The effect of recombination on background selection

SummaryAn approximate equation is derived, which predicts the effect on variability at a neutral locus of background selection due to a set of partly linked deleterious mutations. Random mating, multiplicative fitnesses, and sufficiently large population size that the selected loci are in mutation/selection equilibrium are assumed. Given these assumptions, the equation is valid for an arbitrary genetic map, and for an arbitrary distribution of selection coefficients across loci. Monte Carlo computer simulations show that the formula performs well for small population sizes under a wide range of conditions, and even seems to apply when there are epistatic fitness interactions among the selected loci. Failure occurred only with very weak selection and tight linkage. The formula is shown to imply that weakly selected mutations are more likely than strongly selected mutations to produce regional patterning of variability along a chromosome in response to local variation in recombination rates. Loci at the extreme tip of a chromosome experience a smaller effect of background selection than loci closer to the centre. It is shown that background selection can produce a considerable overall reduction in variation in organisms with small numbers of chromosomes and short maps, such as Drosophila. Large overall effects are less likely in species with higher levels of genetic recombination, such as mammals, although local reductions in regions of reduced recombination might be detectable.

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The effect of deleterious mutations on neutral molecular variation.

Genetics ◽

10.1093/genetics/134.4.1289 ◽

1993 ◽

Vol 134 (4) ◽

pp. 1289-1303 ◽

Cited By ~ 103

Author(s):

B Charlesworth ◽

M T Morgan ◽

D Charlesworth

Keyword(s):

Genetic Recombination ◽

Random Mating ◽

Large Population ◽

Molecular Variation ◽

Background Selection ◽

Deleterious Mutations ◽

Deleterious Alleles ◽

The Mean ◽

Site Diversity ◽

Neutral Mutations

Abstract Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

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Inbreeding depression and genetic load at partially linked loci in a metapopulation

Genetics Research ◽

10.1017/s0016672310000133 ◽

2010 ◽

Vol 92 (2) ◽

pp. 127-140 ◽

Cited By ~ 2

Author(s):

SHU-RONG ZHOU ◽

JOHN R. PANNELL

Keyword(s):

Inbreeding Depression ◽

Random Mating ◽

Genetic Load ◽

Minor Effect ◽

Deleterious Mutations ◽

Recombination Rates ◽

Sexual Systems ◽

Biological Phenomena ◽

Population Turnover ◽

Wide Range

SummaryInbreeding depression has important implications for a wide range of biological phenomena, such as inbreeding avoidance, the evolution and maintenance of sexual systems and extinction rates of small populations. Previous investigations have asked how inbreeding depression evolves in single and subdivided populations through the fixation of deleterious mutations as a result of drift, as well as through the expression of deleterious mutations segregating in a population. These studies have focused on the effects of mutation and selection at single loci, or at unlinked loci. Here, we used simulations to investigate the evolution of genetic load and inbreeding depression due to multiple partially linked loci in metapopulations. Our results indicate that the effect of linkage depends largely on the kinds of deleterious alleles involved. For weakly deleterious and partially recessive mutations, the speed of mutation accumulation at segregating loci in a random-mating subdivided population of a given structure tends to be retarded by increased recombination between adjacent loci – although the highest numbers of fixation of slightly recessive mutant alleles were for low but finite recombination rates. Although linkage had a relatively minor effect on the evolution of metapopulations unless very low values of recombination were assumed, close linkage between adjacent loci tended to enhance population structure and population turnover. Finally, within-deme inbreeding depression, between-deme inbreeding depression and heterosis generally increased with decreased recombination rates. Moreover, increased selfing reduced the effective amount of recombination, and hence the effects of tight linkage on metapopulation genetic structure were decreased with increasing selfing. In contrast, linkage had little effect on the fate of lethal and highly recessive alleles. We compare our simulation results with predictions made by models that ignore the complexities of recombination.

