Aditya Kashyap, Maria Anna Rapsomaniki, et al.
TIBTECH
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 inthis regionare 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. Copyright © 2008 by the Genetics Society of America.
Aditya Kashyap, Maria Anna Rapsomaniki, et al.
TIBTECH
Raúl Fernández Díaz, Lam Thanh Hoang, et al.
ICLR 2025
Jason Hindes, Simone Bianco, et al.
PLoS ONE
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MRS Spring Meeting 2023