Balancing selection is a mode of adaptation that conserves regions of genetic diversity within a genome even when the population or species being examined is subject to genetic drift. Genetic diversity in a population is often described as an increased number of heterozygotes. On a more molecular level, however, balancing selection and therefore increased genetic diversity is suggested when a certain number of single nucleotide polymorphisms (SNPs) or haplotypes in a population are seen more often in a region of interest than would be expected by genetic drift or mutation alone.
Evidence has suggested that balancing selection most often occurs when the region of genetic diversity increases organismal fitness evolutionarily. A common example of balancing selection in humans is sickle cell anemia. With this heterozygote advantage individuals with one normal and one sickle cell allele have a greater ability to resist malaria. Multiple studies have shown that balancing selection most often arises from predator-prey or host-pathogen interactions. Selected, closely-linked sites can be indicative of ancient balancing selection if the genetic variation in the population is accumulated over long periods of time.
Due to recent genome sequencing technology and genome wide analysis researchers have the chance to search and compare human and chimpanzee genomes for ancient balancing selection. A recent paper by Leffler et al. published in March of 2013 titled, Multiple instances of ancient balancing selection shared between humans and chimpanzees, highlights regions of the human and chimpanzee genomes that suggest potential balancing selection that would have occurred in an ancient common ancestor before the human-chimpanzee split. In order to find areas indicative of balancing selection genome wide scans were used to search for regions of high diversity that would not likely be seen under genetic drift, mutation, or other selective pressures. While conducting this study researchers looked for ancestral polymorphisms present in both the humans and chimpanzees that are identical by descent (IBD) in order to eliminate the probability that such polymorphisms in selected regions would be due to chance alone.
When identifying shared SNPs between the two species, the complete genome sequences from 59 humans from sub-Saharan Africa and 10 Western chimpanzees were examined. From the data that was produced, the researchers found that the shared SNPs include a much higher proportion of CpGs (regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along a region of DNA). This observation suggests that “most instances of shared SNPs are due to the independent occurrence of the same mutation in both species”. This indicates that the SNP similarities are identical by state rather than descent between the human and chimpanzee populations that were examined. So, one may think that balancing selection does not play a significant role in the identification of shared SNPs….
Along with identifying shared SNPs, protein variants were also analyzed in order to determine the prevalence of balancing selection. The MHC stood out in the analysis. This observation in the commonality of the MHC protein variant includes six nonsynonymous and three synonymous SNPs that were not among the many cases of shared haplotypes in this region indicating a relationship between the two species’ genomes.
The most notable shared SNP found between the human and chimpanzee genome is a nonsynonymous SNP in GP1BA. This gene encodes a glycoprotein present on the membrane of platelets that is responsible for binding to the ABO antigens expressed on the Von Willebrand Factor. The specific polymorphism in this gene shared between chimps and humans affects the actual binding to the Von Willebrand Factor and is associated with platelet count. These results from the protein variant analysis leads researchers to believe that the two genes in the two species may have been targets of long-lived balancing selection.
125 regions outside the MHC with shared haplotypes were identified between chimpanzees and humans. In five of the regions that were located with shared haplotypes, there are more than two pairs of shared SNPs in significant linkage disequilibrium. This indicates that balancing selection could play a role in the incidences of shared haplotypes between the two species.
The phylogenetic tree generated based on the regions of shared haplotypes, shows that haplotypes from different species that carry the same allele are more closely related to each other than to haplotypes from the same species with the other allele. This pattern of clusters represented by the tree indicates that these cases of commonality cannot be explained solely by recurrent mutation. This investigation is another piece of evidence in support of the presence of balancing selection.
What do you think? Is there enough evidence to suggest balancing selection within the human and chimpanzee genomes? Where could researchers go from here? What should they look at next?