Charles Darwin and his finches would be proud.
A recent genomics study by Cornell scientists that analyzed the genes of 39 humans and one chimpanzee offers strong evidence that natural selection has shaped human evolution.
In their research, Prof. Carlos Bustamante, biological sciences and computational biology, and his team pinpointed a significant number of genes exhibiting too much variation to be explained by chance. Rather, these genes evolved under the influence of natural selection, the researchers suggest.
Based on the fact that humans and chimpanzees share 99 percent of the same genes and two humans on average share 99.9 percent of the same genes, researchers can establish a degree of variation attributable to random forces in the population.
“If you sequence 50 people, you can quantify how much variation you expect to see [in their DNA sites] – on average I expect to see about two differences between humans and chimps for every difference I see between humans,” Bustamante explained.
Using the two to one ratio as what they called a “yardstick,” the researchers then located all the genes that showed more variability than this baseline ratio predicts.
Compared to the baseline, nine percent of the genes showed too much variation between humans and chimpanzees relative to the variation within humans. The researchers characterized these genes as evidence of positive natural selection, in which favored gene forms are passed down to increase the probability of survival.
Among the positively selected genes were those that coded for immune response, sensory perception, production of sperm and egg, and transcription factors, which turn genes on and off. Many of these gene categories affect a person’s health.
“If you think about the life history of an organism – things that have to do with your health, how likely you are to live past a certain age, genes that allow you to produce twice as much sperm or something will inherently have some positive selection,” Bustamante said.
Another 13 percent of the genes exhibited too much variation within humans compared to between humans and chimpanzees. These genes are slightly deleterious but are not harmful enough for negative natural selection to remove them from the population.
“There is some force that is preventing mutations from becoming fixed between humans and chimps. The idea is that those mutations are bad for you,” Bustamante explained.
Among other things, these genes code for proteins regulating traffic in and out of the cell as well as muscle structure. Many of the negatively selected genes are correlated to hereditary diseases, such as muscular dystrophy and Usher syndrome.
Researcher Scott Williamson grad explained that “even though [the genes] are deleterious, they can reach low frequencies just by chance. The chance they’ll actually spread through the population is really low.”
According to Bustamante, his team has completed much of the legwork for future research into disease.
“There’s 20,000 genes in the human genome,” he said. “You’re trying to associate variation in one of those genes with some disease you’re trying to study. Where do you start?”
One place, he suggested, would be his team’s rankings of human genes by their variations. If scientists looking at these rankings discover the gene they are interested in actually shows no variation across humans, they may think twice about linking the gene to a disease.
Alternatively, scientists can focus on genes that showed negative selection and compare these genes across individuals with a certain disease and individuals without the disease.
The study, published in the Oct. 20 issue of the science journal Nature, is the largest analysis of intra-species and inter-species genetic variation yet. Cornell researchers looked at 11,624 genes, whereas prior studies only examined a few hundred genes.
“The ultimate goal of this work is to try to understand how genetic differences among people contribute to differences in phenotype – why do some people get sick, why are some people overweight,” Bustamante said. “The first step towards tackling any of these questions is to figure out what are the variations among humans.”
He also discussed the research in the context of intelligent design.
“We feel that our study demonstrates there’s clearly been genetic evolution between humans and chimps, and a lot of this presumably has been driven by natural selection,” he said.
Ryan Hernandez grad also worked on the research.
“I have a lot of family members who are religious,” he said. “It’s been a touchy subject every time they ask me what I work on.”
Bustamante plans to conduct similar research into the recently-sequenced genomes of other mammals, such as cows, dogs and pigs.
Other Cornell researchers working on this project included Prof. Andrew Clark, molecular biology and genetics, and Prof. Rasmus Nielson, biological statistics and computation biology.
Celera, a research company that sequenced the genes used in the study, and the National Institutes of Health funded the study.
Archived article by Xiaowei Cathy Tang
Sun Senior Editor