scholarly journals Statistical Tests of Neutrality of Mutations Against Population Growth, Hitchhiking and Background Selection

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 915-925 ◽  
Author(s):  
Yun-Xin Fu
Keyword(s):  
Population Growth ◽  
Statistical Tests ◽  
Dna Polymorphisms ◽  
Background Selection ◽  
Genetic Hitchhiking ◽  
Alternative Models ◽  
Tests Of Neutrality ◽  
Rare Alleles

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.

Departure from Neutrality at the Mitochondrial NADH Dehydrogenase Subunit 2 Gene in Humans, but Not in Chimpanzees

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 409-421 ◽  
Author(s):  
Cheryl A Wise ◽  
Michaela Sraml ◽  
Simon Easteal
Keyword(s):  
Nadh Dehydrogenase ◽  
Statistical Tests ◽  
Low Frequency ◽  
Nadh Dehydrogenase Subunit ◽  
Nadh Dehydrogenase Subunit 2 ◽  
Tests Of Neutrality ◽  
Slightly Deleterious Mutations ◽  
Neutral Marker ◽  
Transmembrane Regions ◽  
Interspecific Comparisons

Abstract To test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution, nucleotide sequences were determined for the 1041 bp of the NADH dehydrogenase subunit 2 (ND2) gene in 20 geographically diverse humans and 20 common chimpanzees. Contingency tests of neutrality were performed using four mutational categories for the ND2 molecule: synonymous and nonsynonymous mutations in the transmembrane regions, and synonymous and nonsynonymous mutations in the surface regions. The following three topological mutational categories were also used: intraspecific tips, intraspecific interiors, and interspecific fixed differences. The analyses reveal a significantly greater number of nonsynonymous polymorphisms within human transmembrane regions than expected based on interspecific comparisons, and they are inconsistent with a neutral equilibrium model. This pattern of excess nonsynonymous polymorphism is not seen within chimpanzees. Statistical tests of neutrality, such as Tajima's D test, and the D and F tests proposed by Fu and Li, indicate an excess of low frequency polymorphisms in the human data, but not in the chimpanzee data. This is consistent with recent directional selection, a population bottleneck or background selection of slightly deleterious mutations in human mtDNA samples. The analyses further support the idea that mitochondrial genome evolution is governed by selective forces that have the potential to affect its use as a “neutral” marker in evolutionary and population genetic studies.

scholarly journals Properties of statistical tests of neutrality for DNA polymorphism data.

Genetics ◽  
1995 ◽  
Vol 141 (1) ◽  
pp. 413-429 ◽  
Author(s):  
K L Simonsen ◽  
G A Churchill ◽  
C F Aquadro
Keyword(s):  
Selective Sweep ◽  
Statistical Tests ◽  
Population Bottleneck ◽  
Population Subdivision ◽  
Recent Past ◽  
Molecular Polymorphism ◽  
Tests Of Neutrality ◽  
Long Time ◽  
Alternative Hypotheses ◽  
Polymorphism Data

Abstract A class of statistical tests based on molecular polymorphism data is studied to determine size and power properties. The class includes Tajima's D statistic as well as the D* and F* tests proposed by Fu and Li. A new method of constructing critical values for these tests is described. Simulations indicate that Tajima's test is generally most powerful against the alternative hypotheses of selective sweep, population bottleneck, and population subdivision, among tests within this class. However, even Tajima's test can detect a selective sweep or bottleneck only if it has occurred within a specific interval of time in the recent past or population subdivision only when it has persisted for a very long time. For greatest power against the particular alternatives studied here, it is better to sequence more alleles than more sites.

scholarly journals Recombination and the power of statistical tests of neutrality

1999 ◽  
Vol 74 (1) ◽  
pp. 65-79 ◽  
Author(s):  
JEFFREY D. WALL
Keyword(s):  
Balancing Selection ◽  
Statistical Tests ◽  
Neutral Theory ◽  
Population Subdivision ◽  
Test Statistics ◽  
Recombination Rates ◽  
Tests Of Neutrality ◽  
Power Studies ◽  
New Statistics ◽  
Population Recombination

Two new test statistics were constructed to detect departures from the equilibrium neutral theory that tend to produce genealogies with longer internal branches (e.g. population subdivision or balancing selection). The new statistics are based on a measure of linkage disequilibrium between adjacent pairs of segregating sites. Simulations were run to determine the power of these and previously proposed test statistics to reject an island model of geographic subdivision. Unlike previous power studies, this one uses a coalescent model with recombination. It is found that recombination rates on the order of the mutation rate substantially reduce the power of most test statistics, and that one of the new test statistics is generally more powerful than the others. Two suggestions are made for increasing the power of the statistical tests examined here. First, they can be made more powerful if critical values are obtained from simulations that condition on a lower bound for the population recombination rate. Secondly, for the same total length sequenced, power is increased if independent loci are considered instead of a single contiguous stretch.

