MHC molecular evolution in chimpanzees

By: Sarah Boles, Carly Russell, Tia Zephir, and Gabby Scarcella (Stonehill College, BIO323: Evolution, Spring 2021)

Have you ever wondered how your immune system just knows and acts on a variety of diseases? Especially now during COVID-19, it seems our immune systems are really being put to the test. The actions of your immune system are due to the major histocompatibility complex (MHC). In  a recent article in BMC Evolutionary Biology, researchers from the University of Geneva and the Biomedical Primate Research Center wanted to see if MHC genes are conserved and evolving similarly in Western chimpanzees (Pan troglodytes verus) and humans. The MHC region, referred to as Patr in chimpanzees and HLA in humans, is a family of genes that plays a key role in a population’s adaptive immunity. MHC diversity could affect a population’s survival because these genes code for proteins that help combat viral infections and protect the organism from harmful pathogens. MHC genes are classified as class I genes or class II genes, which differ in structure and function. The class I genes are named A, B, and C, and target viral invaders, whereas class II genes, such as DPB1, DQB1, DQA1, and DRB1, target parasitic and bacterial invaders. The objective of this study was to determine if the genetic diversity at different Patr genes is significantly reduced in present day Western chimpanzees due to a past bottleneck effect, which is defined as the sudden decrease of a population from natural causes. The researchers also compared human and chimpanzee genetic diversity to determine if MHC molecular evolution mechanisms were conserved between the two species.

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Allelic richness, heterozygosity, and nucleotide diversity were measured in this study. Allelic richness refers to the number of alleles an individual has, and heterozygosity is the tendency of an individual to have two different alleles at a gene. From these, it was discovered that there was a very similar pattern of diversity across seven MHC loci, which are fixed places on a chromosome, between humans and chimpanzees. Overall, allelic richness and heterozygosity are greater at the MHC loci A, B, C (class I), and DRB1 (class II), compared to DQA1, DQB1, and DPB1 (class II). Also, nucleotide diversity is greater at the DRB1, DQA1, DQB1 (class II), and locus B (class I) compared to A, C (class I), and DPB1 (class II). There were also similar patterns of linkage disequilibrium across Patr and HLA genes. Linkage disequilibrium is the non-random association of alleles at different genes in a population. These results indicate that conservation of MHC diversity patterns in humans and chimpanzees was driven by similar evolutionary mechanisms. Nucleotide diversity was similar in both species. It is primarily created via point mutations at the class II loci, DQB1 and DQA1, and the class I loci, C and A. It’s also created through recombination and/or gene conversion at the class II loci DRB1 class I locus A, when chromosomes mix their genetic information to create new alleles.

Demographics and natural selection also play a role in affecting the MHC genes in both species. The three genetic diversity indexes that were looked at were similar between Western chimpanzees and humans that underwent rapid genetic drift, but lower than larger populations of humans. Genetic drift is a change in allele frequency due to random chance. This reduced diversity in chimpanzees’ MHC loci was due to strong selective sweep, which is when an allele basically takes over a population, as caused by a viral pathogen followed by bottlenecking. As a result, many Patr class I alleles would have been lost, and the only surviving chimpanzees would be those with alleles with resistance to the pathogen. At least two modes of natural selection provide evidence that humans and chimpanzees share ancient MHC lineages at loci DQB1, DQA1, DRB1, C, and A. For class II genes, there would have been less of an effect in terms of a response to a viral pathogen because they respond more to parasitic and bacterial infections. The chimpanzee class II genes (Patr-DB1) underwent a selective sweep due to a low allelic richness compared to the chimpanzee class I gene, Patr-B. Also, since Patr-DRB1 evolves through recombination and/or gene conversion, it would have lost its diversity. Patr-DQA1 and Patr-DQB1 have different levels of nucleotide diversity and heterozygosity, with DQA1 being high and DQB1 being low. Patr-DQB1 is the most divergent loci for both nucleotide diversity and heterozygosity, which evolves under selection. High levels of heterozygosity can be explained by balancing selection, which is when the alleles are maintained even though genetic drift occurred, along with point mutations.

This study supported the idea that the MHC genes were influenced by similar evolutionary mechanisms in humans and chimpanzees, leading the researchers to believe that these genes are highly conserved in both species. Usually with bottleneck effects, there is low genetic diversity, especially with low population sizes. However, it was found that there was not a significantly low level of genetic diversity in the Western chimpanzees Patr genes compared to the HLA genes of humans who underwent rapid genetic drift. This means that since there was no significant difference, something must have happened in the chimpanzees that increased the genetic diversity of their MHC region. This recovery is most likely due to balancing selection and recombination. The ability to regain high genetic diversity of these MHC regions is essential for immunity from different diseases for chimpanzees, as well as other species. Being able to regain high genetic diversity is what could have allowed the MHC genes to be conserved throughout the species.

Article: Vangenot, C., J.M. Nunes, G.M. Doxiadis, E.S. Poloni, R.E. Bontrop, N.G. de Groot, and A. Sanchez-Mazas. 2020. Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution. BMC Evolutionary Biology 20: 119. https://doi.org/10.1186/s12862-020-01669-6