Neil Shubin’s new book explores the intersection of developmental biology, paleontology and genetics

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Neil Shubin holds part of a fossil from Tiktaalik roseae, a species that fills the gap between fish and land animals. [Credit: Dan Dry]

Your Inner Fish: A Journey into the 3.5-Billion-Year History of the Human Body

By Stuart Fox, SciencelineNYU – Working at the American Museum of Natural History as a teenager, I often heard paleontology derided by scientists in other disciplines. They would call it glorified stamp collecting that lacked experimental rigor. They would question what it contributed to other scientific fields. And most vociferously, they would complain that dinosaurs always made the news while other more useful, if less photogenic, experiments languished without similar fanfare.

For a long time, some of those claims had an air of truth to them. Paleontologists, especially vertebrate paleontologists, didn’t conduct repeatable experiments in the same way physicists or chemists did. And the advances made in vertebrate paleontology didn’t carry over into other fields in the same way chemistry, physics and medicine feed into each other. As for the claim that dinosaurs received undue attention, well, all I can say is people find T-Rexes more interesting than genes. And geneticists better get used to that.

However, in the 1990’s, the chiding became more and more unwarranted. The discovery that a single group of genes regulated body plan and limb development in all animals introduced a genetic angle to the well understood link between development and evolution. That discovery directly connected the evolution studied in paleontology and the human body studied in medicine. After all, many pathologies result from developmental problems in the womb. There, at the intersection of evolution, genetics and development, a new field began to emerge.

Called evolutionary development, or “Evo-Devo” for short, this new field linked human health to evolution by way of the genes that control our progress from worm-like fetus to cute child to jaded, book-reviewing journalist. In short, our eyes, hands, hair, every part of our body is nothing more than the piled-on artifacts of our evolutionary ancestors. Thus, by studying our ancestors, we can gain insight into the way we function. For the first time, paleontology, the field responsible for finding and studying those ancestors, became linked with human health.

Neil Shubin stood at the center of that change. He could be seen as a paleontologist who does genetic experiments or a molecular biologist who also conducts Arctic expeditions in search of fossils. Either way, Shubin embodies the interdisciplinary nature of Evo-Devo.

Shubin discovered a fossil later named Tiktaalik rosae during one of those Arctic expeditions. With a front like an amphibian and a rear like a fish, Tiktaalik became to devotees of Evo-Devo what Archaeopteryx (the part-bird, part-dinosaur fossil) was to the first generation of evolutionary biologists. It was proof of concept, pulled from the rocks at the top of the world.

I met Shubin as a student at the University of Chicago. It was in his class that I first learned about the link between paleontology, genetics and medicine. He was teaching just as much paleontology to the students in his medical school anatomy class as to his paleontology students. Skeptical that paleontology could teach them about medicine, Shubin’s med students needed to be convinced that they couldn’t understand the human body without understanding the evolution of its parts.

That lesson forms the subject of Shubin’s new book, Your Inner Fish. With Tiktaalik as that fish inside us all, and the Evo-Devo paradigm, Shubin explains how our bodies are living zoos, harboring the evolutionary remnants of our many animal ancestors. Throughout the book he details the evolution of different parts of our bodies: how we inherited ears from an ancient fish, our eyes from a jellyfish, and our arms from Tiktaalik. Essentially, we are all missing links, chimeras formed from the lengthy and inexact process of evolution.

The book makes the argument with great élan. Shubin does an excellent job taking the reader on a tour of the natural history of the body by filling the book with colorful facts. For instance, who knew that the evolution of teeth also provided our bodies with the chemical blueprint for making breasts or that the formation of the jaw is linked to the functioning of the inner ear?

But if I was one of Shubin’s medical students, I’m not sure I would be convinced that knowing sharks don’t get hernias would help me practice sports medicine. While the book does an excellent job of reviewing the history behind the human form, the final chapter, where Shubin attempts to link the discoveries of Evo-Devo to familiar ailments, falls a bit flat. He brings up numerous pathologies that result from artifacts left over from our haphazard evolution, such as knee problems and even choking. But he doesn’t say how, if at all, knowing the evolutionary background of the disorders enhances our ability to cure them.

And in a way, that failure is not so much Neil Shubin’s problem as it is the last great problem of Evo-Devo. To fulfill the link Shubin makes between evolution, development and pathology, Evo-Devo needs to point a clear path from fossil to gene to cure. Despite the book’s deft take on a complex subject, I imagine that many people won’t care about their inner fish unless that fish can cure cancer. Of course, those are probably the same people who complain about dinosaurs making more news than proteins. So you probably shouldn’t be listening to them anyways.

Using parasites, viruses and bacteria as tools to confirm the migration of early man and to mark the trail of human evolution

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Microscopic view of T. solium– a pork tapeworm. [CREDIT: STANFORD.EDU]

By Kristin Elise Phillips, SciencelineNYU – Ask most people to describe the bugs that infect our hair, gut and cells, and you’ll get responses like: disgusting, vile, yucky. But ask some scientists to describe them and you’ll get a different response: a window into human evolutionary history.

Lice, tapeworms, viruses, fungi, and bacteria have hitched a ride on the migration, colonization, and social contact that defines the evolutionary history of our species. Tracing changes in parasitic organisms complements what physical anthropologists already know about human evolutionary history from the fossil record and from studying the human genome.

“A goal of science is independent corroboration, and you can’t get more independent than another organism’s genome,” said molecular anthropologist Todd Disotell of New York University.

The organisms that evolved along with humans are quite varied:

Tapeworms were once thought to have first colonized human intestines during the domestication of grazing animals about ten thousand years ago. But a new, careful analysis of the tapeworm family tree using DNA from different species of the parasite has rewritten this story in detail. The association between the host and parasite began two million years ago when tapeworms surreptitiously infested in our small-brained hominin ancestors while they scavenged on carnivore carcasses on the African savannah. We then gave tapeworms to our livestock, not the other way around.

Many theories of human evolutionary history are rooted in the migration of modern peoples from Africa about 60,000 years ago. This migration began from a population of one to ten thousand humans –who are the ancestors of all living people –and led to both the extinction of Neanderthals in Europe and the disappearance of other human species like Homo erectus from other parts of the Old World.

Insight into the African exodus of modern humans comes from comparing the DNA of the only bacteria known to live in the harsh, acidic conditions of the human stomach: Helicobacter pylori. Research by Martin Blaser of New York University’s Medical School and colleagues suggests that Helicobacter pylori first infected our ancestors’ bellies more than 58,000 years ago when humans left Africa, making it an excellent tool for tracing human migration patterns. The global distribution of different strains of stomach bacteria follows the same splits that separated humans into four geographically distinct populations. In fact, stomach bacteria confirm that groups crossing the Bering Straight peopled the Americas since the East Asian strains infect indigenous Amazonians while the European strain is found in South American decedents of colonists.

Several viruses also followed the modern human migration from Africa. In 1993, pathogen research on the human papillomavirus at the National University of Singapore yielded a glimpse into our ancient past. Virologists discovered that this virus, a virus known to cause cervical cancer, splits into three distinct geographical lineages – Caucasian, African and East Asian.

These distinct populations were confirmed in another virus, the ubiquitous human polyomavirus that is associated with harmless kidney infections. This virus similarly splits into Asian/Native American, Caucasian, African and U.S. groupings according to research by Chei Sugimoto, a virologist at the University of Tokyo.

The human polyomavirus has since been used to tease apart genetic relationships among populations of humans from the same geographical region. For example, a group led by Hansjurgen Agostini of the University of Freiburg in Germany confirmed the distinct lineage of the Basque people of the Pyrenees when compared to other Europeans. Agostini and colleagues also found a possible link between the Basques – long thought to be a unique population because of their unusual language – and Spanish gypsies. Other virologists have used polyomavirus to figure out the genetic distinctness of different human populations, the migration pattern among the Pacific Islands, and the number of migrations humans made into the Americas from Asia.

Viruses and bacteria confirm the migration of East Asians into the Americas, but a soil fungus that causes the virulent Valley Fever tells the story of human movement within the Americas. Plant biologist Matthew Fisher of U.C. Berkeley and colleagues found that all Coccidioides immitis infections in South America are of the same strain. The South American strain shares a history with only one of the many North American varieties, suggesting that a subset of people from the north moved south about 10,000 years ago.

