April Flowers for redOrbit.com – Your Universe Online
A new genome-wide analysis, led by the University of Chicago Medical Center, searched for evidence of long-lived balancing selection – where the evolutionary process acts not to select the single best adaptation but to maintain genetic variation in a population. The study revealed at least six regions of the genome where humans and chimpanzees share the same combination of genetic variants.
The results of this study have been published in a recent issue of Science.
The findings suggest that human variation in these regions dates back to a common ancestor with chimpanzees, millions of years ago before the species split apart. The importance of the dynamic co-evolution of human hosts and their pathogens in maintaining genetic variation is also highlighted by this study.
Keeping all hereditary options open is the function of balancing selection. A classic example of balancing selection in humans is the presence of two versions of the hemoglobin gene: a normal version and hemoglobin S.
Hemoglobin S is a mutation that distorts the shape and function of red blood cells. If a person inherits two normal hemoglobin genes, they are at high risk for malaria; a parasitic disease that infects more than 200 million people each year. A person who inherits one normal and one hemoglobin S gene is partially protected from malaria, which is a potentially life-saving benefit. A person with two copies of hemoglobin S suffers from sickle-cell anemia — a serious and life-long circulatory disease.
“When we looked for genetic clues pointing to other, more ancient, examples of balancing selection, we found strong evidence for at least six such regions and weaker evidence for another 119–many more than we expected,” said Molly Przeworski, PhD, professor of human genetics and of ecology and evolution at the University of Chicago.
“We don’t yet know what their functions are,” she said.
None of the six regions codes for a protein. There are clues that they are involved in host-pathogen interactions, “but which pathogens, what immune processes,” she said, “We don’t know.”
The team, which included members from Oxford University, the Biomedical Primate Research Centre in the Netherlands and the University of California at San Francisco (UCSF), used data on 10 West African chimpanzees and 50 sub-Saharan humans who were part of the 1,000 Genomes Project.
The scientists examined the data, looking for cases in which genetic variations that arose in the ancestor of both species have been maintained through both genetic lines. That variation in these genomic regions has persisted for so long the that they “must have been functionally important over evolutionary time,” Ellen Leffler, a graduate student in Przeworski’s laboratory, said in a statement.
The study was designed to be very conservative. “We wanted to find the cases we believed the most, rather than the most cases,” Przeworski added.
Snippets of data from humans and chimps were sorted by computer into clusters, depending on how similar the subjects were to each other. As expected, for most snippets they found a cluster of humans and a separate cluster of chimps. There were a few segments, however, in which each cluster included both chimpanzees and humans. In those regions, some humans were more closely related to chimps than to other humans.
“Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare,” the authors wrote. The oldest, and probably best-known, example of balance polymorphism shared between humans and chimpanzees is the major histocompatibility complex (MHC). MHC is a group of genes that help the immune system distinguish between the body and potential invaders like bacteria and viruses.
In a previous study last year, Przeworski and her team found that humans and gibbons shared genetic variation related to the ABO blood-group system from a common ancestor.
The six regions found in this current study appear to play a role, like the MHC, in fending off infectious disease, which requires a variety of evolutionary tools, including balancing selection. If, for example, a population moves to a new environment – such as the exodus out of Africa to northern Europe — there are many onetime adjustments that must be made, such as adjusting to less intense sunlight and decreased ultraviolet radiation. A decrease in melatonin production over many generations is a static adaptation for a static environment.
Fighting off pathogens, on the other hand, is more dynamic like a constant arms race. Chimps and humans alike may have been able to retain multiple lines of defense that can be called on when a pathogen evolves new weapons through balancing selection.
“Our results imply that dynamic co-evolution of human hosts and their pathogens has played an important role in shaping human variation,” Przeworski said. “This highlights the importance of a different kind of selection pressure in human evolution.”