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.

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 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.

Natural selection and demography as causes of molecular non-randomness

2019 ◽  
pp. 129-158
Author(s):  
Asher D. Cutter
Keyword(s):  
Natural Selection ◽  
Genome Organization ◽  
Population Genetic ◽  
Genetic Linkage ◽  
Balancing Selection ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Evolutionary Patterns ◽  
Plastid Genomes ◽  
Tests Of Neutrality

Chapter 7, “Natural selection and demography as causes of molecular non-randomness,” outlines the predictable molecular evolutionary patterns that arise when the Neutral Theory has its assumptions violated. It summarizes predictions about genetic variation, the shape of genealogies, and the accumulation of divergence between lineages when natural selection and non-standard demographic scenarios occur in populations. This chapter provides an overview of the general, qualitative impacts on molecular population genetic data by positive selection, purifying selection, and balancing selection, as well as by demographic population growth, contraction, and subdivision. It covers the concepts of selective sweeps, genetic hitchhiking, and background selection, placed in a heuristic context of skews in polymorphism, genealogies, the site frequency spectrum, and distinct metrics of divergence. This chapter also summarizes the consequences of genetic linkage to sex chromosomes and plastid genomes. This overview builds up intuition about selection, demography, and genome organization as important molecular population genetic factors that motivate further analysis with quantitative tests of neutrality.

scholarly journals Statistical Tests of Symbolic Dynamics

Mathematics ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 817
Author(s):  
Fernando López ◽  
Mariano Matilla-García ◽  
Jesús Mur ◽  
Manuel Ruiz Marín
Keyword(s):  
Monte Carlo ◽  
Symbolic Dynamics ◽  
Null Hypothesis ◽  
Statistical Tests ◽  
General Applicability ◽  
Monte Carlo Experiments ◽  
The Mean ◽  
Theoretical Application ◽  
New Statistics ◽  
General Method

A novel general method for constructing nonparametric hypotheses tests based on the field of symbolic analysis is introduced in this paper. Several existing tests based on symbolic entropy that have been used for testing central hypotheses in several branches of science (particularly in economics and statistics) are particular cases of this general approach. This family of symbolic tests uses few assumptions, which increases the general applicability of any symbolic-based test. Additionally, as a theoretical application of this method, we construct and put forward four new statistics to test for the null hypothesis of spatiotemporal independence. There are very few tests in the specialized literature in this regard. The new tests were evaluated with the mean of several Monte Carlo experiments. The results highlight the outstanding performance of the proposed test.

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 Nucleotide Variation at theCHALCONE ISOMERASELocus inArabidopsis thaliana

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 863-872 ◽  
Author(s):  
Helmi Kuittinen ◽  
Montserrat Aguadé
Keyword(s):  
Nucleotide Diversity ◽  
Direct Relationship ◽  
Selective Sweep ◽  
Balancing Selection ◽  
Neutral Theory ◽  
Low Frequency ◽  
The Other ◽  
Nucleotide Variation ◽  
Rapid Population Growth ◽  
History Of

AbstractAn ~1.9-kb region encompassing the CHI gene, which encodes chalcone isomerase, was sequenced in 24 worldwide ecotypes of Arabidopsis thaliana (L.) Heynh. and in 1 ecotype of A. lyrata ssp. petraea. There was no evidence for dimorphism at the CHI region. A minimum of three recombination events was inferred in the history of the sampled ecotypes of the highly selfing A. thaliana. The estimated nucleotide diversity (θTOTAL = 0.004, θSIL = 0.005) was on the lower part of the range of the corresponding estimates for other gene regions. The skewness of the frequency spectrum toward an excess of low-frequency polymorphisms, together with the bell-shaped distribution of pairwise nucleotide differences at CHI, suggests that A. thaliana has recently experienced a rapid population growth. Although this pattern could also be explained by a recent selective sweep at the studied region, results from the other studied loci and from an AFLP survey seem to support the expansion hypothesis. Comparison of silent polymorphism and divergence at the CHI region and at the Adh1 and ChiA revealed in some cases a significant deviation of the direct relationship predicted by the neutral theory, which would be compatible with balancing selection acting at the latter regions.

scholarly journals An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components

2017 ◽  
Author(s):  
Nathaniel P. Sharp ◽  
Aneil F. Agrawal
Keyword(s):  
Genetic Variance ◽  
Balancing Selection ◽  
Statistical Tests ◽  
Balance Model ◽  
Male Mating ◽  
Deleterious Mutations ◽  
Fitness Component ◽  
Fitness Components ◽  
Female Fecundity ◽  
Mutational Variance

ABSTRACTDespite decades of research, the factors that maintain genetic variation for fitness are poorly understood. Mutation selection balance will always contribute to standing variance, but it is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to mutation-selection balance can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the actual standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the mutation-selection balance model, and could be used to identify traits or populations where genetic variance is maintained by factors beyond mutation-selection balance. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. To encourage the application of this approach, we describe the underlying theory and use it to test the mutation selection balance model for three traits in Drosophila melanogaster. We find some evidence for non-mutational variance in male mating success and female fecundity relative to larval viability, which is consistent with balancing selection on sexual fitness components. Finally, we discuss the theoretical and practical limitations to this approach, and discuss how to apply it successfully.

scholarly journals Transition from background selection to associative overdominance promotes diversity in regions of low recombination

2019 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Fanny Pouyet ◽  
Laurent Excoffier ◽  
Stephan Peischl
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Heterozygote Advantage ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Locus Model ◽  
Genome Wide ◽  
Linked Selection

SummaryLinked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

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