Abstract
BackgroundWhether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.ResultsBy comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the α3 domain, but our results suggest that homogenisation also concerns certain residues of the α1–α2 codomain that lie outside the antigen recognition site.ConclusionA model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation.ReviewersThis article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti.
Highlights
Whether major histocompatibility complex (MHC) molecules undergo concerted evolution or not has been the subject of a longstanding debate
A major histocompatibility complex (MHC) is found in the genome of all vertebrates from cartilaginous fish to mammals. This region, which covers over two megabases in the mammals where it has been studied [1], contains a large multigene family that encodes the membranebound glycoproteins known as MHC molecules
Certain residues are CD94L-specific, and others are homogenised within species To investigate the evolutionary relationship between the CD94L and class Ia loci, we searched the nucleotide database to identify species in which sequences were available covering the whole extracellular portions of both CD94L and class Ia molecules
Summary
Whether MHC molecules undergo concerted evolution or not has been the subject of a longstanding debate. A major histocompatibility complex (MHC) is found in the genome of all vertebrates from cartilaginous fish to mammals This region, which covers over two megabases in the mammals where it has been studied [1], contains a large multigene family that encodes the membranebound glycoproteins known as MHC molecules. According to the 'birth and death' model, this reflects the propensity of MHC molecules to derive from a single ancestral sequence by successive gene duplications. Another explanation, the 'concerted evolution' model, is that class Ia and class Ib molecules tend to become like each other due to frequent events of gene conversion, without necessarily deriving from a single sequence
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