Functional Evolution of Avian RIG-I-Like Receptors

RIG-I-like receptors (retinoic acid-inducible gene-I-like receptors, or RLRs) are family of pattern-recognition receptors for RNA viruses, consisting of three members: retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). To understand the role of RLRs in bird evolution, we performed molecular evolutionary analyses on the coding genes of avian RLRs using filtered predicted coding sequences from 62 bird species. Among the three RLRs, conservation score and dN/dS (ratio of nonsynonymous substitution rate over synonymous substitution rate) analyses indicate that avian MDA5 has the highest conservation level in the helicase domain but a lower level in the caspase recruitment domains (CARDs) region, which differs from mammals; LGP2, as a whole gene, has a lower conservation level than RIG-I or MDA5. We found evidence of positive selection across all bird lineages in RIG-I and MDA5 but only on the stem lineage of Galliformes in LGP2, which could be related to the loss of RIG-I in Galliformes. Analyses also suggest that selection relaxation may have occurred in LGP2 during the middle of bird evolution and the CARDs region of MDA5 contains many positively selected sites, which might explain its conservation level. Spearman’s correlation test indicates that species-to-ancestor dN/dS of RIG-I shows a negative correlation with endogenous retroviral abundance in bird genomes, suggesting the possibility of interaction between immunity and endogenous retroviruses during bird evolution