Theme of the year: be a gap junction

I think it's a good idea to set out with a purpose for the new year. If there is one thing that describes the important work underway, it is bridging the gap between the natural history of humans and our molecular makeup.

Except, well, "bridging the gap" is way too overused. It's like "building bridges to the 21st century" and the like. Plus, it has this huge structural connotation. It takes a lot of people working together to build a bridge. Everybody knows that.

That's why it's such a good metaphor: plausible deniability. "Hey, the bridge didn't get built? What are you looking at me for? I'm supposed to build a bridge all by myself? Get outta here!"

So I'm picking "be a gap junction". Let's look at what they are:

A gap junction is a junction between certain animal cell-types that allows different molecules and ions to pass freely between cells. The junction connects the cytoplasm of cells.

It makes a certain kind of connection between two things, allowing things to flow between them -- like a bridge. But it's tiny and operates rapidly, on a molecular scale. It's an individual, although it may work collectively with others.

For me, the gap junction is a perfect embodiment of this year's theme -- making connections between human molecular evolution and human natural history.

The evolution of our molecules has been coming rapidly into focus. Much more information about the broad scale of human molecular evolution will be coming online this year. There aren't so many people who can take this information and find the aspects of human natural history that it can address. The important changes in human evolution -- beyond the brain to other aspects of our biology, such as life history, diet, and social strategies -- are just as much a black box to many molecular biologists as genomics has become to many traditional anthropologists. There is something interesting there, no doubt, but what is it?

That's my field. That's what I'm working on. It's really exciting.

I bring this up not only because of the New Year, but also because of this article by Carl Zimmer in the current PLoS Computational Biology. It may not be a journal you typically read, but it's open access and worth a look.

Zimmer sets out to describe the dichotomy between natural historians -- paleontologists, field biologists, ecologists, and the like -- and molecular biologists. He gives a quick account of the hippo-whale problem, but it is in no sense exceptional -- anthropology has it's own examples of phylogenetic discord between molecular and paleontological specialists, such as Ramapithecus. The point is that there are increasingly two kinds of data -- molecular and natural historical -- and nobody is a specialist in both:

This experience made a strong impression on me. I was struck by the divide between these two kinds of biologists. Each group had a profound confidence in their own sources of information, and an abiding skepticism about the other's. As I learned more about the history of modern biology, I realized that this rift did not begin in the 1990s. It was already present in the 1950s, as molecular biologists began championing their new science over more traditional ways of understanding life.
Harvard University's biology department was a microcosm of this conflict. James Watson, fresh from discovering the structure of DNA, breezed into the department in 1956 with revolution on his mind. It was time to sweep beyond mere description of animals and plants and move into a new biology based on chemistry and physics, as Watson's biographer, Victor McElheny, writes [4].
Needless to say, the Harvard naturalists were not happy. Edward O. Wilson, entomologist, ecologist, and sociobiologist, pushed back hard. Watson, having risen to historic fame at an early age, became the Caligula of biology, he writes in his autobiography, Naturalist. It was foolish, we argued, to ignore principles and methodologies distinctive to the organism, population, and ecosystem, while waiting for a still formless and unproved molecular future [5]. The struggle only ended when Harvard's biologists agreed to split their department in two.

The Watson-Wilson dichotomy is an emblematic example, in that the real problem is as more due to personality and temperament than to the inherent difficulty of the subject. How many molecular biologists are requiring their students to learn about the fossil record? How many natural historians have been requiring molecular biology and genetics of their students? The answer is not zero -- indeed, far from it. But one or two courses in genetics generally give a good grounding in the molecular biology of ten years prior. The fossil record doesn't change so quickly, but a full theoretical grounding in the means of analyzing fossil samples takes a long time. It is very easy to pick and choose hypotheses and worry about the niggling doubts later.

As Zimmer points out, this problem of training leads to absurd extremes. Imagine a paper summarizing the evolution of a mammalian family -- one richly represented in the fossil record -- that doesn't include a single fossil.

One example of this new ambition was a paper published earlier this year on the evolution of cats [6]. The scientists offered a sweeping scenario for cat evolution, complete with migrations of cats out of Asia into the New World and back, along with the emergence of the major groups of felids, ranging from ocelots to bobcats to lions. The scientists based their scenario entirely on an analysis of cat DNA. They did not consider a single fossil of a cat, nor did they have a paleontologist expert on cats as a coauthor. Cat fossil experts inform me that fossils of true cats as old as 17 million years have been discovered in North America. The geneticists put the arrival of cats in North America at only 8 million years ago. Whether or not the DNA results are correct, it is striking that the report does not even mention the existence of fossils that do not fit the pattern.

Zimmer has written much about natural history, and has great sympathy for the paleontologists he has worked with. So the article's theme is the value of natural history knowledge as applied to molecular information (he refers to this as "computational biology", but that gives the lab guys short shrift). As an example, he describes the evolution of early vertebrates: Molecular information shows evidence for genome duplication between present-day jawed vertebrates and the agnathans. As Zimmer points out, this led the hypothesis of a sudden burst of evolution leading to the features of jawed vertebrates, but paleontology shows that the jawed vertebrates emerged gradually in the fossil record over a long time, with different features emerging at different times. In this instance, a "striking" hypothesis from considering molecular features in isolation is easily disproved by looking that the fossil record.

This is the frontier of human evolution: integrating the data from human genomics with our knowledge of human prehistory. The days when we had to argue about the phylogeny of a single gene are long behind us. Anthropological genomics is about being a "gap junction" -- taking specialist knowledge of human prehistory and applying molecular information to test evolutionary hypotheses.

And if single genes are behind us, so are single events. "Out of Africa" doesn't explain everything, nor does the origin of Homo, the origin of the hominids, or any other single event. When we were limited to one gene, we were limited to one event, more or less. More than likely, that one event really was about natural selection and the phenotypic expression (or linkage) of the gene. Genomics has opened new doors that let us examine the evolution of phenotypes over hundreds of thousands of years. We can examine the differences between loci in their genealogical patterns, and in some cases we can link those differences to demographic events.

It's about finding diversity among the evolutionary histories of different genes, and linking that diversity to the diverse causes of our own evolution. This will be the year that a true anthropological genomics begins to emerge.

References:

Zimmer C (2006) The Genome: An Outsider's View. PLoS Comput Biol 2(12): e156 DOI: 10.1371/journal.pcbi.0020156