Fast rate of evolution in alternatively spliced coding regions of mammalian genes

BACKGROUND: At least half of mammalian genes are alternatively spliced. Alternative isoforms are often genome-specific and it has been suggested that alternative splicing is one of the major mechanisms for generating protein diversity in the course of evolution. Another way of looking at alternative splicing is to consider sequence evolution of constitutive and alternative regions of protein-coding genes. Indeed, it turns out that constitutive and alternative regions evolve in different ways. RESULTS: A set of 3029 orthologous pairs of human and mouse alternatively spliced genes was considered. The rate of nonsynonymous substitutions (d(N)), the rate of synonymous substitutions (d(S)), and their ratio (ω = d(N)/d(S)) appear to be significantly higher in alternatively spliced coding regions compared to constitutive regions. When N-terminal, internal and C-terminal alternatives are analysed separately, C-terminal alternatives appear to make the main contribution to the observed difference. The effects become even more pronounced in a subset of fast evolving genes. CONCLUSION: These results provide evidence of weaker purifying selection and/or stronger positive selection in alternative regions and thus one more confirmation of accelerated evolution in alternative regions. This study corroborates the theory that alternative splicing serves as a testing ground for molecular evolution

Fast rate of evolution in alternatively spliced coding regions of mammalian genes-5

<p><b>Copyright information:</b></p><p>Taken from "Fast rate of evolution in alternatively spliced coding regions of mammalian genes"</p><p>BMC Genomics 2006;7():84-84.</p><p>Published online 18 Apr 2006</p><p>PMCID:PMC1459143.</p><p>Copyright © 2006 Ermakova et al; licensee BioMed Central Ltd.</p>gnments of constitutive regions and of alternative regions both exceeding 80 bp shows that ω tends to be larger in alternative regions. In particular, there are 23 genes with ω-ω0.8. . The distributions of ω-ω, ω-ω, ω-ωfor genes with long N-terminal (1674 genes, top, ω-ω), internal (976 genes, middle, ω-ω), and C-terminal (110 genes, bottom, ω-ω) alternative regions, respectively, show that ωtends to be larger than ωin all types of alternative regions. the grey shadows are symmetrical to the left parts of the histograms

Fast rate of evolution in alternatively spliced coding regions of mammalian genes-2

<p><b>Copyright information:</b></p><p>Taken from "Fast rate of evolution in alternatively spliced coding regions of mammalian genes"</p><p>BMC Genomics 2006;7():84-84.</p><p>Published online 18 Apr 2006</p><p>PMCID:PMC1459143.</p><p>Copyright © 2006 Ermakova et al; licensee BioMed Central Ltd.</p

Fast rate of evolution in alternatively spliced coding regions of mammalian genes-4

<p><b>Copyright information:</b></p><p>Taken from "Fast rate of evolution in alternatively spliced coding regions of mammalian genes"</p><p>BMC Genomics 2006;7():84-84.</p><p>Published online 18 Apr 2006</p><p>PMCID:PMC1459143.</p><p>Copyright © 2006 Ermakova et al; licensee BioMed Central Ltd.</p

Fast rate of evolution in alternatively spliced coding regions of mammalian genes-3

<p><b>Copyright information:</b></p><p>Taken from "Fast rate of evolution in alternatively spliced coding regions of mammalian genes"</p><p>BMC Genomics 2006;7():84-84.</p><p>Published online 18 Apr 2006</p><p>PMCID:PMC1459143.</p><p>Copyright © 2006 Ermakova et al; licensee BioMed Central Ltd.</p

Intergenic, gene terminal, and intragenic CpG islands in the human genome

Abstract Background Recently, it has been discovered that the human genome contains many transcription start sites for non-coding RNA. Regulatory regions related to transcription of this non-coding RNAs are poorly studied. Some of these regulatory regions may be associated with CpG islands located far from transcription start-sites of any protein coding gene. The human genome contains many such CpG islands; however, until now their properties were not systematically studied. Results We studied CpG islands located in different regions of the human genome using methods of bioinformatics and comparative genomics. We have observed that CpG islands have a preference to overlap with exons, including exons located far from transcription start site, but usually extend well into introns. Synonymous substitution rate of CpG-containing codons becomes substantially reduced in regions where CpG islands overlap with protein-coding exons, even if they are located far downstream from transcription start site. CAGE tag analysis displayed frequent transcription start sites in all CpG islands, including those found far from transcription start sites of protein coding genes. Computational prediction and analysis of published ChIP-chip data revealed that CpG islands contain an increased number of sites recognized by Sp1 protein. CpG islands containing more CAGE tags usually also contain more Sp1 binding sites. This is especially relevant for CpG islands located in 3' gene regions. Various examples of transcription, confirmed by mRNAs or ESTs, but with no evidence of protein coding genes, were found in CAGE-enriched CpG islands located far from transcription start site of any known protein coding gene. Conclusions CpG islands located far from transcription start sites of protein coding genes have transcription initiation activity and display Sp1 binding properties. In exons, overlapping with these islands, the synonymous substitution rate of CpG containing codons is decreased. This suggests that these CpG islands are involved in transcription initiation, possibly of some non-coding RNAs.</p