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

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 1992 Jun 1

PMID 1644282

Citations 2513

Authors

L Excoffier

P E Smouse

J M Quattro

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Genetic characteristics of endemic Prunus tomentosa in China based on microsatellites.

Wan T, Zhou J, Yin X, An F, Qiao B, Yan Z BMC Plant Biol. 2025; 25(1):309.

PMID: 40069666 PMC: 11895182. DOI: 10.1186/s12870-025-06324-0.

Migration of wheat stripe rust from the primary oversummering region to neighboring regions in China.

Li Y, Zhang S, Liu D, Zhang T, Zhang Z, Zhao J Commun Biol. 2025; 8(1):350.

PMID: 40033097 PMC: 11876435. DOI: 10.1038/s42003-025-07789-3.

Genetic Variability of Dalbulus maidis Populations from Brazil and Their Infectivity with Pathogens of Corn Stunt Complex.

Gorayeb E, do Nascimento S, Ferreira J, de Oliveira V, Savaris D, Dos Santos Carbonari L Neotrop Entomol. 2025; 54(1):44.

PMID: 40014204 DOI: 10.1007/s13744-025-01257-7.

Evidence for Pathogen-Driven Selection Acting on in Response to Malaria in West Africa.

Goeury T, Faye N, Gerbault P, cerny V, Crubezy E, Chiaroni J Ecol Evol. 2025; 15(2):e70933.

PMID: 40008064 PMC: 11850448. DOI: 10.1002/ece3.70933.

Genetic diversity, population structure in a historical panel of Brazilian soybean cultivars.

Silva A, Gregorio da Silva D, Ferreira E, Abdelnoor R, Borem A, Arias C PLoS One. 2025; 20(1):e0313151.

PMID: 39883624 PMC: 11781709. DOI: 10.1371/journal.pone.0313151.

References

Barbujani G, Sokal R . Genetic population structure of Italy. II. Physical and cultural barriers to gene flow. Am J Hum Genet. 1991; 48(2):398-411. PMC: 1683007. View

Nei M, Miller J . A simple method for estimating average number of nucleotide substitutions within and between populations from restriction data. Genetics. 1990; 125(4):873-9. PMC: 1204113. DOI: 10.1093/genetics/125.4.873. View

Semino O, Torroni A, Scozzari R, Brega A, De Benedictis G, Santachiara Benerecetti A . Mitochondrial DNA polymorphisms in Italy. III. Population data from Sicily: a possible quantitation of maternal African ancestry. Ann Hum Genet. 1989; 53(2):193-202. DOI: 10.1111/j.1469-1809.1989.tb01784.x. View

Birky Jr C, Fuerst P, Maruyama T . Organelle gene diversity under migration, mutation, and drift: equilibrium expectations, approach to equilibrium, effects of heteroplasmic cells, and comparison to nuclear genes. Genetics. 1989; 121(3):613-27. PMC: 1203645. DOI: 10.1093/genetics/121.3.613. View

Brega A, Gardella R, Semino O, Morpurgo G, Astaldi Ricotti G, Wallace D . Genetic studies on the Tharu population of Nepal: restriction endonuclease polymorphisms of mitochondrial DNA. Am J Hum Genet. 1986; 39(4):502-12. PMC: 1683983. View

Scozzari R, Torroni A, Semino O, Sirugo G, Brega A, Santachiara-Benerecetti A . Genetic studies on the Senegal population. I. Mitochondrial DNA polymorphisms. Am J Hum Genet. 1988; 43(4):534-44. PMC: 1715495. View

Vilkki J, Savontaus M, Nikoskelainen E . Human mitochondrial DNA types in Finland. Hum Genet. 1988; 80(4):317-21. DOI: 10.1007/BF00273643. View

Wallace D, Garrison K, Knowler W . Dramatic founder effects in Amerindian mitochondrial DNAs. Am J Phys Anthropol. 1985; 68(2):149-55. DOI: 10.1002/ajpa.1330680202. View

Bonne-Tamir B, Johnson M, Natali A, Wallace D, Cavalli-Sforza L . Human mitochondrial DNA types in two Israeli populations--a comparative study at the DNA level. Am J Hum Genet. 1986; 38(3):341-51. PMC: 1684768. View

10.

Cann R, Stoneking M, Wilson A . Mitochondrial DNA and human evolution. Nature. 1987; 325(6099):31-6. DOI: 10.1038/325031a0. View

11.

Felsenstein J . Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet. 1988; 22:521-65. DOI: 10.1146/annurev.ge.22.120188.002513. View

12.

Slatkin M . The average number of sites separating DNA sequences drawn from a subdivided population. Theor Popul Biol. 1987; 32(1):42-9. DOI: 10.1016/0040-5809(87)90038-4. View

13.

Long J, Smouse P, Wood J . The allelic correlation structure of Gainj- and Kalam-speaking people. II. The genetic distance between population subdivisions. Genetics. 1987; 117(2):273-83. PMC: 1203203. DOI: 10.1093/genetics/117.2.273. View

14.

Long J . The allelic correlation structure of Gainj- and Kalam-speaking people. I. The estimation and interpretation of Wright's F-statistics. Genetics. 1986; 112(3):629-47. PMC: 1202767. DOI: 10.1093/genetics/112.3.629. View

15.

Nei M . Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci U S A. 1973; 70(12):3321-3. PMC: 427228. DOI: 10.1073/pnas.70.12.3321. View

16.

Mantel N . The detection of disease clustering and a generalized regression approach. Cancer Res. 1967; 27(2):209-20. View

17.

Giles R, Blanc H, Cann H, Wallace D . Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A. 1980; 77(11):6715-9. PMC: 350359. DOI: 10.1073/pnas.77.11.6715. View

18.

Nei M, Tajima F . DNA polymorphism detectable by restriction endonucleases. Genetics. 1981; 97(1):145-63. PMC: 1214380. DOI: 10.1093/genetics/97.1.145. View

19.

Ewens W, Spielman R, Harris H . Estimation of genetic variation at the DNA level from restriction endonuclease data. Proc Natl Acad Sci U S A. 1981; 78(6):3748-50. PMC: 319649. DOI: 10.1073/pnas.78.6.3748. View

20.

Brown W, Prager E, Wang A, Wilson A . Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol. 1982; 18(4):225-39. DOI: 10.1007/BF01734101. View