Genome Biology and Evolution Advance Access published online on April 30, 2009
Genome Biology and Evolution, doi:10.1093/gbe/evp001
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Evidence that replication-associated mutation alone does not explain between-chromosome differences in substitution rates
1 Department of Biology and Biochemistry, University of Bath, Bath, Somerset, BA2 7AY, UK
2 Present address: Biotechnology and Toxicology Division, Environment Protection Training and Research Institute, 91/4, Gachibowli, Hyderabad – 500 032, Andhra Pradesh, India
3 The Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK
4 Present address: EMBL-European Bioinformatics Institute, Cambridge, CB10 1SD, UK
5 Present address: John Innes Centre, Norwich Research Park, Colney, Norwich, NR4 7UH, UK
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Abstract |
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Since Haldane first noticed an excess of paternally-derived mutations, it has been considered that most mutations derive from errors during germline replication. Miyata et al. proposed that differences in the rate of neutral evolution on X, Y and autosome can be employed to measure the extent of this male-bias. This commonly applied method assumes replication to be the sole source of between-chromosome variation in substitution rates. We propose a simple test of this assumption: if true, estimates of the male-bias should be independent of which two chromosomal classes are compared. Prior evidence from rodents suggested that this might not be true but conclusions were limited by a lack of rat Y-linked sequence. We therefore sequenced two rat Y-linked BACs and determined evolutionary rate by comparison with mouse. For estimation of rates we consider both introns and synonymous rates. Surprisingly, for both data sets the prediction of congruent estimates of alpha is strongly rejected. Indeed, some comparisons suggest a female-bias, with autosomes evolving faster than Y-linked sequence. We conclude that the method of Miyata et al. has the potential to provide incorrect estimates. Correcting the method requires understanding of the other causes of substitution that might differ between chromosomal classes. One possible cause is recombination-associated substitution bias for which we find evidence. We note that if, as some suggest, this association is dominantly owing to male recombination, the high estimates of alpha seen in birds is to be expected as Z chromosomes recombine in males.
Received January 13, 2009; Revised February 26, 2009; Accepted March 5, 2009