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MBE Advance Access published online on September 6, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl106
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted August 28, 2006

Research Article

Robustness of Coalescent Estimators to Between-Lineage Mutation Rate Variation

Mary K. Kuhner 1 *

1 Department of Genome Sciences, University of Washington Seattle

* To whom correspondence should be addressed.
Mary K. Kuhner, E-mail: mkkuhner{at}gs.washington.edu


  Abstract

Data from HIV and from human neoplastic cells can show substantial between-lineage mutation rate variation even within a single population. Such variation may affect estimators of population quantities such as {Theta} = 4Neµ. Using simulated DNA data, I measured the effect of rate variation on recovery of {Theta} by the summary-statistic estimator of Watterson (1975) and the coalescent maximum likelihood algorithm LAMARC (Kuhner 2006). Watterson's estimator showed a downward bias, as expected, with high values of {Theta}. LAMARC's mean estimate was accurate for all tested values of {Theta} and rate variation except for a downward bias when rate variation was maximal (i.e. the slow rate was zero). LAMARC had consistently narrower confidence intervals than Watterson's estimator. Both methods tended to reject the truth too often when rate variation was 8x or greater and independent among branches, as well as when variation was 4x or greater and correlated among branches. In the case of Watterson's estimate this excess rejection was fully attributable to variation among genealogies in the amount of total branch length associated with the fast and slow rates. However, in the case of LAMARC some excess rejection was still observed even when between-genealogy variation was taken into account. Both estimators are robust to modest rate variation; however, their use should be coupled with a statistical test to rule out extreme rate variation as the resulting confidence intervals may not be reliable.

Keywords: coalescent; mutation rate variation; maximum likelihood.
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