Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genetics. 2008 Nov;180(3):1511-24. doi: 10.1534/genetics.108.091116. Epub 2008 Sep 14.

Maximum-likelihood estimation of site-specific mutation rates in human mitochondrial DNA from partial phylogenetic classification.

Author information

  • 1Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel. saharon@post.tau.ac.il

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-I, 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.

PMID:
18791242
[PubMed - indexed for MEDLINE]
PMCID:
PMC2581953
Free PMC Article

Images from this publication.See all images (6)Free text

F igure  1.—
F igure  2.—
F igure  3.—
F igure  4.—
F igure  5.—
F igure  6.—
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk