Mutations as missing data: Inferences on the ages and distributions of nonsynonymous and synonymous mutations

Authors
Citation
R. Nielsen, Mutations as missing data: Inferences on the ages and distributions of nonsynonymous and synonymous mutations, GENETICS, 159(1), 2001, pp. 401-411
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Molecular Biology & Genetics
Journal title
GENETICS
ISSN journal
0016-6731 → ACNP
Volume
159
Issue
1
Year of publication
2001
Pages
401 - 411
Database
ISI
SICI code
0016-6731(200109)159:1<401:MAMDIO>2.0.ZU;2-Y
Abstract
This article describes a new Markov chain Monte Carlo (MCMC) method applica ble to DNA sequence data, which treats mutations in the genealogy as missin g data. The method facilitates inferences regarding the age and identity of specific mutations while taking the full complexities of the mutational pr ocess in DNA sequences into account. We demonstrate the utility of the meth od in three applications. First, we demonstrate how the method can be used to make inferences regarding population genetical parameters such as theta (the effective population size times the mutation rate). Second, we show ho w the method can be used to estimate the ages of mutations in finite sites models and for making inferences regarding the distribution and ages of non synonymous and synonymous mutations. The method is applied to two previousl y published data sets and we demonstrate that in one of the data sets the a verage age of nonsynonymous mutations is significantly, lower than the aver age age of synonymous mutations, suggesting the presence of slightly delete rious mutations. Third, we demonstrate how the method in general can be use d to evaluate the posterior distribution of a function of a mapping of muta tions on a gene genealogy. This application is useful for evaluating the un certainty associated with methods that rely on mapping mutations on a phylo geny or a gene genealogy.