Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals

Abstract

Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-α, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens.

Tissue-specific genes as an underutilized resource in drug discovery

“…Fractional values of K a /K s are indicative of negative selection pressure favoring between-species conservation of an amino acid sequence. By contrast, K a /K s values exceeding 1 may in some cases indicate that positive selection pressure has favored evolutionary divergence of orthologs, as exemplified by immune genes adapted to species-specific pathogens 23–26 .…”

Hemoglobin E protects against acute Plasmodium vivax infections in a Kachin population at the China–Myanmar border

“…Malaria is the strongest known evolutionary force of selection in the recent history of human genome (35). Analysis of various hemoglobinopathies indicates that hemoglobin mutations confer protection against malaria, but differ in the degree of protection against uncomplicated malaria and asymptomatic infections (4, 5, 36).…”