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Effect of Selection Against Deleterious Mutations on the Decline in Heterozygosity at Neutral Loci in Closely Inbreeding Populations

Genetics ◽

10.1093/genetics/153.3.1475 ◽

1999 ◽

Vol 153 (3) ◽

pp. 1475-1489

Author(s):

Jinliang Wang ◽

William G Hill

Keyword(s):

Random Mating ◽

Stochastic Simulations ◽

Type I ◽

Type Ii ◽

Deleterious Mutations ◽

Transition Matrices ◽

Weak Selection ◽

Empirical Estimates ◽

Neutral Locus ◽

Sib Mating

Abstract Transition matrices for selfing and full-sib mating were derived to investigate the effect of selection against deleterious mutations on the process of inbreeding at a linked neutral locus. Selection was allowed to act within lines only (selection type I) or equally within and between lines (type II). For selfing lines under selection type I, inbreeding is always retarded, the retardation being determined by the recombination fraction between the neutral and selected loci and the inbreeding depression from the selected locus, irrespective of the selection coefficient (s) and dominance coefficient (h) of the mutant allele. For selfing under selection type II or full-sib mating under both selection types, inbreeding is delayed by weak selection (small s and sh), due to the associative overdominance created at the neutral locus, and accelerated by strong selection, due to the elevated differential contributions between alternative alleles at the neutral locus within individuals and between lines (for selection type II). For multiple fitness loci under selection, stochastic simulations were run for populations with selfing, full-sib mating, and random mating, using empirical estimates of mutation parameters and inbreeding load in Drosophila. The simulations results are in general compatible with empirical observations.

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The effect of background selection at a single locus on weakly selected, partially linked variants

Genetics Research ◽

10.1017/s0016672399003705 ◽

1999 ◽

Vol 73 (2) ◽

pp. 133-146 ◽

Cited By ~ 23

Author(s):

WOLFGANG STEPHAN ◽

BRIAN CHARLESWORTH ◽

GILEAN McVEAN

Keyword(s):

Sampling Method ◽

Genetic Parameters ◽

Single Locus ◽

Background Selection ◽

Effective Population ◽

Weak Selection ◽

Potential Significance ◽

Neutral Locus ◽

Site Diversity ◽

Rates Of Molecular Evolution

Previous work has shown that genetic diversity at a neutral locus is affected by background selection due to recurrent deleterious mutations as though the effective population size Ne is reduced by a factor that is calculable from genetic parameters such as mutation rates, selection coefficients, and the rates of recombination between sites subject to selection and the neutral locus. Given that silent changes at third coding positions are often subject to weak selection pressures, it is important to develop similar quantitative predictions of the effects of background selection on variation and evolution at weakly selected sites. A diffusion approximation is derived that describes the effects of the presence of a single locus subject to mutation and strongly deleterious selection on variation and evolution at a partially linked, weakly selected locus. The results are validated by computer simulations using the Ito pseudo-sampling method. We show that both nucleotide site diversity and rates of molecular evolution at a weakly selected locus are affected by background selection as though Ne is reduced in the same way as for a neutral locus. Heuristic arguments are presented as to why the change in Ne for the neutral case also applies with weak selection. As in the case of a neutral locus, the number of segregating sites in the population is poorly predicted from the change in Ne. The potential significance of the results in relation to the effects of recombinational environment on molecular variation and evolution is discussed.

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Variable Precision Depth Encoding for 3D Range Geometry Compression

Electronic Imaging ◽

10.2352/issn.2470-1173.2020.17.3dmp-034 ◽

2020 ◽

Vol 2020 (17) ◽

pp. 34-1-34-7

Author(s):

Matthew G. Finley ◽

Tyler Bell

Keyword(s):

Normal Distribution ◽

Arbitrary Distribution ◽

File Size ◽

Geometry Compression ◽

Variable Precision ◽

Wide Range ◽

Novel Method ◽

Encoding Method ◽

Rgb Image ◽

Color Channels

This paper presents a novel method for accurately encoding 3D range geometry within the color channels of a 2D RGB image that allows the encoding frequency—and therefore the encoding precision—to be uniquely determined for each coordinate. The proposed method can thus be used to balance between encoding precision and file size by encoding geometry along a normal distribution; encoding more precisely where the density of data is high and less precisely where the density is low. Alternative distributions may be followed to produce encodings optimized for specific applications. In general, the nature of the proposed encoding method is such that the precision of each point can be freely controlled or derived from an arbitrary distribution, ideally enabling this method for use within a wide range of applications.

