Hughes Medical Institute and Duke University in Durham, North Carolina; and 
• Thomas Gilbert from the Natural History Museum of Denmark and Curtin University in Australia. 

With the expertise of colleagues from around the world, they were able to sequence at least one genome from every major modern bird lineage.

Zhang and his colleagues described their analysis of 48 avian genomes, including the 45 new sequences that they contributed (crow, duck, pigeon, falcon, woodpecker, eagle, ostrich, and many more) along with three genomes that were already available (chicken, turkey, and zebra finch). Their findings help to explain why bird genomes, in general, are about 70% smaller than those of mammals.

BIRD SPECIMENS FROM THE NATIONAL MUSEUM OF NATURAL HISTORY IN WASHINGTON, D.C. ILLUSTRATE SOME OF THE DIVERSE AVIAN SPECIES WHOSE GENOMES WERE SEQUENCED FOR THE PROJECT. | AAAS/ CARLA SCHAFFER

"One major reason that bird genomes are so small is because they don't have much repetitive DNA," explained Zhang during a webcast teleconference. "Another reason is that bird genomes have experienced massive gene loss in their ancestral stages. At least 1,600 genes have been lost in all bird genomes. Many of these genes actually have essential functions in humans, including some related to reproduction, skeleton formation, and lung systems."

"The loss of these key genes may have a significant effect on the evolution of many distinct phenotypes of birds," he continued. "Like their loss of teeth and dysfunction of one of their ovaries."

The analysis also revealed that the earliest common ancestor of land birds, which include parrots and songbirds as well as hawks and eagles, was a predator at the top of its food chain.

In a separate report, Jarvis and colleagues showed that protein-coding genes are not enough to get accurate phylogenetic trees. They suggested that researchers must include non-coding sequences of DNA as well as regions between the genes to provide a more accurate picture.

"In the past, people have been using one, two — up to 10 or 20 genes — to try to infer [bird] species relationships over the last 100 million years or so," said Jarvis. "Our theory has been: If you take the whole genome, you would have a more accurate species tree than just one or two genes [could provide] alone."

Their approach required more than 300 years of CPU time on several supercomputers, but they suggest that it could enable other groups of researchers to reconstruct similar, high-quality species trees for other challenging datasets in the future.

Ed Green from the University of California in Santa Cruz, California, and colleagues described the first sequencing of three crocodilian genomes — the American alligator, the saltwater crocodile, and the Indian gharial — which represent birds' closest living relatives. They revealed that the genomes of such crocodilians are evolving at an exceptionally slow pace.

THE INDIAN GHARIAL IS ONE OF THE CLOSEST LIVING RELATIVES OF BIRDS. | CHRISTOPHER BROCHU

"The molecular evolution of birds is much faster than it is in crocs, turtles, and other reptilian lineages," said Green. "So this avian lineage seems to be faster than other reptiles, but not faster than mammals."

Some of the other Science reports explore long-standing mysteries of bird biology. Qi Zhou from the University of California in Berkeley, California, and colleagues, for example, used the new avian genome sequences to explain how sex chromosomes have evolved in birds. Unlike the human Y chromosome, the avian W chromosome still has many active genes, and sex chromosomes of various bird species are currently at different stages of evolution, they write.

READ MORE ABOUT

THE NEW BIRD FAMILY TREE

SCIENCE AVIAN GENOME

Andreas Pfenning from Duke University with support from the Howard Hughes Medical Institute, along with his colleagues, exploited the sequences to study the molecular specializations between brain circuits that are important for singing in vocal-learning birds and speech in humans. Osceola Whitney, also from Duke University, and his colleagues determined that a whopping 10% of a bird's genome is regulated by singing, with highly diverse patterns across singing brain regions mediated by differences in gene expression.

Robert Meredith from Montclair State University in Montclair, New Jersey, and colleagues suggests that the mutations that eliminated enamel and dentin from the teeth of modern birds, an event which eventually led to toothless beaks-began about 116 million years ago.

