Maximum-Likelihood Estimation of Demographic Parameters Using the Frequency Spectrum of Unlinked Single-Nucleotide Polymorphisms

• Published in: Genetics (Austin) 2004-11, Vol.168 (3), p.1699-1712
• Main Authors: Adams, Alison M, Hudson, Richard R
• Format: Article
• Language: English
• Subjects: African Americans; Data Interpretation, Statistical; Gene Frequency; Humans; Investigations; Likelihood Functions; Models, Genetic; Polymorphism; Polymorphism, Single Nucleotide; Population genetics
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1534/genetics.104.030171

A maximum-likelihood method for demographic inference is applied to data sets consisting of the frequency spectrum of unlinked single-nucleotide polymorphisms (SNPs). We use simulation analyses to explore the effect of sample size and number of polymorphic sites on both the power to reject the null hypothesis of constant population size and the properties of two- and three-dimensional maximum-likelihood estimators (MLEs). Large amounts of data are required to produce accurate demographic inferences, particularly for scenarios of recent growth. Properties of the MLEs are highly dependent upon the demographic scenario, as estimates improve with a more ancient time of growth onset and smaller degree of growth. Severe episodes of growth lead to an upward bias in the estimates of the current population size, and that bias increases with the magnitude of growth. One data set of African origin supports a model of mild, ancient growth, and another is compatible with both constant population size and a variety of growth scenarios, rejecting greater than fivefold growth beginning >36,000 years ago. Analysis of a data set of European origin indicates a bottlenecked population history, with an 85% population reduction occurring approximately 30,000 years ago.