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Genetics, Vol 131, 479-491, Copyright © 1992

INVESTIGATIONS

Analysis of Molecular Variance Inferred From Metric Distances Among DNA Haplotypes: Application to Human Mitochondrial DNA Restriction Data

L. Excoffier, P. E. Smouse and J. M. Quattro
Center for Theoretical and Applied Genetics (CTAG), Cook College, Rutgers University, New Brunswick, New Jersey 08903-0231, Department of Anthropology and Ecology, University of Geneva, 1227 Carouge, Switzerland

We present here a framework for the study of molecular variation within a single species. Information on DNA haplotype divergence is incorporated into an analysis of variance format, derived from a matrix of squared-distances among all pairs of haplotypes. This analysis of molecular variance (AMOVA) produces estimates of variance components and F-statistic analogs, designated here as {phi}-statistics, reflecting the correlation of haplotypic diversity at different levels of hierarchical subdivision. The method is flexible enough to accommodate several alternative input matrices, corresponding to different types of molecular data, as well as different types of evolutionary assumptions, without modifying the basic structure of the analysis. The significance of the variance components and {phi}-statistics is tested using a permutational approach, eliminating the normality assumption that is conventional for analysis of variance but inappropriate for molecular data. Application of AMOVA to human mitochondrial DNA haplotype data shows that population subdivisions are better resolved when some measure of molecular differences among haplotypes is introduced into the analysis. At the intraspecific level, however, the additional information provided by knowing the exact phylogenetic relations among haplotypes or by a nonlinear translation of restriction-site change into nucleotide diversity does not significantly modify the inferred population genetic structure. Monte Carlo studies show that site sampling does not fundamentally affect the significance of the molecular variance components. The AMOVA treatment is easily extended in several different directions and it constitutes a coherent and flexible framework for the statistical analysis of molecular data.


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