Volume 5, Issue 38 July/August 2008
Tracing Evolution in Genes
Evolutionary biologist Rasmus Nielsen uses in silico experiments to identify traces of rapid evolution in genes. Photo credit: courtesy Rasmus Nielsen
How do humans differ from chimpanzees? The average Homo sapiens has no trouble counting the ways. Just for starters, we're taller, less hairy, and-a point no one fails to mention-far brainier than our closest primate relatives.
All of these differences and more have emerged over the past five million years, when the common ancestor of both species reached an evolutionary fork in the road. How early hominids came to walk the savannah, while early chimpanzees returned to the forests, has fascinated professional scientists and armchair anthropologists alike.
The best way to answer those questions, according to Rasmus Nielsen, is to study our respective genomes. "Evolutionary biology is an historical science," says Nielsen, a Berkeley professor of integrative biology. "But in the absence of a time machine, we can't really go back and show exactly why certain evolutionary events occurred. All we have to work with is what we observe today. So we look at the DNA to see the evidence for past Darwinian selection."
Nielsen uses the power of statistics and computing to compare the DNA of different species or populations. By identifying which sets of genes have changed, or mutated, he can describe how ancestral populations diverged step by tiny genetic step. His work not only recasts the story of human evolution but promises to uncover the genetic roots of many diseases.
Nielsen's approach sorts genetic mutations into two general categories. The first involves changes that have little or no effect on the fitness of an organism. Mutations in these sequences tend to accumulate at a relatively slow background rate, so they tend not to be dramatically different between organisms. Other mutations do have a direct impact on an organism's survival, because they alter the structure or function of a gene or its protein. Exposed to the pressures of the real world, these traits tend to get amplified or weeded out at a much faster rate. In a practical sense, the genes with the most dramatic differences are also those that have undergone intensive evolutionary selection.
Nielsen uses statistics and computational biology methods to identify the hallmarks of rapid evolution in genes. His techniques are revealing which traits played starring roles in the evolution of humans and chimpanzees. Photo credit: Aaron Logan, Wikipedia
With this approach, Nielsen is revising the story of what drove humans and chimpanzees apart. "Biology has had a lot of just-so stories about why something might have been adaptive," he says. "Having the genomic data from many species gives us the opportunity to test some of these hypotheses."
In a recent study, Nielsen compared more than 13,000 genes common to both chimpanzees and people. The types of genes that differed the most, he found, had to do with the immune system, sensory perception, long-bone growth, and cancer control. By contrast, the genes that affect humanity's most prized possession-the brain-had changed very little.
"It was a big surprise," Nielsen says. "We would expect brain development to be one of the big areas of differences between humans and chimpanzees." This suggests that relatively few genetic changes may be responsible for the differences in the brain between humans and chimpanzees.
Nielsen is now using this approach to flag genetic mutations associated with hereditary diseases. On average, individuals with disease-causing mutations will leave behind fewer offspring. These disease-causing mutations are under especially intense Darwinian selection pressure. "By looking at which genes are under selection, we can actually flag which particular mutations are more likely to cause diseases." Nielsen says.
Conditions such as cardiovascular disease and autism have resisted useful genetic analysis because they are likely caused by multiple, interacting genetic components. Nielsen's techniques, which make statistical associations between multiple genes, are ideal for the job. Once a suite of genes is linked with a disease, scientists can make far more rapid progress developing cures that could someday benefit human and chimpanzee alike.