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Title: GENOMIC DIVERGENCES AMONG CATTLE, DOG, AND HUMAN ESTIMATED FROM LARGE-SCALE ALIGNMENTS OF GENOMIC SEQUENCES

Author
item Liu, Ge - George
item Van Tassell, Curtis - Curt
item Sonstegard, Tad
item MATUKUMALLI, LAKSHMI - GEORGE MASON UNIVERSITY
item Shade, Larry

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/7/2006
Publication Date: 6/7/2006
Citation: Liu, G., Van Tassell, C.P., Sonstegard, T.S., Matukumalli, L.K., Shade, L.L. 2006. Genomic divergences among cattle, dog, and human estimated from large-scale alignments of genomic sequences. Biomed Central (BMC) Genomics. 7(1):140.

Interpretive Summary: We performed a detailed analysis to determine differences in the rate of genomic divergence by the large-scale comparison of 11 million bases of genomic sequence from cattle, human and dog. The work provides data to suggest that mutation rate has varied for different sequence classes and among genomic regions in mammalian species. Using the human and dog genome assemblies as references, optimal 3-way global alignments were constructed for 84 cattle large (>50,000 bases) genomic sequence clones or loci. Whereas overall genomic divergences remain relatively constant (32-36%), mutation rates (1.9-2.0 x 10(-9) substitutions/site/year) vary among mammalian lineages. Relative rate tests demonstrated cattle had a faster mutation rate when compared to the dog and the difference was about 6%. Mutation rates at different regions in the genome were examined for various sequence classes under different functional constraints. A slightly higher average mutation rate was detected in regions containing duplicated sequences, while the average mutation rates in areas responsible for coding genes are only half of the overall rates. Knowledge of mutation rates is crucial for building an evolutionary timescale, discovering conserved functional elements that do not actually encode genes, identifying genetic novelty like positive selection, and understanding inheritable diseases. The results of this work provide fundamental details regarding genomic divergences over evolutionary time and have broad impact to evolutionary biology, genomics, genetics and animal science.

Technical Abstract: We performed a detailed analysis of genomic divergences based on large-scale comparison of 11 Mb of genomic sequence from cattle, human and dog. Using human and dog genome assemblies as references, optimal 3-way global alignments were constructed for 84 cattle large (>50 kb) genomic sequence clones or loci. Whereas overall genomic divergences remain relatively constant (32-36%), mutation rates (1.9-2.0 x 10(-9) substitutions/site/year) vary among mammalian lineages. Relative rate tests demonstrated cattle had faster rates of substitution when compared to dog and the difference was about 6%. Regional variation in mutation rates was examined for various sequence classes under different functional constraints. A slightly higher average mutation rate was detected in repetitive sequences, while the average mutation rates in coding genes are only half of the overall rates. Assuming that the genome sequence we have sampled is representative, our data indicate that mutation rate has varied for different sequence class and among genomic regions in mammalian species.