Rates of genome evolution and branching order from whole genome analysis

Accurate estimation of any phylogeny is important as a framework for evolutionary analysis of form and function at all levels of organization from sequence to whole organism. Using alignments of nonrepetitive components of opossum, human, mouse, rat, and dog genomes we evaluated two alternative tree topologies for eutherian evolution. We show with very high confidence that there is a basal split between rodents (as represented by the mouse and rat) and a branch joining primates (as represented by humans) and carnivores (as represented by dogs), consistent with some but not the most widely accepted mammalian phylogenies. The result was robust to substitution model choice with equivalent inference returned from a spectrum of models ranging from a general time reversible model, a model that treated nucleotides as either purines and pyrimidines, and variants of these that incorporated rate heterogeneity among sites. By determining this particular branching order we are able to show that the rate of molecular evolution is almost identical in rodent and carnivore lineages and that sequences evolve ∼11%-14% faster in these lineages than in the primate lineage. In addition by applying the chicken as outgroup the analyses suggested that the rate of evolution in all eutherian lineages is ∼30% slower than in the opossum lineage. This pattern of relative rates is inconsistent with the hypothesis that generation time is an important determinant of substitution rates and, by implication, mutation rates. Possible factors causing rate differences between the lineages include differences in DNA repair and replication enzymology, and shifts in nucleotide pools. Our analysis demonstrates the importance of using multiple sequences from across the genome to estimate phylogeny and relative evolutionary rate in order to reduce the influence of distorting local effects evident even in relatively long sequences.