Can statistical tests of neutrality detect selection?

Genetica ◽  
1980 ◽  
Vol 54 (2) ◽  
pp. 185-189 ◽  
Author(s):  
D. L. Hartl ◽  
H. Burla ◽  
H. Jungen
Keyword(s):  
Statistical Tests ◽  
Tests Of Neutrality

scholarly journals DNA Variability and Recombination Rates at X-Linked Loci in Humans

Genetics ◽  
1998 ◽  
Vol 150 (3) ◽  
pp. 1133-1141 ◽  
Author(s):  
Michael W Nachman ◽  
Vanessa L Bauer ◽  
Susan L Crowell ◽  
Charles F Aquadro
Keyword(s):  
Drosophila Melanogaster ◽  
Nucleotide Diversity ◽  
Statistical Tests ◽  
Preliminary Test ◽  
Nucleotide Variation ◽  
Recombination Rates ◽  
Average Value ◽  
Tests Of Neutrality ◽  
Neutral Equilibrium ◽  
Order Of Magnitude

Abstract We sequenced 11,365 bp from introns of seven X-linked genes in 10 humans, one chimpanzee, and one orangutan to (i) provide an average estimate of nucleotide diversity (π) in humans, (ii) investigate whether there is variation in π among loci, (iii) compare ratios of polymorphism to divergence among loci, and (iv) provide a preliminary test of the hypothesis that heterozygosity is positively correlated with the local rate of recombination. The average value for π was low (0.063%, SE = 0.036%), about one order of magnitude smaller than for Drosophila melanogaster, the species for which the best data are available. Among loci, π varied by over one order of magnitude. Statistical tests of neutrality based on ratios of polymorphism to divergence or based on the frequency spectrum of variation within humans failed to reject a neutral, equilibrium model. However, there was a positive correlation between heterozygosity and rate of recombination, suggesting that the joint effects of selection and linkage are important in shaping patterns of nucleotide variation in humans.

scholarly journals Neutrality Tests Using DNA Polymorphism From Multiple Samples

Genetics ◽  
2003 ◽  
Vol 163 (3) ◽  
pp. 1147-1151
Author(s):  
Haipeng Li ◽  
Yunwu Zhang ◽  
Ya-Ping Zhang ◽  
Yun-Xin Fu
Keyword(s):  
Chemokine Receptor ◽  
Dna Polymorphism ◽  
Statistical Tests ◽  
Receptor Gene ◽  
Neutrality Test ◽  
Tests Of Neutrality ◽  
Neutrality Tests ◽  
Polymorphism Data ◽  
Multiple Samples ◽  
Chemokine Receptor Gene

Abstract The polymorphism of a gene or a locus is studied with increasing frequency by multiple laboratories or the same group at different times. Such practice results in polymorphism being revealed by different samples at different regions of the locus. Tests of neutrality have been widely conducted for polymorphism data but commonly used statistical tests cannot be applied directly to such data. This article provides a procedure to conduct a neutrality test and details are given for two commonly used tests. Applying the two new tests to the chemokine-receptor gene (CCR5) in humans, we found that the hypothesis that all mutations are selectively neutral cannot explain the observed pattern of DNA polymorphism.

scholarly journals Genetic hitchhiking versus background selection: the controversy and its implications

2010 ◽  
Vol 365 (1544) ◽  
pp. 1245-1253 ◽  
Author(s):  
Wolfgang Stephan
Keyword(s):  
Population Genetics ◽  
Natural Populations ◽  
Directional Selection ◽  
The Other ◽  
Nucleotide Variation ◽  
Relative Importance ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Genetic Hitchhiking ◽  
Research Activities

The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication.

scholarly journals The Coalescent and Infinite-Site Model of a Small Multigene Family

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 803-810 ◽  
Author(s):  
Hideki Innan
Keyword(s):  
Multigene Family ◽  
Statistical Tests ◽  
Single Copy ◽  
Coalescent Simulation ◽  
Duplicated Genes ◽  
Dna Variation ◽  
Site Model ◽  
Tests Of Neutrality ◽  
Copy Gene ◽  
Infinite Site Model

Abstract The infinite-site model of a small multigene family with two duplicated genes is studied. The expectations of the amounts of nucleotide variation within and between two genes and linkage disequilibrium are obtained, and a coalescent-based method for simulating patterns of polymorphism in a small multigene family is developed. The pattern of DNA variation is much more complicated than that in a single-copy gene, which can be simulated by the standard coalescent. Using the coalescent simulation of duplicated genes, the applicability of statistical tests of neutrality to multigene families is considered.

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