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Journal ArticleDOI

Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection.

01 Oct 1997-Genetics (Genetics Society of America)-Vol. 147, Iss: 2, pp 915-925
TL;DR: It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, Fs, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations.
Abstract: The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, Fs, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li's tests are among the most powerful tests against background selection. Implications of these results are discussed.

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Citations
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Journal ArticleDOI
TL;DR: Arlequin ver 3.0 as discussed by the authors is a software package integrating several basic and advanced methods for population genetics data analysis, like the computation of standard genetic diversity indices, the estimation of allele and haplotype frequencies, tests of departure from linkage equilibrium, departure from selective neutrality and demographic equilibrium, estimation or parameters from past population expansions, and thorough analyses of population subdivision under the AMOVA framework.
Abstract: Arlequin ver 3.0 is a software package integrating several basic and advanced methods for population genetics data analysis, like the computation of standard genetic diversity indices, the estimation of allele and haplotype frequencies, tests of departure from linkage equilibrium, departure from selective neutrality and demographic equilibrium, estimation or parameters from past population expansions, and thorough analyses of population subdivision under the AMOVA framework. Arlequin 3 introduces a completely new graphical interface written in C++, a more robust semantic analysis of input files, and two new methods: a Bayesian estimation of gametic phase from multi-locus genotypes, and an estimation of the parameters of an instantaneous spatial expansion from DNA sequence polymorphism. Arlequin can handle several data types like DNA sequences, microsatellite data, or standard multi-locus genotypes. A Windows version of the software is freely available on http://cmpg.unibe.ch/software/arlequin3.

14,271 citations

Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal ArticleDOI
TL;DR: The present version of DnaSP introduces several new modules and features which, among other options, allow handling big data sets and conducting a large number of coalescent-based tests by Monte Carlo computer simulations.
Abstract: Summary: DnaSP is a software package for the analysis of DNA polymorphism data. Present version introduces several new modules and features which, among other options allow: (1) handling big data sets (∼5 Mb per sequence); (2) conducting a large number of coalescent-based tests by Monte Carlo computer simulations; (3) extensive analyses of the genetic differentiation and gene flow among populations; (4) analysing the evolutionary pattern of preferred and unpreferred codons; (5) generating graphical outputs for an easy visualization of results. Availability: The software package, including complete documentation and examples, is freely available to academic users from: http://www.ub.es/dnasp

6,100 citations


Cites background from "Statistical tests of neutrality of ..."

  • ...…most of the developed neutrality tests (with and without outgroup) and linkage disequilibrium statistics, including—among others—(1) Tajima’s, Fu’s and Fu and Li’s tests (Tajima, 1989; Fu and Li, 1993; Fu, 1997); 2496 Bioinformatics 19(18) © Oxford University Press 2003; all rights reserved....

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Journal ArticleDOI
TL;DR: A critical examination of the neglected biology of mitochondria is carried out and several surprising gaps in the state of the authors' knowledge about this important organelle are pointed out.
Abstract: Mitochondrial DNA (mtDNA) has been used to study molecular ecology and phylogeography for 25 years. Much important information has been gained in this way, but it is time to reflect on the biology of the mitochondrion itself and consider opportunities for evolutionary studies of the organelle itself and its ecology, biochemistry and physiology. This review has four sections. First, we review aspects of the natural history of mitochondria and their DNA to show that it is a unique molecule with specific characteristics that differ from nuclear DNA. We do not attempt to cover the plethora of differences between mitochondrial and nuclear DNA; rather we spotlight differences that can cause significant bias when inferring demographic properties of populations and/or the evolutionary history of species. We focus on recombination, effective population size and mutation rate. Second, we explore some of the difficulties in interpreting phylogeographical data from mtDNA data alone and suggest a broader use of multiple nuclear markers. We argue that mtDNA is not a sufficient marker for phylogeographical studies if the focus of the investigation is the species and not the organelle. We focus on the potential bias caused by introgression. Third, we show that it is not safe to assume a priori that mtDNA evolves as a strictly neutral marker because both direct and indirect selection influence mitochondria. We outline some of the statistical tests of neutrality that can, and should, be applied to mtDNA sequence data prior to making any global statements concerning the history of the organism. We conclude with a critical examination of the neglected biology of mitochondria and point out several surprising gaps in the state of our knowledge about this important organelle. Here we limelight mitochondrial ecology, sexually antagonistic selection, life-history evolution including ageing and disease, and the evolution of mitochondrial inheritance.

2,008 citations


Cites background or methods from "Statistical tests of neutrality of ..."

  • ...Tajima’s D (Tajima 1989), Fu and Li’s D* (Fu & Li 1993), and Fu’s Fs (Fu 1997) can be used to test whether the observed mutation patterns in mtDNA data are consistent with a neutral model of molecular evolution....

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  • ...Tajima’s D (Tajima 1989), Fu and Li’s D* (Fu & Li 1993), and Fu’s Fs (Fu 1997) can be used to test whether...