Head lice provide insight into an unusual part of the human saga — the time when multiple species of humans simultaneously inhabited parts of the world. David Reed of the University of Florida at Gainesville and colleagues found that head lice have two major lineages. One coincides with the modern human emigration from Africa. The second, however, is more than a million years older. In fact, analysis of louse distribution around the globe proves there was physical contact between modern humans and Homo erectus who had already populated much of the Old World. Homo erectus later went extinct.

The evolution of human pathogens is exciting to physical anthropologists like Disotell. Parasites and viruses not only confirm the human fossil and genomic evidence of our evolutionary history but could potentially answer so much of the unknown. “We may be able to do ancient DNA [tests] on parasites.” Disotell’s eyes pop ever so slightly at the possible avenues of research. “We think syphilis came from New World into the Old World, and we can now test our assumptions. And the plague – did it travel from Asia to the Black Sea to Europe?” Scientists may use ancient parasites to figure out these questions.

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Side-blotched lizards duke it out in a genetic battle of the sexes. [Credit: Erin and Lance Willett]

A lizard family tree offers clues to the balance between reproduction and survival.

By Rachel Mahan, SciencelineNYU – A battle of the sexes is raging in side-blotched lizards, but this is no spectator sport. Until recently, even the scientists who studied them did not have an accurate play-by-play. The conflict happens at the microscopic level of the gene where it is difficult to tell how much it costs to reproduce because some lizards take their genetic secrets to the grave.

“There’s always been this missing piece of the puzzle,” says Andrew McAdam, an evolutionary ecologist at the University of Guelph in Ontario. The lizards that die early and the males, which don’t produce eggs but still carry egg-laying genes from their mothers, have not always been included in estimates of reproductive cost.

McAdam and his colleague Barry Sinervo used a family tree to determine how well lizards survive if they produce different numbers of eggs. When the researchers examined 20 generations of 7000 side-blotched lizards—including males and females that died young—they exposed a lizard tug-of-war. Their results were published recently in the Proceedings of the Royal Society B.

Although the lizards do not actually fight, the battle is over survival. The scientists found that females survive better with the genes for more eggs, while the same genes make males less likely to survive. In other words, “the genes that make you a good female make you a bad male,” says David Reznick, a professor of biology at the University of California, Riverside, who was not associated with the research.

By counting how many eggs female relatives laid, the researchers could approximate how many eggs the males would have laid had they been females. McAdam and Sinervo, the lead author of the study and a professor of ecology and evolutionary biology at the University of California, Santa Cruz, also used the same technique for lizards that died before laying eggs.

Because the researchers knew the parentage of each of the 7000 lizards, “it’s a pretty remarkable study,” says Loeske Kruuk, co-editor of the journal issue, who studies evolutionary biology at the University of Edinburgh in the U.K.

The tiny lizards, which are found in the southwestern U.S. and northern Mexico, are not endangered but offer insight into how evolution works. Common sense would tell scientists that if females produce lots of eggs, they will not be able to waddle fast enough to escape predators. However, the researchers found that more fertile females have a better chance of survival.

“The answer is in the males,” says Sinervo, who is also McAdam’s former mentor. Males fare better if they carry the genes for fewer eggs. The researchers think that hormones associated with increased egg production may hurt males’ survival but help females.

In the grand scheme of things, this battle creates a balance between the sexes and is part of what preserves diversity. If evolution selected the genes for lots of eggs in males and females, scientists might only see lots of eggs.

For other traits, the lizards use a strategy to help ameliorate the tug of war between the sexes. Lizard moms will mate with more than one male and then “sort” the sperm to ensure that all of their babies have the best genes. For example, they give sperm from big males to their sons and sperm from small males to their daughters. Sinervo thinks something like this also could be happening with the genes that determine the number of eggs, although he has yet to investigate.

The study ultimately gives a more complete picture of what is happening in the evolutionary struggles of the side-blotched lizards. Selection, which drives evolution, is “pushing one sex one way, pushing one sex the other way, and the evolutionary equilibrium is in the middle,” says Sinervo.