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Population fragmentation causes inadequate gene flow and increases extinction risk

10.1093/oso/9780198783398.003.0005 ◽

2017 ◽

Author(s):

Richard Frankham ◽

Jonathan D. Ballou ◽

Katherine Ralls ◽

Mark D. B. Eldridge ◽

Michele R. Dudash ◽

...

Keyword(s):

Gene Flow ◽

Extinction Risk ◽

Random Mating ◽

Large Population ◽

Isolated Population ◽

Population Fragmentation ◽

Single Population ◽

Total Size ◽

Limited Gene Flow

Most species now have fragmented distributions, often with adverse genetic consequences. The genetic impacts of population fragmentation depend critically upon gene flow among fragments and their effective sizes. Fragmentation with cessation of gene flow is highly harmful in the long term, leading to greater inbreeding, increased loss of genetic diversity, decreased likelihood of evolutionary adaptation and elevated extinction risk, when compared to a single population of the same total size. The consequences of fragmentation with limited gene flow typically lie between those for a large population with random mating and isolated population fragments with no gene flow.

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Planetary Nebulae in M31: Abundances, and comparison with bright Planetary Nebulae in the LMC

Symposium - International Astronomical Union ◽

10.1017/s007418090013178x ◽

1997 ◽

Vol 180 ◽

pp. 475-476

Author(s):

M. G. Richer ◽

G. Stasińska ◽

M. L. McCall

Keyword(s):

Planetary Nebula ◽

Luminosity Function ◽

Large Population ◽

Wavelength Region ◽

Planetary Nebulae ◽

Surprising Result ◽

Population Synthesis ◽

Abundance Distribution ◽

Wide Range ◽

The Mean

We have obtained spectra of 28 planetary nebulae in the bulge of M31 using the MOS spectrograph at the Canada-France-Hawaii Telescope. Typically, we observed the [O II] λ3727 to He I λ5876 wavelength region at a resolution of approximately 1.6 å/pixel. For 19 of the 21 planetary nebulae whose [OIII]λ5007 luminosities are within 1 mag of the peak of the planetary nebula luminosity function, our oxygen abundances are based upon a measured [OIII]λ4363 intensity, so they are based upon a measured electron temperature. The oxygen abundances cover a wide range, 7.85 dex < 12 + log(O/H) < 9.09 dex, but the mean abundance is surprisingly low, 12 + log(O/H)–8.64 ± 0.32 dex, i.e., roughly half the solar value (Anders & Grevesse 1989). The distribution of oxygen abundances is shown in Figure 1, where the ordinate indicates the number of planetary nebulae with abundances within ±0.1 dex of any point on the x-axis. The dashed line indicates the mean abundance, and the dotted lines indicate the ±1 σ points. The shape of this abundance distribution seems to indicate that the bulge of M31 does not contain a large population of bright, oxygen-rich planetary nebulae. This is a surprising result, for various population synthesis studies (e.g., Bica et al. 1990) have found a mean stellar metallicity approximately 0.2 dex above solar. This 0.5 dex discrepancy leads one to question whether the mean stellar metallicity is as high as the population synthesis results indicate or if such metal-rich stars produce bright planetary nebulae at all. This could be a clue concerning the mechanism responsible for the variation in the number of bright planetary nebulae observed per unit luminosity in different galaxies (e.g., Hui et al. 1993).

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Microsatellite and Chromosome Evolution of Parthenogenetic Sitobion Aphids in Australia

Genetics ◽

10.1093/genetics/144.2.747 ◽

1996 ◽

Vol 144 (2) ◽

pp. 747-756 ◽

Cited By ~ 4

Author(s):

Paul Sunnucks ◽

Phillip R England ◽

Andrea C Taylor ◽

Dinah F Hales

Keyword(s):