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Journal ArticleDOI
TL;DR: It is found that, for an extensive variety of cases, the most powerful tests for detecting population growth are Fu's F(S) test and the newly developed R(2) test.
Abstract: A number of statistical tests for detecting population growth are described. We compared the statistical power of these tests with that of others available in the literature. The tests evaluated fall into three categories: those tests based on the distribution of the mutation frequencies, on the haplotype distribution, and on the mismatch distribution. We found that, for an extensive variety of cases, the most powerful tests for detecting population growth are Fu's F(S) test and the newly developed R(2) test. The behavior of the R(2) test is superior for small sample sizes, whereas F(S) is better for large sample sizes. We also show that some popular statistics based on the mismatch distribution are very conservative.

1,929 citations


Cites background or methods or result from "Statistical tests of neutrality of ..."

  • ...…tests using different approaches (e.g., Griffiths and Tavaré 1994; Rogers 1995; Bertorelle and Slatkin 1995; Aris-Brosou and Excoffier 1996; Fu 1996, 1997; Kuhner, Yamato, and Felsenstein 1998; Weiss and Von Haeseler 1998; Galtier, Depaulis, and Barton 2000; Furlong and Brookfield 2001)....

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  • ...Fu (1997) studied the power of some statistics under the logistic model of population growth....

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  • ...Although some authors (Braverman et al. 1995; Simonsen, Churchill, and Aquadro 1995; Fu 1996, 1997) have also investigated the power of some statistical tests against population growth and genetic hitchhiking (which leave similar footprints in DNA sequences) at present there is no exhaustive…...

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  • ...This result agrees with that obtained by Simonsen, Churchill, and Aquadro (1995) and Fu (1997)....

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  • ...We have only studied Fu's FS test statistic (Fu 1997) within this class....

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References
More filters
Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal ArticleDOI
Fumio Tajima1
01 Nov 1989-Genetics
TL;DR: The relationship between the two estimates of genetic variation at the DNA level, namely the number of segregating sites and the average number of nucleotide differences estimated from pairwise comparison, is investigated in this article.
Abstract: The relationship between the two estimates of genetic variation at the DNA level, namely the number of segregating sites and the average number of nucleotide differences estimated from pairwise comparison, is investigated. It is found that the correlation between these two estimates is large when the sample size is small, and decreases slowly as the sample size increases. Using the relationship obtained, a statistical method for testing the neutral mutation hypothesis is developed. This method needs only the data of DNA polymorphism, namely the genetic variation within population at the DNA level. A simple method of computer simulation, that was used in order to obtain the distribution of a new statistic developed, is also presented. Applying this statistical method to the five regions of DNA sequences in Drosophila melanogaster, it is found that large insertion/deletion (greater than 100 bp) is deleterious. It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,417 citations

Journal ArticleDOI
01 Mar 1993-Genetics
TL;DR: From these properties, several new statistical tests based on a random sample of DNA sequences from the population are developed for testing the hypothesis that all mutations at a locus are neutral.
Abstract: Mutations in the genealogy of the sequences in a random sample from a population can be classified as external and internal. External mutations are mutations that occurred in the external branches and internal mutations are mutations that occurred in the internal branches of the genealogy. Under the assumption of selective neutrality, the expected number of external mutations is equal to theta = 4Ne mu, where Ne is the effective population size and mu is the rate of mutation per gene per generation. Interestingly, this expectation is independent of the sample size. The number of external mutations is likely to deviate from its neutral expectation when there is selection while the number of internal mutations is less affected by the presence of selection. Statistical properties of the numbers of external mutations and of internal mutations are studied and their relationships to two commonly used estimates of theta are derived. From these properties, several new statistical tests based on a random sample of DNA sequences from the population are developed for testing the hypothesis that all mutations at a locus are neutral.

3,880 citations

Journal ArticleDOI
TL;DR: The distribution is obtained for the number of segregating sites observed in a sample from a population which is subject to recurring, new, mutations but not subject to recombination, and applies approximately to three population models.

3,870 citations

Journal ArticleDOI
01 Oct 1983-Genetics
TL;DR: These studies indicate that the estimates of the average number of nucleotide differences and nucleon diversity have a large variance, and a large part of this variance is due to stochastic factors.
Abstract: With the aim of analyzing and interpreting data on DNA polymorphism obtained by DNA sequencing or restriction enzyme technique, a mathematical theory on the expected evolutionary relationship among DNA sequences (nucleons) sampled is developed under the assumption that the evolutionary change of nucleons is determined solely by mutation and random genetic drift. The statistical property of the number of nucleotide differences between randomly chosen nucleons and that of heterozygosity or nucleon diversity is investigated using this theory. These studies indicate that the estimates of the average number of nucleotide differences and nucleon diversity have a large variance, and a large part of this variance is due to stochastic factors. Therefore, increasing sample size does not help reduce the variance significantly The distribution of sample allele (nucleomorph) frequencies is also studied, and it is shown that a small number of samples are sufficient in order to know the distribution pattern.

3,038 citations