Divergent Selection of Pattern Recognition Receptors in Mammals with Different Ecological Characteristics

Ran Tian, Meixiu Chen, Simin Chai, Xinghua Rong, Bingyao Chen, Wenhua Ren, Shixia Xu, Guang Yang

Pattern recognition receptors (PRRs) are specialized receptors that represent a key component of the host innate immune system. Whether molecular evolutionary history of different PRR classes have involved different genetic mechanisms underlying diverse pathogen environment in mammals, and whether distinct ecology of mammals may have imposed divergent selective pressures on the evolution of the PRRs, remained unknown. To test these hypotheses, we investigated the characterization of 20 genes belonging to four PRR classes in mammals. Evidence of positive selection was found in most (17 of 20) PRR genes examined, and most positively selected sites (84%) undergoing radical changes were found to fall in important functional regions, consistent with the co-evolutionary dynamics between the hosts and their microbial counterparts. We found different evolutionary patterns in different PRR classes, with the highest level of positive selection in C-type lectin receptor (CLR) family, suggesting that the capability of CLRs in response to a wide variety of ligands might explain their malleability to selection pressures. Tests using branch models that partitioned the data along habitat and social behavior found significant evidence of divergent selective pressures of PRRs among mammalian groups. Interestingly, species-specific evolution was detected on RIG-I-like helicase genes (RLRs) in cetaceans, suggesting that RLRs might play a critical role in the defense against widespread marine RNA viruses during their divergence and radiation into marine habitats. This study provides a comprehensive look at the evolutionary patterns and implications of mammalian PRRs, and highlights the importance of ecological influences in molecular adaptation.