Even wasps may have the genetic blueprint for motherly love

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Wasps’ behavior is strongly influenced by the maternal care they receive, according to a new study. [Credit: Eric Wheeler]

By Greg Soltis, SciencelineNYU – Tell your mom that she has the maternal instinct of a wasp. It’s a compliment. Really, it is. New research shows that some of these insects have motherly love in their genes.

Previous behavioral observations of wasps led scientists to consider that maternal behavior can serve as a stepping stone along the transition from solitary to social behavior. In the first experiment to confirm these observations, scientists at the University of Illinois at Urbana-Champaign used a new sequencing method to show a genetic link between the maternal behavior of Polistes metricus paper wasps and the nurturing and provisioning behavior of the worker wasps.

“Based on gene expression results, brains of altruistic individuals look like maternal individuals,” says Amy Toth, a postdoctoral researcher and lead author of the study, which appeared in the journal Science.

Although the queen is the genetic mother of the workers, researchers showed that the gene expression of the givers and recipients of maternal care was more similar than those of the mother and offspring. The behavior-related genes provided the molecular basis of this altruistic behavior in wasps. Researchers also found different behavioral gene expressions in the brain of the wasp during the maternal and reproductive stages.

Wasps’ behavior changes over the course of their lives, unlike the behavior of ants and honey bees. Foundresses, who often lead a solitary life before becoming caretakers, assume a maternal role. They establish new colonies and, like a nanny, care for their adopted larvae on their own. When these larvae mature into workers, they mimic this behavior and go on to forage for food and care for their siblings. Successful foundresses become queens after rearing this generation of workers and no longer provide for the younger wasps. But other foundresses ultimately sacrifice their opportunity to reproduce.

The maternal phase seems to provide a connection between less and more evolutionarily advanced stages in the life of a wasp. “This is why it is interesting to study the maternal transitional state between solitary and honey bee-like behavior,” Toth notes.

Nature provides other examples of individuals like foundresses who care for newborns outside their genetic family, such as younger wolves who eat their prey and later regurgitate for hungry pups. These roles often permit higher growth rates and larger families in the animal community, says Sarah Hardy, an anthropologist at the University of California, Davis.

Genes that help a species survive and reproduce, like those that foster maternal behavior, are more likely to be inherited by the next generation. “The evolution of altruism across species is linked to the preservation of offspring, and the most hard-core manifestation of this is the occurrence of maternal altruism,” says Stephen Post, president of the Institute for Research on Unlimited Love at Case Western Reserve University in Cleveland. Human parents strongly invest in their offspring since they have a limited number of eggs at their disposal, according to Post, who is also a professor of biology, philosophy and theology. He says this underlies the importance of parental tenderness and cherishing.

Like Post, Toth recognizes the uniqueness of humans. But she points out that a lot of criteria for human behavior are found in animal studies. “Animals and insects are more complex than you think,” Toth says.

Because of the sequencing method used in collaboration with the company 454 Life Sciences, which pioneered this technique, these researchers were not restricted to model species such as rats or flies. The new application allowed them to test an evolutionary hypothesis on a species without a genome sequence, which saved researchers both time and money. Instead of analyzing the entire genome, they focused on genes that could be detected in wasp brains and sequenced using this new approach.

Since little data was previously available for paper wasps, bioinformaticians from the Illinois crop sciences department compared the sequenced wasp DNA fragments to parts of the fully sequenced honey bee genome. They found 32 wasp genes, also known to be related to honey bee behavior, and used these genes as the basis for the study.

Wasps and honey bees had a common ancestor between 100 million and 150 million years ago. While their DNA sequences have changed significantly, proteins encoded by these genes that relate to behavior have not. This allowed researchers to confidently identify relevant genes and compare the two species.

Current attempts are under way to broaden the scope of this study, according to Toth. She recognizes that 32 genes are “a lot better than one but certainly not the whole picture.”

Because genes do not act in isolation, these researchers have developed the technology to study 5,000 genes at once. Toth hopes to apply these new methods and technologies to learn more about which genes affect aggressive behavior.

But the significance of this study cannot be overlooked. Rather than using rats, flies or other model species, Toth acknowledges that she and her co-workers successfully studied a species without a genome sequence and “used a sequencing method to get a ton of information about wasp species and test an interesting hypothesis about evolution.”