Functional divergence in oligopeptide transporters in plants

Abstract Human leukocyte antigen (HLA) genes are among the most polymorphic of our genome, as a likely consequence of balancing selection related to their central role in adaptive immunity. HLA-A and HLA-B genes were recently suggested to evolve through a model of joint divergent asymmetric selection conferring all populations, including those with severe loss of diversity, an equivalent immune potential. However, the mechanisms by which these two genes might undergo joint evolution while displaying very distinct allelic profiles in populations worldwide are still unknown. To address this issue, we carried out extensive data analyses (among which factorial correspondence and linear modelling) on 2,909 common and rare HLA-A, HLA-B and HLA-C alleles and 200,000 simulated pathogenic peptides by taking into account sequence variation, predicted peptide-binding affinity and HLA allele frequencies in 123 populations worldwide. Our results show that HLA-A and HLA-B (but not HLA-C) molecules maintain considerable functional divergence in almost all populations, which likely plays an instrumental role in their immune defence. We also provide robust evidence of functional complementarity between HLA-A and HLA-B molecules, which display asymmetric relationships in terms of amino acid diversity at both inter- and intra-protein levels and in terms of promiscuous or fastidious peptide-binding specificities. Like two wings of a flying bird, the functional complementarity of HLA-A and HLA-B is a perfect example, in our genome, of duplicated genes sharing their capacity of assuming common vital functions while being submitted to complex and sometimes distinct environmental pressures.

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Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence

International Journal of Molecular Sciences ◽

10.3390/ijms22063012 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3012

Author(s):

James I. Mitchell-White ◽

Thomas Stockner ◽

Nicholas Holliday ◽

Stephen J. Briddon ◽

Ian D. Kerr

Keyword(s):

Substrate Specificity ◽

Functional Divergence ◽

3D Structure ◽

Sequence Divergence ◽

Conformational Flexibility ◽

Substrate Selectivity ◽

Multiple Sequence ◽

Atp Binding Cassette Transporters ◽

Structural Network ◽

Wide Substrate Specificity

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.

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Elevated Evolutionary Rates among Functionally Diverged Reproductive Genes across Deep Vertebrate Lineages

International Journal of Evolutionary Biology ◽

10.4061/2011/274975 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Christopher J. Grassa ◽

Rob J. Kulathinal

Keyword(s):

Gene Ontology ◽

Comparative Genomics ◽

Danio Rerio ◽

Mus Musculus ◽

Functional Divergence ◽

Anolis Carolinensis ◽

Egg Laying ◽

Reproductive Systems ◽

Evolutionary Patterns ◽

Reproductive Genes

Among closely related taxa, proteins involved in reproduction generally evolve more rapidly than other proteins. Here, we apply a functional and comparative genomics approach to compare functional divergence across a deep phylogenetic array of egg-laying and live-bearing vertebrate taxa. We aligned and annotated a set of 4,986 1 : 1 : 1 : 1 : 1 orthologs in Anolis carolinensis (green lizard), Danio rerio (zebrafish), Xenopus tropicalis (frog), Gallus gallus (chicken), and Mus musculus (mouse) according to function using ESTs from available reproductive (including testis and ovary) and non-reproductive tissues as well as Gene Ontology. For each species lineage, genes were further classified as tissue-specific (found in a single tissue) or tissue-expressed (found in multiple tissues). Within independent vertebrate lineages, we generally find that gonadal-specific genes evolve at a faster rate than gonadal-expressed genes and significantly faster than non-reproductive genes. Among the gonadal set, testis genes are generally more diverged than ovary genes. Surprisingly, an opposite but nonsignificant pattern is found among the subset of orthologs that remained functionally conserved across all five lineages. These contrasting evolutionary patterns found between functionally diverged and functionally conserved reproductive orthologs provide evidence for pervasive and potentially cryptic lineage-specific selective processes on ancestral reproductive systems in vertebrates.

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