Taken together, these reports support the theory of a "big bang" for bird evolution, with many species emerging rapidly during the 10 to 15 million years that followed the dinosaurs' extinction at the Cretaceous-Paleogene Boundary. They're poised to provide a model for other comparative genomics projects for the foreseeable future.

ORIGINAL: AAAS

Brandon Bryn

Natasha D. Pinol

11 December 2014

The Brain’s Inner Language

Video|2:25 Credit Probing the Parliament of Neurons Clay Reid and colleagues are going deep into

SEATTLE — When Clay Reid decided to leave his job as a professor at Harvard Medical School to become a senior investigator at the Allen Institute for Brain Science in Seattle in 2012, some of his colleagues congratulated him warmly and understood right away why he was making the move.

Others shook their heads. He was, after all, leaving one of the world’s great universities to go to the academic equivalent of an Internet start-up, albeit an extremely well- financed, very ambitious one, created in 2003 by Paul Allen, a founder of Microsoft.

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Mapping the Highways of the Brain
Deanna Barch and her colleagues are trying to map connections in the human brain. The study is part of the Human Connectome Project.

Still, “it wasn’t a remotely hard decision,” Dr. Reid said. He wanted to mount an all-out investigation of a part of the mouse brain. And although he was happy at Harvard, the Allen Institute offered not only great colleagues and deep pockets, but also an approach to science different from the classic university environment. The institute was already mapping the mouse brain in fantastic detail, and specialized in the large-scale accumulation of information in atlases and databases available to all of science. Photo

When neurons in the brain of a live mouse, top, are active, they flash brightly. Dr. Clay Reid, above left, and colleagues at the Allen Institute for Brain Science are working with mice to better understand the human mind. Above center, areas of the mouse cortex related to vision, and connected to other parts involving visual perception. Credit Zach Wise for The New York Times

Now, it was expanding, and trying to merge its semi-industrial approach to data gathering with more traditional science driven by individual investigators, by hiring scientists like Christof Koch from the California Institute of Technology as chief scientific officer in 2011 and Dr. Reid. As a senior investigator, he would lead a group of about 100, and work with scientists, engineers and technicians in other groups.

Without the need to apply regularly for federal grants, Dr. Reid could concentrate on one piece of the puzzle of how the brain works. He would try to decode the workings of one part of the mouse brain, the million neurons in the visual cortex, from, as he puts it, “molecules to behavior.”

There are many ways to map the brain and many kinds of brains to map. Although the ultimate goal of most neuroscience is understanding how human brains work, many kinds of research can’t be done on human beings, and the brains of mice and even flies share common processes with human brains.

The work of Dr. Reid, and scientists at Allen and elsewhere who share his approach, is part of a surge of activity in brain research as scientists try to build the tools and knowledge to explain — as well as can ever be explained — how brains and minds work. Besides the Obama administration’s $100 million Brain Initiative and the European Union’s $1 billion, decade-long Human Brain Project, there are numerous private and public research efforts in the United States and abroad, some focusing on the human brain, others like Dr. Reid’s focusing on nonhumans.

While the Human Connectome Project, which is spread among several institutions, aims for an overall picture of the associations among parts of the human brain, other scientific teams have set their sights on drilling to deeper levels. For instance, the Connectome Project at Harvard is pursuing a structural map of the mouse brain at a level of magnification that shows packets of neurochemicals at the tips of brain cells.

At Janelia Farm, the Virginia research campus of the Howard Hughes Medical Institute, researchers are aiming for an understanding of the complete fly brain — a map of sorts, if a map can be taken to its imaginable limits, including structure, chemistry, genetics and activity.

“I personally am inspired by what they’re doing at Janelia,” Dr. Reid said.

All these efforts start with maps and enrich them. If Dr. Reid is successful, he and his colleagues will add what you might call the code of a brain process, the language the neurons use to store, transmit and process information for this function.

Not that this would be any kind of final answer. In neuroscience, perhaps more than in most other disciplines, every discovery leads to new questions.

“With the brain,” Dr. Reid said, “you can always go deeper.”

