Research On The Evolution Of Mammalian Virus Receptors

The genetic conflicts between viruses and hosts result in everlasting evolutionary arms race.Viruses require cellular surface receptors,most of which are proteins,to infect host cells.Virus receptors are host proteins that have normal biological functions,but are “hijacked” by viruses to help virus entry.Viral receptors have been subject to two conflicting forces in evolution,namely,negative selection due to functional constraints and positive selection due to host-virus arms race.It remains unclear how virus receptors evolved under multiple selective pressures.In this study,we systematically collated the information of 96 mammalian virus receptors,and studied the evolution pattern of mammalian virus receptor genes in primates using comparative genomics and molecular evolution approaches.We found that 52.1% of virus receptor genes experienced adaptive evolution across the primate phylogeny.Sitemodel analysis showed that 42.7% of virus receptor genes contained positively-selected amino acid sites.Comparing the positively selected amino acid sites and the virus-receptor interaction interface,we found that many of the selected amino acid sites in the virus receptor are located at the virus-receptor interaction interface.Comparison of the virus receptor genes and the control genes of primates revealed that the d N/d S of the virus receptor genes was significantly higher than that of the control genes,the proportion of positively selected genes in the virus receptor genes was significantly higher than the control genes,and the proportion of positively selected branches and positively selected sites in viral receptor genes was significantly higher than that of the control genes.These results indicate that the evolutionary arms race between hosts and viruses leads to the prominent adaptive evolution of virus receptor proteins in primates.We used population genetic methods based on the principles of site frequency spectrum and linkage disequilibrium to analyze the evolutionary pattern of viral receptor genes in human populations.We found that 58 viral receptor genes exhibit natural selection signals in human populations,among which 5 experienced balance selection and 53 experienced selective sweep.In addition,this study found that some viral receptor genes experience different selection pressures in different populations,and the local adaptation of viral receptor genes is consistent with the fact that certain viruses are restricted to specific geographic regions,suggesting that virus is likely to represent an important driving force of human local adaptation.Selective sweep driven by a virus or other factors might lead to the fixation of a resistant allele in a population,which may increase the risk of infection by other viruses or viral strains that has high affinity with the resistant allele,potentially causing epidemics in the human population.Studying the evolution of virus receptor genes has important implications in understanding the evolutionary arms race between viruses and hosts,the host specificity of viruses as well as the emergence of viral infectious diseases.