Intron length and accelerated 3' gene evolution.
Genetic evolution depends in part upon a balance between negative selection and environmentally driven mutation. To explore whether this balance is affected by gene structure, we have used phylogenetic data mining to compare gene compositions across a range of species. Here we show that genomes of higher species exhibit a greater frequency of 5' CpG islands and of CpG-->TpG/CpA transitions. This latter mutational pattern exhibits a 5'-to-3' trend in higher species, consistent with a length-dependent effect on methylation-dependent CpG suppression. Associated strand asymmetry (TpG>CpA) declines with gene length, implying attenuation of transcription-coupled repair 3' to introns. A sharp 3' rise in coding region single-nucleotide polymorphism frequency further supports a mechanistic role for intron length in promoting genetic variation by reducing repair and/or weakening negative selection. Consistent with this, the Ka/Ks ratio of 3' exons exceeds that of centrally located exons in intron-containing, but not in intronless, genes (p<0.0003). We conclude that the efficiency of transcription-coupled repair decreases with gene length, suggesting in turn that 3' gene evolution is accelerated both by introns and by gene methylation.
Tang
Clara S
CS
Laboratory of Computational Oncology, Department of Medicine, Pokfulam, Hong Kong.
Zhao
Yong Z
YZ
Laboratory of Computational Oncology, Department of Medicine, Pokfulam, Hong Kong.
Smith
David K
DK
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
Epstein
Richard J
RJ
Laboratory of Computational Oncology, Department of Medicine, Pokfulam, Hong Kong. Electronic address: repstein@hku.hk.
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair; D015226:Dinucleoside Phosphates / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005796:Genes; D006801:Humans; D007438:Introns / Q000235:genetics*; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity; D014158:Transcription, Genetic; D015027:Zebrafish / Q000235:genetics
D020413:3' Untranslated Regions; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide