Frequent segmental sequence exchanges and rapid gene duplication characterize the MHC class I genes in lemurs

Abstract

Major histocompatibility complex (MHC) class I genes have complicated and profound evolutionary histories. To reconstruct and better understand their histories, partial class I genes (exon 2-intron 2-exon 3) were sequenced in a sampling of prosimians (Strepsirhini, Primates). In total, we detected 117 different sequences from 36 Malagasy prosimians (lemurs) and 1 non-Malagasy prosimian (galago) representing 4 families, 7 genera, and 13 species. Unlike the MHC class II genes ( MHC-DRB), MHC class I genes show a generally genus-specific mode of evolution in lemurs. Additionally, no prosimian class I loci were found to be orthologous to HLA genes, even at highly conserved loci (such as HLA-E, HLA-F). Phylogenetic analysis indicates that nucleotide diversity among loci was very small and the persistence time of the polymorphisms was short, suggesting that the origin of the lemur MHC class I genes detected in this study was relatively recent. The evolutionary mode of these genes is similar to that of classic HLA genes, HLA-A, HLA-B, and HLA-C, in terms of their recent origin and rarity of pseudogenes, and differs from them with respect to the degree of gene duplications. From the viewpoint of MHC genes evolution, some interlocus sequence exchanges were apparently observed in the lemur lineage upon phylogenetic and amino acid motif analyses. This is also in contrast to the evolutionary mode of HLA genes, where intralocus exchanges have certainly occurred but few interlocus exchanges have taken place. Consequently, the gene conversion model for explaining the generation of the MHC diversity among different loci can be thought to play more important roles in the evolution of lemur MHC class I genes than in that of HLA genes.

Preservation of a Pseudogene by Gene Conversion and Diversifying Selection

“…The observed number of such shared polymorphic sites is far beyond that explained by multiple mutations. There are a number of shared polymorphic sites among other HLA-DRB genes (not shown), indicating that gene conversion has been active in the HLA-DRB cluster, thereby contributing to the introduction of new types of PBR.Very similar patterns are also observed in other primates (Go et al 2003;Abbott et al 2006;Doxiadis et al 2006). Of particular interest is chimpanzee's ortholog of HLA-DRB6 (represented by Patr-DRB6), which has a very high level of variation, although it is a pseudogene.…”

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

“…There was no evidence that either locus was a pseudogene; thus, all loci are assumed to be functional. Gene duplications are common in the MHC (Kasahara, 1999;Go et al, 2003;Kelley et al, 2005) and coexpression of duplicated loci might be selectively favoured due to increased parasite recognition (Nuismer and Otto, 2004). Duplication events seem to be a common feature in lemurs (Go et al, 2003).…”

Patterns of variability at the major histocompatibility class II alpha locus in Atlantic salmon contrast with those at the class I locus

“…Different modes of binding the peptide by class I and class II molecules, relatively strict in class I and more permissive in class II, may be responsible for functional differences between the two classes of MHC molecule, e.g differences in positive and negative selection of T cells (Huseby et al 2003). The different nature of peptide binding may be one reason for the different evolutionary rates between class I and class II genes, as has been proposed to explain the higher turnover of the class I genes with respect to the class II genes in primates (Go et al 2003). Under this model, stricter peptide binding by class I molecules would promote a higher rate of change in order to adapt to new infections (Go et al 2003).…”

“…The different nature of peptide binding may be one reason for the different evolutionary rates between class I and class II genes, as has been proposed to explain the higher turnover of the class I genes with respect to the class II genes in primates (Go et al 2003). Under this model, stricter peptide binding by class I molecules would promote a higher rate of change in order to adapt to new infections (Go et al 2003). However, the nature of class I peptide binding specificities has not been determined in fish and our present results for Atlantic salmon contrast with the situation in the Lake Tana barbs species flock where closely related species have been shown to share class I alleles but differ in their class II alleles.…”