Natural selection at the class II major histocompatibility complex loci of mammals

Hughes, Austin L.; Hughes, Marianne K.; Howell, Carina Y.; Nei, Masatoshi

doi:10.1007/978-94-009-0077-6_10

Cited by 92 publications

(59 citation statements)

References 29 publications

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“…This pattern is exactly what was observed (Hughes and Nei, 1988). A similar pattern was later observed in the case of class II MHC molecules as well (Hughes et al, 1994).…”

Section: Historical Background Neo-darwinismsupporting

confidence: 88%

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

2007

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Recent years have seen an explosion of interest in evidence for positive Darwinian selection at the molecular level. This quest has been hampered by the use of statistical methods that fail adequately to rule out alternative hypotheses, particularly the relaxation of purifying selection and the effects of population bottlenecks, during which the effectiveness of purifying selection is reduced. A further problem has been the assumption that positive selection will generally involve repeated amino-acid changes to a single protein. This model was derived from the case of the vertebrate major histocompatibility complex (MHC), but the MHC proteins are unusual in being involved in proteinprotein recognition and in a co-evolutionary process of pathogens. There is no reason to suppose that repeated amino-acid changes to a single protein are involved in selectively advantageous phenotypes in general. Rather adaptive phenotypes are much more likely to result from other causes, including single amino-acid changes; deletion or silencing of genes or changes in the pattern of gene expression.

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“…This pattern is exactly what was observed (Hughes and Nei, 1988). A similar pattern was later observed in the case of class II MHC molecules as well (Hughes et al, 1994).…”

Section: Historical Background Neo-darwinismsupporting

confidence: 88%

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

2007

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“…If prior information such as the crystal structure of the protein is available to predict a subset of sites which may be under positive selection, one can focus on those sites. This approach has been taken by Nei (1988, 1989) and Hughes et al (1994) to analyze the PBR in MHC class I and II proteins in humans and mice. The crystal structures (Bjorkman et al 1987a;Brown et al 1993) were used to identify 57 residues in class I proteins and 44 residues in class II proteins, which constitute the PBR.…”

Section: Introductionmentioning

confidence: 99%

Diversifying and Purifying Selection in the Peptide Binding Region of DRB in Mammals

Furlong

Yang

2008

J Mol Evol

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The class II genes of the major histocompatibility complex encode proteins which play a crucial role in antigen presentation. They are among the most polymorphic proteins known, and this polymorphism is thought to be the result of natural selection. To understand the selective pressure acting on the protein and to examine possible differences in the evolutionary dynamics among species, we apply maximum likelihood models of codon substitution to analyze the DRB genes of six mammalian species: human, chimpanzee, macaque, tamarin, dog, and cow. The models account for variable selective pressures across codons in the gene and have the power to detect amino acid residues under either positive or negative selection. Our analysis detected positive selection in the DRB genes in each of the six mammals examined. Comparison with structural data reveals that almost all amino acid residues inferred to be under positive selection in humans are in the peptide binding region (PBR) and are in contact with the antigen side chains, although residues outside of but close to the PBR are also detected. Strong purifying selection is also detected in the PBR, at sites which contact the antigen and at sites which may be involved in dimerization or T cell binding. The analysis demonstrates the utility of the random-sites analysis even when structural information is available. The different mammalian species are found to share many positively or negatively selected sites, suggesting that their functional roles have remained very similar in the different species, despite the different habitats and pathogens of the species.

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“…Most knowledge of the structure and function of MHC genes come from studies in mammals, particularly in humans Nei 1988, 1989;Hughes et al 1994;Parham and Ohta 1996) and many studies in other vertebrates assume that the mechanisms that create and maintain MHC variability are similar across taxa. PBRs, for example, are commonly deduced by comparing MHC sequences from a species of interest with human counterparts (e.g.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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In order to investigate the mechanisms creating and maintaining variability at the major histocompatibility (MH) class II alpha (DAA) locus we examined patterns of polymorphism in two isolated Atlantic salmon populations which share a common post-glacial origin. As expected from their common origin, but contrary to the observation at the MH class I locus, these populations shared the majority of DAA alleles: out of 17 sequences observed, 11 were common to both populations. Recombination seems to play a more important role in the origin of new alleles at the class II alpha locus than at the class I locus. A greater than expected proportion of sites inferred to be positively selected (potentially peptide binding residues, PBRs) were found to be involved in recombination events, suggesting a mechanism for increasing MH variability through an interaction between recombination and natural selection. Thus it appears that although selection and recombination are important mechanisms for the evolution of both class II alpha and class I loci in the Atlantic salmon, the pattern of variability differs markedly between these classes of MH loci.

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Natural selection at the class II major histocompatibility complex loci of mammals

Cited by 92 publications

References 29 publications

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

Diversifying and Purifying Selection in the Peptide Binding Region of DRB in Mammals

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

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