Journal Article

Conservation of Neutral Substitution Rate and Substitutional Asymmetries in Mammalian Genes

C. F. Mugal, J. B. W. Wolf, H. H. von Grünberg and H. Ellegren

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 2, issue , pages 19-28
Published in print January 2010 |
Published online January 2010 | e-ISSN: 1759-6653 | DOI: http://dx.doi.org/10.1093/gbe/evp056

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Local variation in neutral substitution rate across mammalian genomes is governed by several factors, including sequence context variables and structural variables. In addition, the interplay of replication and transcription, known to induce a strand bias in mutation rate, gives rise to variation in substitutional strand asymmetries. Here, we address the conservation of variation in mutation rate and substitutional strand asymmetries using primate- and rodent-specific repeat elements located within the introns of protein-coding genes. We find significant but weak conservation of local mutation rates between human and mouse orthologs. Likewise, substitutional strand asymmetries are conserved between human and mouse, where substitution rate asymmetries show a higher degree of conservation than mutation rate. Moreover, we provide evidence that replication and transcription are correlated to the strength of substitutional asymmetries. The effect of transcription is particularly visible for genes with highly conserved gene expression. In comparison with replication and transcription, mutation rate influences the strength of substitutional asymmetries only marginally.

Keywords: neutral substitution rate; substitutional strand asymmetries; transcription-induced mutation; gene expression conservation

Journal Article.  6328 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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