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MBE Advance Access first published online on May 9, 2007
This version published online on July 25, 2007

Molecular Biology and Evolution, doi:10.1093/molbev/msm094
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© 2007 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (
http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Research Article

Rates of Genome Evolution and Branching Order from Whole Genome Analysis

Gavin A. Huttley*,1, Matthew J. Wakefield2 and Simon Easteal1

1 John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
2 Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC, 3050, Australia

* Corresponding author Dr Gavin Huttley, John Curtin School of Medical Research, Building 54, The Australian National University, Canberra ACT 0200 Australia, T: 61 2 6125 7961, F: 61 2 6125 2499, E: Gavin.Huttley{at}anu.edu.au

Received for publication March 4, 2007. Revision received May 2, 2007. Accepted for publication May 4, 2007.

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 non-repetitive 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.

Key Words: mutation • substitution rate • male biased evolution • eutherian • phylogeny


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