MBE Advance Access originally published online on June 2, 2004
Molecular Biology and Evolution 2004 21(10):1820-1830; doi:10.1093/molbev/msh181
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Research Article |
Gene Expression, Synteny, and Local Similarity in Human Noncoding Mutation Rates
* Department of Evolution, Genomics and Systematics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden; Department of Biology & Biochemistry, University of Bath, Bath, UK
E-mail: matthew.webster{at}ebc.uu.se
The human genome is organized with regard to many features such as isochores, Giemsa bands, clusters of genes with similar expression patterns, and contiguous regions with shared evolutionary histories (synteny blocks). In addition to these genomic features, it is clear that mutation rates also vary across the human genome. To address how mutation rates and genomic features are related, we analyzed substitution rates at three classes of putatively neutral noncoding sites (nongenic, intronic, and ancestral repeats) in 
14 Mb of human–chimpanzee alignments covering human chromosome 7. Patterns of mutation rate variation inferred from substitution rate variation differ among the three site classes. In particular, we find that intronic mutation rates are strongly affected by the breadth of expression of the genes in which they reside, with broadly expressed genes exhibiting low mutation rates, probably as a consequence of the transcription-coupled repair process acting in the germ line. All site classes show significant local similarities in mutation rate at the megabase scale, and regional similarities in nongenic mutation rate covary with blocks of synteny between the human and mouse genomes, indicating that the evolutionary history of a genomic region is an important determinant of mutation rate.
Key Words: human-mouse synteny blocks • gene expression • mutation rate • recombination • gene density • Giemsa bands
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