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.

Immunoglobulins are important elements of the adaptive immune system that bind to an immense variety of microbial antigens to neutralize infectivity and specify effector functions. In the present study, the immunoglobulin heavy chain constant region (IGHC) genes from marine mammals were identified and compared with those of their terrestrial relatives to explore their genomic organization and evolutionary characteristics. The genomic organization of marine mammal IGHC genes was shown to be conservative with other eutherian mammals. Stronger signals of positive selection on IGHC were revealed in terrestrial mammals than that in marine mammals with the branch-site model, displaying different selective pressure, which might suggest their divergent adaptations to contrasted environments.

Background Cetacean hindlimbs were lost and their forelimb changed into flippers characterized by webbed digits and hyperphalangy, thus allowing them to adapt to a completely aquatic environment. However, the underlying molecular mechanism behind cetacean limb development remains poorly understood. Results In the present study, we explored the evolution of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with that of other mammals. TBX5, a forelimb specific expression gene, was identified to have been under accelerated evolution in the ancestral branches of cetaceans. In addition, 32 cetacean-specific changes were examined in the SHH signaling network (SHH, PTCH1, TBX5, BMPs and SMO), within which mutations could yield webbed digits or an additional phalange. These findings thus suggest that the SHH signaling network regulates cetacean flipper formation. By contrast, the regulatory activity of the SHH gene enhancer—ZRS in cetaceans—was significantly lower than in mice, which is consistent with the cessation of SHH gene expression in the hindlimb bud during cetacean embryonic development. It was suggested that the decreased SHH activity regulated by enhancer ZRS might be one of the reasons for hindlimb degeneration in cetaceans. Interestingly, a parallel / convergent site (D42G) and a rapidly evolving CNE were identified in marine mammals in FGF10 and GREM1, respectively, and shown to be essential to restrict limb bud size; this is molecular evidence explaining the convergence of flipper-forelimb and shortening or degeneration of hindlimbs in marine mammals. Conclusions We did evolutionary analyses of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with those of other mammals to provide novel insights into the molecular basis of flipper forelimb and hindlimb loss in cetaceans.