‘Psychoanalyst’s Kid Probes Brain!’ Photo

A diamond-tipped slicer is used to prepare a piece of a mouse’s brain for examination with a modified electron microscope at the Allen Institute. Credit Zach Wise for The New York Times

Dr. Reid, 53, grew up in Boston, in a family with deep roots in medicine. His grandfather taught physiology at Harvard Medical School. “My parents were both psychoanalysts,” he said during an interview last fall, smiling as he imagined a headline for this article, “Psychoanalyst’s Kid Probes Brain!”

“I pretty much always knew that I wanted to be a scientist,” he said.

As an undergraduate at Yale, he majored in physics and philosophy and in mathematics, but in the end decided he didn’t want to be a physicist. Biology was attractive, but he was worried enough about his mathematical bent to talk to one of his philosophy professors about concerns that biology would too fuzzy for him.

The professor had some advice. “You really should read Hubel and Wiesel,” he said, referring to David Hubel and Torsten Wiesel, who had just won the Nobel Prize in 1981 for their work showing how binocular vision develops in the brain.

He read their work, and when he graduated in 1982, he was convinced that the study of the brain was both hard science and a wide-open field. He went on to an M.D.-Ph.D. program at Cornell Medical College and Rockefeller University, where Dr. Wiesel had his lab (he would go on to be president of Rockefeller).

As his studies progressed, Dr. Reid began to have second thoughts about pursuing medicine rather than research. Just a week before he was to commit to a neurology residency, he said, “I ran into a friend from the Wiesel lab and said, ‘Save me.’ ”

That plea led to postdoctoral research in the Rockefeller lab. He stayed as a faculty member until moving to Harvard in 1996.

Mathematics and physics were becoming increasingly important in neurobiology, a trend that has continued, but there was still a certain tension between different mind-sets, he recalled. He found that there were intangible skills involved in biological research. “Good biological intuition was equally important to chops in math and physics,” he said.

“Torsten once said to me, ‘You know, Clay, science is not an intelligence test.’ ”

Though he didn’t recall that specific comment, Dr. Wiesel said recently that it sounded like something he would have said. “I think there are a lot of smart people who never make it in science. Why is it? What is it that is required in addition?”

Intuition is important, he said, “knowing what kind of questions to ask.” And, he said, “the other thing is a passion for getting to the core of the problem.”

Dr. Reid, he said, was not only smart and full of energy, but also “interested in asking questions that I think can get to the core of a problem.”

At Harvard, Dr. Reid worked on the Connectome Project to map the connections between neurons in the mouse brain. The Connectome Project aims at a detailed map, a wiring diagram at a level fantastically more detailed than the work being done to map the human brain with M.R.I. machines. But electron microscopes produce a static picture from tiny slices of preserved brain.

Dr. Reid began working on tying function to mapping. He and one of his graduate students, Davi Bock, now at Janelia Farm, linked studies of active mouse brains to the detailed structural images produced by electron microscopes.

Dr. Bock said he recalled Dr. Reid as having developed exactly the kind of intuition and “good lab hands” that Dr. Wiesel seemed to be encouraging. He and another graduate student were stumped by a technical problem involving a new technique for studying living brains, and Dr. Reid came by.

“Clay got on this bench piled up with components,” Dr. Bock said. “He started plugging and unplugging different power cables. We just stood there watching him, and I was sure he was going to scramble everything.” But he didn’t. Whatever he did worked.

That was part of the fun of working in the lab, Dr. Bock said, “not that he got it right every time.” But his appreciation for Dr. Reid as a leader and mentor went beyond admiration for his “mad scientist lab hands.”

“He has a deep gut level enthusiasm for what’s beautiful and what’s profound in neuroscience, and he’s kind of relentless,” Dr. Bock said.

Showing a Mouse a Picture

That instinct, enthusiasm and relentlessness will be necessary for his current pursuit. To crack the code of the brain, Dr. Reid said, two fundamental problems must be solved.

The first is: “How does the machine work, starting with its building blocks, cell types, going through their physiology and anatomy,” he said. That means knowing all the different types of neurons in the mouse visual cortex and their function — information that science doesn’t have yet.