Sexual Reproduction ◽

Chromosome Evolution ◽

Genetic Recombination ◽

Allelic Variation ◽

Repeat Unit ◽

Chromosomal Evolution ◽

Microsatellite Variation ◽

Wide Range ◽

Sexual Recombination ◽

Minimum Numbers

Abstract Single-locus microsatellite variation correlated perfectly with chromosome number in Sitobion miscanthi aphids. The microsatellites were highly heterozygous, with up to 10 alleles per locus in this species. Despite this considerable allelic variation, only seven different S. miscanthi genotypes were discovered in 555 individuals collected from a wide range of locations, hosts and sampling periods. Relatedness between genotypes suggests only two successful colonizations of Australia. There was no evidence for genetic recombination in 555 S. miscanthi so the occurrence of recent sexual reproduction must be near zero. Thus diversification is by mutation and chromosomal rearrangement alone. Since the aphids showed no sexual recombination, microsatellites can mutate without meiosis. Five of seven microsatellite differences were a single repeat unit, and one larger jump is likely. The minimum numbers of changes between karyotypes corresponded roughly one-to-one with microsatellite allele changes, which suggests very rapid chromosomal evolution. A chromosomal fission occurred in a cultured line, and a previously unknown chromosomal race was detected. All 121 diverse S. near fragariae were heterozygous but revealed only one genotype. This species too must have a low rate of sexual reproduction and few colonizations of Australia.

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Inferring Linkage Disequilibrium Between a Polymorphic Marker Locus and a Trait Locus in Natural Populations

Genetics ◽

10.1093/genetics/156.1.457 ◽

2000 ◽

Vol 156 (1) ◽

pp. 457-467 ◽

Cited By ~ 1

Author(s):

Z W Luo ◽

S H Tao ◽

Z-B Zeng

Keyword(s):

Linkage Disequilibrium ◽

Allele Frequency ◽

Random Mating ◽

Natural Populations ◽

Polymorphic Marker ◽

Marker Locus ◽

Model Parameters ◽

Phenotypic Variance ◽

Wide Range ◽

Trait Locus

Abstract Three approaches are proposed in this study for detecting or estimating linkage disequilibrium between a polymorphic marker locus and a locus affecting quantitative genetic variation using the sample from random mating populations. It is shown that the disequilibrium over a wide range of circumstances may be detected with a power of 80% by using phenotypic records and marker genotypes of a few hundred individuals. Comparison of ANOVA and regression methods in this article to the transmission disequilibrium test (TDT) shows that, given the genetic variance explained by the trait locus, the power of TDT depends on the trait allele frequency, whereas the power of ANOVA and regression analyses is relatively independent from the allelic frequency. The TDT method is more powerful when the trait allele frequency is low, but much less powerful when it is high. The likelihood analysis provides reliable estimation of the model parameters when the QTL variance is at least 10% of the phenotypic variance and the sample size of a few hundred is used. Potential use of these estimates in mapping the trait locus is also discussed.

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Microsatellite Variation and Recombination Rate in the Human Genome

Genetics ◽

10.1093/genetics/156.3.1285 ◽

2000 ◽

Vol 156 (3) ◽

pp. 1285-1298 ◽

Cited By ~ 3

Author(s):

Bret A Payseur ◽

Michael W Nachman

Keyword(s):

Recombination Rate ◽

Microsatellite Polymorphism ◽

Published Data ◽

Strong Positive Correlation ◽

Background Selection ◽

Recombination Rates ◽

Microsatellite Variation ◽

Positive Correlation ◽

Genome Recombination ◽

Neutral Mutations

Abstract Background (purifying) selection on deleterious mutations is expected to remove linked neutral mutations from a population, resulting in a positive correlation between recombination rate and levels of neutral genetic variation, even for markers with high mutation rates. We tested this prediction of the background selection model by comparing recombination rate and levels of microsatellite polymorphism in humans. Published data for 28 unrelated Europeans were used to estimate microsatellite polymorphism (number of alleles, heterozygosity, and variance in allele size) for loci throughout the genome. Recombination rates were estimated from comparisons of genetic and physical maps. First, we analyzed 61 loci from chromosome 22, using the complete sequence of this chromosome to provide exact physical locations. These 61 microsatellites showed no correlation between levels of variation and recombination rate. We then used radiation-hybrid and cytogenetic maps to calculate recombination rates throughout the genome. Recombination rates varied by more than one order of magnitude, and most chromosomes showed significant suppression of recombination near the centromere. Genome-wide analyses provided no evidence for a strong positive correlation between recombination rate and polymorphism, although analyses of loci with at least 20 repeats suggested a weak positive correlation. Comparisons of microsatellites in lowest-recombination and highest-recombination regions also revealed no difference in levels of polymorphism. Together, these results indicate that background selection is not a major determinant of microsatellite variation in humans.

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