title: Position-associated GC asymmetry of gene duplicates.
abstract: It is well known that repositioning of a gene often exerts a strong impact on its own expression and whole development. Here we report the results of genome-wide analyses suggesting that repositioning may also radically change the evolutionary fate of gene duplicates. As an indicator of these changes, we used the GC content of gene pairs which originated by duplication. This indicator turned out to be duplicate-asymmetric, which means that genes in a pair differ significantly in GC content despite their apparent origin from a common ancestor. Such an asymmetry necessarily implies that after duplication two originally identical genes mutated in opposite directions-toward GC-rich and GC-poor content, respectively. In mammalian genomes, this trend is definitely associated with presumably methylated hypermutable CpG sites, and in a typical GC-asymmetric gene pair, its two member genes are embedded in GC-contrasting isochores. However, we unexpectedly found similar significant GC asymmetry in fish, fly, worm, and yeast. This means that neither methylation alone nor methylation in combination with isochores can be counted as a primary cause of the GC asymmetry; rather they represent specific realizations of some universal principle of genome evolution. Remarkably, genes from pairs with the greatest GC asymmetry tend to be on different chromosomes, suggesting that the mutational difference between gene duplicates is associated with translocation of a new gene to a different place in the genome, whereas GC symmetric pairs demonstrate the opposite tendency. A recently emerged extra gene copy is usually on the same chromosome as is its parent but quickly, by 0.05 substitution per synonymous site, either has perished or occupies a different chromosome. During this earliest posttranslocation period, the ratio of nonsynonymous/synonymous base substitutions is unusually high, suggesting a rapid adaptive evolution of novel functions. In a general context of evolution by gene duplication, our interpretation of this position-dependent GC asymmetry between duplicated genes is that evolution of redundant genes toward a new function has often been associated with their very early, postduplication repositioning in the genome, with a concomitant abrupt change in epigenetic control of tissue/stage-specific expression and an increase in the mutation rate. Of eight eukaryotic genomes studied, the most distinguished in this respect is the human genome.
authors.affiliation: Department of Theoretical Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. srodin@coh.org
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Rodin
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Parkhomchuk
mesh_terms: D000818:Animals; D001482:Base Composition / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D023061:Gene Order / Q000235:genetics*; D020131:Genes, Duplicate / Q000235:genetics*; D016678:Genome; D023281:Genomics / Q000379:methods; D006801:Humans; D032085:Isochores / Q000235:genetics; D051379:Mice / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010944:Plants / Q000235:genetics; D051381:Rats / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012641:Selection, Genetic; D023741:Takifugu / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D032085:Isochores