It also means knowing what code is used to pass on information. When a mouse sees a picture, how is that picture encoded and passed from neuron to neuron? That is called neural computation. 

Nuno da Costa of the Allen Institute prepared a slice of mouse brain for the modified electron microscope at Dr. Reid’s lab in Seattle. “With the brain, you can always go deeper,” Dr. Reid said. Credit Zach Wise for The New York Times

“The other highly related problem is: How does that neural computation create behavior?” he said. How does the mouse brain decide on action based on that input?

He imagined the kind of experiment that would get at these deep questions. A mouse might be trained to participate in an experiment now done with primates in which an animal looks at an image. Later, seeing several different images in sequence, the animal presses a lever when the original one appears. Seeing the image, remembering it, recognizing it and pressing the lever might take as long as two seconds and involve activity in several parts of the brain.

Understanding those two seconds, Dr. Reid said, would mean knowing “literally what photons hit the retina, what information does the retina send to the thalamus and the cortex, what computations do the neurons in the cortex do and how do they do it, how does that level of processing get sent up to a memory center and hold the trace of that picture over one or two seconds.”

Then, when the same picture is seen a second time, “the hard part happens,” he said. “How does the decision get made to say, ‘That’s the one’?”

In pursuit of this level of understanding, Dr. Reid and others are gathering chemical, electrical, genetic and other information about what the structure of that part of the mouse brain is and what activity is going on.

They will develop electron micrographs that show every neuron and every connection in that part of a mouse brain. That is done on dead tissue. Then they will use several techniques to see what goes on in that part of the brain when a living animal reacts to different situations. “We can record the activity of every single cell in a volume of cortex, and capture the connections,” he said.

With chemicals added to the brain, the most advanced light microscopes can capture movies of neurons firing. Electrodes can record the electrical impulses. And mathematical analysis of all that may decipher the code in which information is moved around that part of the brain.

Dr. Reid says solving the first part of the problem — receiving and analyzing sensory information — might be done in 10 years. An engineer’s precise understanding of everything from photons to action could be more on the order of 20 to 30 years away, and not reachable through the work of the Allen Institute alone. But, he wrote in an email, “the large-scale, coordinated efforts at the institute will get us there faster.” He is studying only one part of one animal’s brain, but, he said, the cortex — the part of the mammalian brain where all this calculation goes on — is something of a general purpose computer. So the rules for one process could explain other processes, like hearing. And the rules for decision-making could apply to many more complicated situations in more complicated brains. Perhaps the mouse visual cortex can be a kind of Rosetta stone for the brain’s code.

All research is a gamble, of course, and the Allen Institute’s collaborative approach, while gaining popularity in neuroscience, is not universally popular. Dr. Wiesel said it was “an important approach” that would “provide a lot of useful information.” But, he added, “it won’t necessarily create breakthroughs in our understanding of how the brain works.”

“I think the main advances are going to be made by individual scientists working in small groups,” he said.

Of course, in courting and absorbing researchers like Dr. Reid, the Allen Institute has been moving away from its broad data-gathering approach toward more focused work by individual investigators.

Dr. Bock, his former student, said his experience suggested that Dr. Reid had not only a passion and intensity for research, but a good eye for where science is headed as well.

“That’s what Clay does,” he said. “He is really good in that Wayne Gretzky way of skating to where the puck will be.”

A version of this article appears in print on February 25, 2014, on page D1 of the New York edition with the headline: The Brain’s Inner Language.

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ORIGINAL: NYTimes

By JAMES GORMAN 

FEB. 24, 2014

eLife digital publication

ORIGINAL: http://elife.elifesciences.org/about-the-journal

eLife is a researcher-led, open access digital publication for outstanding research in life science and biomedicine.

The eLife journal is a platform to maximise the reach and influence of new findings and a showcase for new approaches to the presentation, evaluation and use of research.

eLife is a collaboration between the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust, and over 200 of the world’s most talented biomedical scientists.

We aim to make eLife the first choice journal for all researchers, in particular for early-career researchers. It’s important that early experiences of publishing are constructive and fair. eLife is a publishing venue to advance careers in science; the editors act decisively and provide a swift, fair and supportive author experience; and we maximise the potential exposure for all published works.

