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- Title
Maximum-Likelihood Estimation of Site-Specific Mutation Rates in Human Mitochondrial DNA From Partial Phylogenetic Classification.
- Authors
Rosset, Saharon; Wells, R. Spencer; Soria-Hernanz, David F.; Tyler-Smith, Chris; Royyuru, Ajay K.; Behar, Doron M.
- Abstract
The mitochondrial DNA hypervariable segment I (HVS-I) is widely used in studies of human evolutionary genetics, and therefore accurate estimates of mutation rates among nucleotide sites in this region are essential. We have developed a novel maximum-likelihood methodology for estimating site-specific mutation rates from partial phylogenetic information, such as haplogroup association. The resulting estimation problem is a generalized linear model, with a nonstandard link function. We develop inference and bias correction tools for our estimates and a hypothesis-testing approach for site independence. We demonstrate our methodology using 16,609 HVS-I samples from the Genographic Project. Our results suggest that mutation rates among nucleotide sites in HVS-I are highly variable. The 16,400-16,500 region exhibits significantly lower rates compared to other regions, suggesting potential functional constraints. Several loci identified in the literature as possible termination-associated sequences (TAS) do not yield statistically slower rates than the rest of HVS-l, casting doubt on their functional importance. Our tests do not reject the null hypothesis of independent mutation rates among nucleotide sites, supporting the use of site-independence assumption for analyzing HVS-I. Potential extensions of our methodology include its application to estimation of mutation rates in other genetic regions, like Y chromosome short tandem repeats.
- Subjects
MITOCHONDRIAL DNA; HUMAN evolution; GENETICS; METHODOLOGY; Y chromosome; BIOLOGICAL evolution
- Publication
Genetics, 2008, Vol 180, Issue 3, p1511
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.108.091116