Pollard 2009 what makes us human

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Katie Pollard: I've had a long-standing interest in human origins and in anthropology, and I've been curious for a long time in this very broad question of what makes us human. Ever since our species began to walk around on the globe, we've probably been wondering about this. What we're trying to do in my lab is to bring a new type of data, genetic data, and a new tool, which is high-powered computing, to bear on this age-old and fundamental question.

When I was first studying human evolution, most of what we could use were things like bones and artifacts, things that we dug out of the ground, as well as what we observed looking around the Earth today—the behavior of humans and behavior of non-human primates. These were the tools of the trade. I also had an interest in math back then, but I saw very little connection between that and my interest in human origins.

Fortunately, in the next decade, we had a human genome project and then a chimp genome project, and there were major advances in computing. Suddenly this question of what makes us human had a whole new set of data and a whole new set of tools. And I was in a great position to jump into that field. Since chimps are our closest living relative on the tree of life, we can start to figure out what's special about us if we compare our DNA to their DNA.

If we can find the little pieces of our genome that are unique, somewhere hiding in there are messages about what makes humans human. When we finished the chimpanzee genome in and lined it up next to the human genome, we made the amazing discovery that our DNA is almost 99 percent identical. That seems like a bit of a paradox given all the differences we see between ourselves and chimps. But, in fact, it's not a paradox, because all it takes to make a new species, all it takes to make a human, is a few changes in just the right places.

Given that our DNA sequence has about three billion "letters" in it, one percent is still a pretty vast territory to search.

There are about 15 million human-specific letters that have changed in the last six million years, since humans and chimps had a common ancestor. No individual person is going to sit and look through that list.

So tackling this question of which of those 15 million made a difference required writing computer programs. After months of programming and debugging and running my computer code on a massive computer cluster, I finally had some results. The top hit was a sequence that was letters long. And, amazingly, 18 out of those letters were different between human and chimp. To put that in perspective, the same sequence is in the chicken genome and has only two differences between chimp and chicken.

There have been hundreds of millions of years of evolution separating chicken and chimp, and yet we only see two changes. After identifying those regions that were most significantly altered in the human lineage, we will use this functional information to develop testable hypotheses about the effects of the observed changes. Experimental investigations of these genomic regions will lead to new understanding of the evolution of human biology and health. Identification and characterization of the genetic changes leading to modern humans is of fundamental interest.

These investigations also promise to contribute to our understanding of the causal mechanisms behind human diseases, leading to directed treatment and prevention strategies.

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