NDLI: Heterogeneity of $${\varvec{\rm d}}{\varvec{N}}/{\varvec{\rm d}}{\varvec{S}}$$ Ratios at the Classical HLA Class I Genes over Divergence Time and Across the Allelic Phylogeny

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Heterogeneity of $${\varvec{\rm d}}{\varvec{N}}/{\varvec{\rm d}}{\varvec{S}}$$ Ratios at the Classical HLA Class I Genes over Divergence Time and Across the Allelic Phylogeny

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Heterogeneity of $${\varvec{\rm d}}{\varvec{N}}/{\varvec{\rm d}}{\varvec{S}}$$ Ratios at the Classical HLA Class I Genes over Divergence Time and Across the Allelic Phylogeny

Content Provider	Springer Nature Link
Author	Bitarello, Bárbara Domingues Francisco, Rodrigo dos Santos Meyer, Diogo
Copyright Year	2015
Abstract	The classical class I HLA loci of humans show an excess of nonsynonymous with respect to synonymous substitutions at codons of the antigen recognition site (ARS), a hallmark of adaptive evolution. Additionally, high polymporphism, linkage disequilibrium, and disease associations suggest that one or more balancing selection regimes have acted upon these genes. However, several questions about these selective regimes remain open. First, it is unclear if stronger evidence for selection on deep timescales is due to changes in the intensity of selection over time or to a lack of power of most methods to detect selection on recent timescales. Another question concerns the functional entities which define the selected phenotype. While most analyses focus on selection acting on individual alleles, it is also plausible that phylogenetically defined groups of alleles (“lineages”) are targets of selection. To address these questions, we analyzed how $${\mathrm{d}}N/{\mathrm{d}}S$$ ( $$\omega$$ ) varies with respect to divergence times between alleles and phylogenetic placement (position of branches). We find that $$\omega$$ for ARS codons of class I HLA genes increases with divergence time and is higher for inter-lineage branches. Throughout our analyses, we used non-selected codons to control for possible effects of inflation of $$\omega$$ associated to intra-specific analysis, and showed that our results are not artifactual. Our findings indicate the importance of considering the timescale effect when analysing $$\omega$$ over a wide spectrum of divergences. Finally, our results support the divergent allele advantage model, whereby heterozygotes with more divergent alleles have higher fitness than those carrying similar alleles.
Starting Page	38
Ending Page	50
Page Count	13
File Format	PDF
ISSN	00222844
Journal	Journal of Molecular Evolution
Volume Number	82
Issue Number	1
e-ISSN	14321432
Language	English
Publisher	Springer US
Publisher Date	2015-11-14
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Balancing selection HLA MHC $${\mathrm{d}}N/{\mathrm{d}}S$$ Allelic lineages Antigen recognition site Divergent allele advantage Evolutionary Biology Microbiology Plant Sciences Plant Genetics & Genomics Animal Genetics and Genomics Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics

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