Journal of Heredity Advance Access published online on April 16, 2007
Journal of Heredity, doi:10.1093/jhered/esm017
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Elevated Basal Slippage Mutation Rates among the Canidae
From the Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390 (Laidlaw, Ng, Garner, and Fondon); the Laboratory for Biocomputing and Informatics, Department of Computer Science, Boston University, Boston, MA 02215 (Gelfand and Benson); the McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX 75390 (Ng and Garner); and the Howard Hughes Medical Institute and Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390 (Ranganathan)
Address correspondence to John W. Fondon III at the address above, or e-mail: john.fondon{at}utsouthwestern.edu
The remarkable responsiveness of dog morphology to selection is a testament to the mutability of mammals. The genetic sources of this morphological variation are largely unknown, but some portion is due to tandem repeat length variation in genes involved in development. Previous analysis of tandem repeats in coding regions of developmental genes revealed fewer interruptions in repeat sequences in dogs than in the orthologous repeats in humans, as well as higher levels of polymorphism, but the fragmentary nature of the available dog genome sequence thwarted attempts to distinguish between locus-specific and genome-wide origins of this disparity. Using whole-genome analyses of the human and recently completed dog genomes, we show that dogs possess a genome-wide increase in the basal germ-line slippage mutation rate. Building on the approach that gave rise to the initial observation in dogs, we sequenced 55 coding repeat regions in 42 species representing 10 major carnivore clades and found that a genome-wide elevated slippage mutation rate is a derived character shared by diverse wild canids, distinguishing them from other Carnivora. A similarly heightened slippage profile was also detected in rodents, another taxon exhibiting high diversity and rapid evolvability. The correlation of enhanced slippage rates with major evolutionary radiations suggests that the possession of a "slippery" genome may bestow on some taxa greater potential for rapid evolutionary change.
Corresponding Editor: Elaine Ostrander