Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules.

Hughes, Anthony; Ota, Tomomi; Nei, Masatoshi

doi:10.1093/oxfordjournals.molbev.a040626

Cited by 129 publications

(36 citation statements)

References 22 publications

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“…Indeed, the degree of the polymorphism of Prdm9 is comparable with that of MHC, which may be maintained by selective advantage. 32 Prdm9 polymorphisms converged in the ZF repeats and in amino acid positions at −1, 3, and 6 of the α-helix domain, which are extremely variable and are thought to recognize DNA sequences. A lower level of variation was found for amino acid positions −2 and 1 in both mouse and human ZF repeats.…”

Section: Discussionmentioning

confidence: 99%

Prdm9 Polymorphism Unveils Mouse Evolutionary Tracks

et al. 2014

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PR/SET domain containing 9 (Prdm9) mediates histone modifications such as H3K4me3 and marks hotspots of meiotic recombination. In many mammalian species, the Prdm9 gene is highly polymorphic. Prdm9 polymorphism is assumed to play two critical roles in evolution: to diversify the spectrum of meiotic recombination hotspots and to cause male hybrid sterility, leading to reproductive isolation and speciation. Nevertheless, information about Prdm9 sequences in natural populations is very limited. In this study, we conducted a comprehensive population survey on Prdm9 polymorphism in the house mouse, Mus musculus. Overall M. musculus Prdm9 displays an extraordinarily high level of polymorphism, particularly in regions encoding zinc finger repeats, which recognize recombination hotspots. Prdm9 alleles specific to various M. musculus subspecies dominate in subspecies territories. Moreover, introgression into other subspecies territories was found for highly divergent Prdm9 alleles associated with t-haplotype. The results of our phylogeographical analysis suggest that the requirement for hotspot diversity depends on geographical range and time span in mouse evolution, and that Prdm9 polymorphism has not been maintained by a simple balanced selection in the population of each subspecies.

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Section: Discussionmentioning

confidence: 99%

Prdm9 Polymorphism Unveils Mouse Evolutionary Tracks

et al. 2014

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“…It is also in these domains where the differences between MHC-Ia and MHC-Ib molecules are most apparent. Classical MHC-I proteins are considered the most polymorphic genes in the genome (Trowsdale and Knight 2013) and their polymorphism is primarily restricted to the α1 and α2 domains (Hughes et al 1990). In this manner, different MHC-Ia alleles within a species can present various peptides to T cells and encompass a larger collection of antigens to promote stronger immunity on a population level.…”

Section: The Mr1 Gene and Its Evolutionmentioning

confidence: 99%

Structure and function of the non-classical major histocompatibility complex molecule MR1

Krovi

Gapin

2016

Immunogenetics

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Polymorphic major histocompatibility complex (MHC) molecules play a central role in the vertebrate adaptive immune system. By presenting short peptides derived from pathogen-derived proteins, these “classical” MHC molecules can alert the T cell branch of the immune system of infected cells and clear the pathogen. There exist other “non-classical” MHC molecules, which while similar in structure to classical MHC proteins, are contrasted by their limited polymorphism. While the functions of many class Ib MHC molecules have still to be elucidated, the nature and diversity of antigens (if any) that some of them might present to the immune system is expected to be more restricted and might function as another approach to distinguish self from non-self. The MHC-related 1 (MR1) molecule is a member of this family of non-classical MHC proteins. It was recently shown to present unique antigens in the form of vitamin metabolites found in certain microbes. MR1 is strongly conserved genetically, structurally, and functionally through mammalian evolution, indicating its necessity in ensuring an effective immune system for members of this class. Although MR1 will be celebrating 21 years this year since its discovery, most of our understanding of how this molecule functions has only been uncovered in the past decade. Herein, we discuss where MR1 is expressed, how it selectively is able to bind to its appropriate antigens and how it, then, is able to specifically activate a distinct population of T cells.

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“…For example, tests based on the ratio of nonsynonymous to synonymous sites (dN/dS) have proven to be very useful for detecting selection on amino acid residues that determine binding specificities of proteins that interact with rapidly evolving targets. Well-studied examples include gamete-recognition proteins of free-spawning marine invertebrates [38], [39], proteins involved in immune responses [40], pathogen-recognition proteins in plants [41], and viral epitopes that facilitate escape from the host's immune response and enhance transmission [42], [43]. In these examples, dN/dS ratios are very high because selection drives multiple amino acid replacements within binding sites.…”

Section: Introductionmentioning

confidence: 99%

Detecting Selection in the Blue Crab, Callinectes sapidus, Using DNA Sequence Data from Multiple Nuclear Protein-Coding Genes

Yednock

Neigel

2014

PLoS ONE

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The identification of genes involved in the adaptive evolution of non-model organisms with uncharacterized genomes constitutes a major challenge. This study employed a rigorous and targeted candidate gene approach to test for positive selection on protein-coding genes of the blue crab, Callinectes sapidus. Four genes with putative roles in physiological adaptation to environmental stress were chosen as candidates. A fifth gene not expected to play a role in environmental adaptation was used as a control. Large samples (n>800) of DNA sequences from C. sapidus were used in tests of selective neutrality based on sequence polymorphisms. In combination with these, sequences from the congener C. similis were used in neutrality tests based on interspecific divergence. In multiple tests, significant departures from neutral expectations and indicative of positive selection were found for the candidate gene trehalose 6-phosphate synthase (tps). These departures could not be explained by any of the historical population expansion or bottleneck scenarios that were evaluated in coalescent simulations. Evidence was also found for balancing selection at ATP-synthase subunit 9 (atps) using a maximum likelihood version of the Hudson, Kreitmen, and Aguadé test, and positive selection favoring amino acid replacements within ATP/ADP translocase (ant) was detected using the McDonald-Kreitman test. In contrast, test statistics for the control gene, ribosomal protein L12 (rpl), which presumably has experienced the same demographic effects as the candidate loci, were not significantly different from neutral expectations and could readily be explained by demographic effects. Together, these findings demonstrate the utility of the candidate gene approach for investigating adaptation at the molecular level in a marine invertebrate for which extensive genomic resources are not available.

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Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules.

Cited by 129 publications

References 22 publications

Prdm9 Polymorphism Unveils Mouse Evolutionary Tracks

Prdm9 Polymorphism Unveils Mouse Evolutionary Tracks

Structure and function of the non-classical major histocompatibility complex molecule MR1

Detecting Selection in the Blue Crab, Callinectes sapidus, Using DNA Sequence Data from Multiple Nuclear Protein-Coding Genes

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