Abstract
BACKGROUND: Approximately 11 Mb of finished high quality genomic sequences were sampled from cattle, dog and human to estimate genomic divergences and their regional variation among these lineages. RESULTS: Optimal three-way multi-species global sequence alignments for 84 cattle clones or loci (each >50 kb of genomic sequence) were constructed using the human and dog genome assemblies as references. Genomic divergences and substitution rates were examined for each clone and for various sequence classes under different functional constraints. Analysis of these alignments revealed that the overall genomic divergences are relatively constant (0.32-0.37 change/site) for pairwise comparisons among cattle, dog and human; however substitution rates vary across genomic regions and among different sequence classes. A neutral mutation rate (2.0-2.2 x 10(-9) change/site/year) was derived from ancestral repetitive sequences, whereas the substitution rate in coding sequences (1.1 x 10(-9) change/site/year) was approximately half of the overall rate (1.9-2.0 x 10(-9) change/site/year). Relative rate tests also indicated that cattle have a significantly faster rate of substitution as compared to dog and that this difference is about 6%. CONCLUSION: This analysis provides a large-scale and unbiased assessment of genomic divergences and regional variation of substitution rates among cattle, dog and human. It is expected that these data will serve as a baseline for future mammalian molecular evolution studies.