At eLife, our goal is to accelerate scientific advancement by making new research available quickly, openly, and in a way that helps others to build upon it. We make data more accessible and more useable. We aim to create a broader audience for important discoveries, and to track and report the impact of published articles – on research, and on society as a whole.

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eLife returns decisions on important papers quickly. Our peer-review process is rigorous, but decisive, constructive, and fast.

At eLife, we’ve taken a fresh approach to peer review to save you time, and to provide clear direction and constructive input.

• Decisions are quick and efficient
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Submissions are evaluated by a team of academic editors who are active and respected researchers, who have expertise across disciplines, and who are committed to assessing submissions efficiently and fairly. Our approach focuses on delivering the highest level of service to authors and saving time along the way.

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Our Senior Editors decide whether initial submissions are appropriate for in-depth peer review, usually in consultation with members of the Board of Reviewing Editors. We ask for the research article in a single PDF along with a cover letter. Only once editors commit to full review are authors asked to provide additional information and files to support the peer-review process. We aim to return initial decisions within three to five days. 

Active scientists make all decisions
A Senior editor assigns a member of the Board of Reviewing Editors to oversee the peer-review process. The Reviewing editor usually reviews the article him or herself, calling on one or two additional reviewers as needed.

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Reviewers get together online to discuss their recommendations, communicating openly with one another before a decision is reached, refining their feedback, and striving to provide clear and concise guidance. If the work needs essential revisions before it can be published, the Reviewing editor incorporates those requirements into a single set of instructions. We aim to deliver decisions after peer review within a month of receiving the full submission.

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Obama Seeking to Boost Study of Human Brain

ORIGINAL: NYTimes

By JOHN MARKOFF

Published: February 17, 2013

The Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, seeking to do for the brain what the Human Genome Project did for genetics.

Francis S. Collins, the director of the National Institutes of Health, one of the federal agencies involved in the project. Danny Moloshok/Reuters. 

George M. Church, a molecular biologist at Harvard, said he was helping to plan the project, the Brain Activity Map. Jessica Rinaldi/Reuters.

The project, which the administration has been looking to unveil as early as March, will include federal agencies, private foundations and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

Scientists with the highest hopes for the project also see it as a way to develop the technology essential to understanding diseases like Alzheimer’s and Parkinson’s, as well as to find new therapies for a variety of mental illnesses.

Moreover, the project holds the potential of paving the way for advances in artificial intelligence.

The project, which could ultimately cost billions of dollars, is expected to be part of the president’s budget proposal next month. And, four scientists and representatives of research institutions said they had participated in planning for what is being called the Brain Activity Map project.

The details are not final, and it is not clear how much federal money would be proposed or approved for the project in a time of fiscal constraint or how far the research would be able to get without significant federal financing.

In his State of the Union address, President Obama cited brain research as an example of how the government should “invest in the best ideas.”

“Every dollar we invested to map the human genome returned $140 to our economy — every dollar,” he said. “Today our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs, devising new materials to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation.”

Story C. Landis, the director of the National Institute of Neurological Disorders and Stroke, said that when she heard Mr. Obama’s speech, she thought he was referring to an existing National Institutes of Health project to map the static human brain. “But he wasn’t,” she said. “He was referring to a new project to map the active human brain that the N.I.H. hopes to fund next year.”

Indeed, after the speech, Francis S. Collins, the director of the National Institutes of Health, may have inadvertently confirmed the plan when he wrote in a Twitter message: “Obama mentions the #NIH Brain Activity Map in #SOTU.”

A spokesman for the White House Office of Science and Technology Policy declined to comment about the project.

The initiative, if successful, could provide a lift for the economy. “The Human Genome Project was on the order of about $300 million a year for a decade,” said George M. Church, a Harvard University molecular biologist who helped create that project and said he was helping to plan the Brain Activity Map project. “If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck.”

Scientists involved in the planning said they hoped that federal financing for the project would be more than $300 million a year, which if approved by Congress would amount to at least $3 billion over the 10 years.