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Minority of mammalian orthologs can be regarded as physiologically closest genes
Authors:Alexander E. Vinogradov
Affiliation:Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia
Abstract:Orthologs are genes from different genomes that originate from a common ancestor gene by speciation event. They are most similar by the structure of encoded proteins and therefore should have a similar function. Here I apply the principle used for detection of structural orthology for a genome-wide analysis of gene expression. For this purpose, I determine the mutual similarity rank in all-by-all comparison of among-tissues expression patterns. The expression of most part of human–mouse orthologs in homologous tissues is poorly correlated (average mutual coexpression rank is only 4835 out of 18,092). Genes from evolutionarily labile gene families, which experience rapid turnover of family composition, are among those with the strongest expression change. However, the revealed phenomenon is not limited to them. There is no or very weak relationship between protein sequence divergence and mutual coexpression rank. Also, generally there is no relationship between the ratio of nonsynonymous to synonymous nucleotide substitutions and coexpression rank. This relationship is tangible only within evolutionarily labile gene families. These results indicate that despite of a similar biochemical function of orthologs reflected in the conserved protein sequence, the physiological (systemic) context of this function can be changed. Also, these results suggest that gene biochemical function and its physiological role in the organism can evolve independently.
Keywords:Blosum, blocks of amino acid substitution matrix   C2H2, cysteine(2)histidine(2)   COG, clusters of orthologous groups   dN, distance of nonsynonymous substitutions   dS, distance of synonymous substitutions   GPCR, G-protein-coupled receptor   InterPro, integrative protein signature database   KOG, eukaryotic orthologous groups   NCBI, National Center for Biotechnology Information   NOG, non-supervised orthologous groups   PAML, phylogenetic analysis by maximum likelihood   RevTrans, reverse translation alignment program   STRING, search tool for retrieval of interacting genes/proteins
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