Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection

Hughes, Austin L.; Nei, Masatoshi

doi:10.1038/335167a0

Cited by 1,819 publications

(1,247 citation statements)

References 40 publications

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“…Diversifying selection increases nucleotide diversity (π), and an excess of d N to d S is indicative of positive selection favoring amino acid replacement [39]. Thus, the observed excess of d N to d S at nt positions 3000-3600 of clag8 suggests that the polymorphism in clag8 is positively maintained.…”

Section: Diversifying Selection On the Rhoph1/clag Gene Locimentioning

confidence: 99%

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Iriko

Kaneko

Otsuki

et al. 2008

Molecular and Biochemical Parasitology

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A complex of high molecular mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Understanding the level of polymorphism and the evolutionary processes is important for advancements in both vaccine design and knowledge of the evolution of cell invasion in this parasite. In the present study, we sequenced the entire open reading frames of seven genes encoding the proteins of the PfRhopH complex (rhoph2, rhoph3, and five rhoph1/clag gene paralogs). We found that four rhoph1/clag genes (clag2, 3.1, 3.2, and 8) were highly polymorphic. Amino acid substitutions and indels are predominantly clustered around amino acid positions 1000-1200 of these four rhoph1/clag genes. An excess of nonsynonymous substitutions over synonymous substitutions was detected for clag8 and 9, indicating positive selection. The McDonald-Kreitman test with a Plasmodium reichenowi orthologous sequence also supports positive selection on clag8. Based on the ratio of interspecific genetic distance to intraspecific distance, the time to the most recent common ancestor of the clag2 and 8 polymorphisms was estimated to be 1.89 and 0.87 million years ago, respectively, assuming divergence of P. falciparum and P. reichenowi 6 million years ago. In addition to a copy number polymorphism, gene conversion events were detected for the rhoph1/clag genes on chromosome 3, which likely play a role in increasing the diversity of each locus. Our results indicate that a high diversity of the PfRhopH1/Clag multigene family is maintained by diversifying selection forces over a considerably long period.

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Section: Diversifying Selection On the Rhoph1/clag Gene Locimentioning

confidence: 99%

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Iriko

Kaneko

Otsuki

et al. 2008

Molecular and Biochemical Parasitology

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“…33 MEGA 2.0 software was also used to construct the phylogenetic rooted tree based on amino-acidic sequences.…”

Section: Pcr and Sequencingmentioning

confidence: 99%

Evolution of the mannose-binding lectin gene in primates

et al. 2004

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The mannose-binding lectin MBL2 plays an important role in the innate immune system. It binds carbohydrates surface, acts as an opsonin and activates the complement system. With the aim of studying the evolution of the MBL2 gene in primates, we sequenced its coding region in 12 non-human primate species and compared them with the human sequence. We demonstrated that nucleotide and amino-acidic sequences of the MBL2 among primates are highly homologous, underlining the importance of this molecule in the defense system against pathogen invasions. In particular, in the collagen-like domain that confers the characteristic structure to MBL2 protein, the identity among primates is really high. In the carbohydrate recognition domain, we evidenced some primates' group-specific amino-acidic mutations not resulting in changes of the structure or function of this MBL2 domain. Phylogenetic analysis did not evidence any positive selective pressure in MBL2 gene among non-human primates. Our findings indicate that MBL2 is well conserved in agreement with its important role in the immune system: in non-human primates, we did not observe the same 'plasticity' of the MBL2 human gene, where a frequency of more than 1% of nucleotide variations was described in the coding and promoter regions.

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“…Further, patterns of mutational substitutions within the PBR have affirmed the strong role of historic selection pressures in preserving functional variation, likely with peptide binding consequences, for this region. 8,[11][12][13] To date there are some 108 HLA-A, 223 HLA-B and 67 HLA-C alleles which have been classified into groups or families on the basis of serological reactivity. 14 For example, HLA-A alleles separate into six serological families; A1/3/11, A9, A2/28, A10, A19 15 and A80.…”

Section: Correspondence: Stephen J O'brien Phd Laboratory Of Genomimentioning

confidence: 99%

Taxonomic hierarchy of HLA class I allele sequences

et al. 1999

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The markedly high levels of polymorphism present in classical class I loci of the human major histocompatibility complex have been implicated in infectious and immune disease recognition. The large numbers of alleles present at these loci have, however, limited efforts to verify associations between individual alleles and specific diseases. As an approach to reduce allele diversity to hierarchical evolutionarily related groups, we performed phylogenetic analyses of available HLA-A, B and C allele complete sequences (n = 216 alleles) using different approaches (maximum parsimony, distance-based minimum evolution and maximum likelihood). Full nucleotide and amino acid sequences were considered as well as abridged sequences from the hypervariable peptide binding region, known to interact in vivo, with HLA presented foreign peptide. The consensus analyses revealed robust clusters of 36 HLA-C alleles concordant for full and PBR sequence analyses. HLA-A alleles (n = 60) assorted into 12 groups based on full nucleotide and amino acid sequence which with few exceptions recapitulated serological groupings, however the patterns were largely discordant with clusters prescribed by PBR sequences. HLA-B which has the most alleles (n = 120) and which unlike HLA-A and -C is thought to be subject to frequent recombinational exchange, showed limited phylogenetic structure consistent with recent selection driven retention of maximum heterozygosity and population diversity. Those allele categories recognized offer an explicit phylogenetic criterion for grouping alleles potentially relevant for epidemiologic associations, for inferring the origin of MHC genome organization, and for comparing functional constraints in peptide presentation of HLA alleles.

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Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection

Cited by 1,819 publications

References 40 publications

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Evolution of the mannose-binding lectin gene in primates

Taxonomic hierarchy of HLA class I allele sequences

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