Faculty Opinions recommendation of Slow recovery from inbreeding depression generated by the complex genetic architecture of segregating deleterious mutations.

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

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Lethals in subdivided populations

Genetics Research ◽

10.1017/s0016672305007676 ◽

2005 ◽

Vol 86 (1) ◽

pp. 41-51 ◽

Cited By ~ 13

Author(s):

SYLVAIN GLÉMIN

Keyword(s):

Population Structure ◽

Population Size ◽

Inbreeding Depression ◽

Deleterious Mutations ◽

Mutation Load ◽

General Picture ◽

Analytical Approximations ◽

Size Population ◽

Subdivided Populations ◽

Numerical Approaches

The fate of lethal alleles in populations is of interest in evolutionary and conservation biology for several reasons. For instance, lethals may contribute substantially to inbreeding depression. The frequency of lethal alleles depends on population size, but it is not clear how it is affected by population structure. By analysing the case of the infinite island model by numerical approaches and analytical approximations it is shown that, like population size, population structure affects the fate of lethal alleles if dominance levels are low. Inbreeding depression caused by such alleles is also affected by the population structure, whereas the mutation load is only weakly affected. Heterosis also depends on population structure, but it always remains low, of the order of the mutation rate or less. These patterns are compared with those caused by mildly deleterious mutations to give a general picture of the effect of population structure on inbreeding depression, heterosis, and the mutation load.

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Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter

Genetics Research ◽

10.1017/s0016672399004048 ◽

2000 ◽

Vol 75 (1) ◽

pp. 75-81 ◽

Cited By ~ 120

Author(s):

THOMAS BATAILLON ◽

MARK KIRKPATRICK

Keyword(s):

Population Size ◽

Inbreeding Depression ◽

Deleterious Mutation ◽

Large Population ◽

Genetic Load ◽

Breeding Systems ◽

Deleterious Mutations ◽

Single Locus Analysis ◽

Population Sizes ◽

Inbreeding Rate

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

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Associative overdominance caused by linked detrimental mutations

Genetics Research ◽

10.1017/s0016672300012684 ◽

1971 ◽

Vol 18 (3) ◽

pp. 277-286 ◽

Cited By ~ 127

Author(s):

Tomoko Ohta

Keyword(s):

Blood Group ◽

Inbreeding Depression ◽

Recombination Fraction ◽

Abo Blood Group ◽

Deleterious Mutations ◽

Method Of Moment ◽

Moment Equations ◽

Neutral Locus ◽

Neutral Marker ◽

Image Position

SUMMARYAssociative overdominance due to linked detrimental mutations was investigated using the method of moment equations based on diffusion models. The expectation of the apparent selective value at the marker (neutral) locus has been evaluated. Assume two linked loci, at one of which the steady flux equilibrium is reached under constant mutational input of deleterious mutations (with rate v) having disadvantages hs in heterozygote and s in homozygotes. At another locus, the neutral alleles are segregating with frequencies near 0·5. Let Ne be the effective size of the population and c be the recombination fraction between the two loci. Then the coefficient of associative overdominance at the neutral locus can be obtained by taking the expectation with respect to chromosome frequencies at steady flux equilibrium. It becomes approximatelywhere (LI−L0) is the inbreeding depression caused by deleterious mutations under complete inbreeding, and Nehs ≫ l and hs ≫ v are assumed. More generally, if the inbreeding depression of a chromosome segment with a length of recombination fraction C is (LI−L0) then s′ at the neutral marker at the edge of the segment iswhere hs is the average heterozygote disadvantage of detrimentals.The significance of the associative overdominance is discussed in relation to actual observations. It is proposed that the most of the observed heterozygote superiority including inversion chromosomes of Drosophila, isozyme alleles in Avena and ABO blood group genes in man could be explained by the associated detrimentals.

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Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Heredity ◽

10.1038/s41437-019-0263-6 ◽

2019 ◽

Vol 123 (6) ◽

pp. 709-722 ◽

Cited By ~ 1

Author(s):

Sara Domínguez-García ◽

Carlos García ◽

Humberto Quesada ◽

Armando Caballero

Keyword(s):

Drosophila Melanogaster ◽

Inbreeding Depression ◽

Deleterious Mutations

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GENETIC ARCHITECTURE OF INBREEDING DEPRESSION AND THE MAINTENANCE OF GAMETOPHYTIC SELF-INCOMPATIBILITY

Evolution ◽

10.1111/evo.12495 ◽

2014 ◽

Vol 68 (11) ◽

pp. 3317-3324 ◽

Cited By ~ 17

Author(s):

Camille Gervais ◽

Diala Abu Awad ◽

Denis Roze ◽

Vincent Castric ◽

Sylvain Billiard

Keyword(s):

Inbreeding Depression ◽

Genetic Architecture ◽

Self Incompatibility

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Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal

10.1101/2020.05.27.118877 ◽

2020 ◽

Cited By ~ 3

Author(s):

M.A. Stoffel ◽

S.E. Johnston ◽

J.G. Pilkington ◽

J.M Pemberton

Keyword(s):

Life History ◽

Inbreeding Depression ◽

Genetic Architecture ◽

Rate Variation ◽

Wild Mammal ◽

Annual Survival ◽

Soay Sheep ◽

Genome Wide ◽

A Genome ◽

Recombination Rate Variation

AbstractInbreeding depression is a phenomenon of long-standing importance, but we know surprisingly little about its genetic architecture, precise effects and life-history dynamics in wild populations. Here, we combined 417K imputed SNP genotypes for 5952 wild Soay sheep with detailed long-term life-history data to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH) and these are abundant in Soay sheep, covering on average 24% of the autosomal genome and up to 50% in the most inbred individuals. The ROH landscape is shaped by recombination rate variation and differs widely across the genome, including islands where up to 87% of the population have an ROH and deserts where the ROH prevalence is as low as 4%. We next quantified individual inbreeding as the proportion of the autosomal genome in ROH (FROH) and estimated its effect on annual survival. The consequences of inbreeding are severe; a 10% increase in FROH was associated with a 68% [95% CI 55-78%] decrease in the odds of survival. However, the strength of inbreeding depression is dynamic across the lifespan. We estimate depression to peak in young adults, to decrease into older ages and to be weaker in lambs, where inbreeding effects are possibly buffered by maternal care. Finally, using a genome-wide association scan on ROH, we show that inbreeding causes depression predominantly through many loci with small effects, but we also find three regions in the genome with putatively strongly deleterious mutations. Our study reveals population and genome-wide patterns of homozygosity caused by inbreeding and sheds light on the strength, dynamics and genetic architecture of inbreeding depression in a wild mammal population.

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Fine-scale resolution and analysis of runs of homozygosity in domestic dogs

10.1101/315770 ◽

2018 ◽

Cited By ~ 1

Author(s):

Aaron J. Sams ◽

Adam R. Boyko

Keyword(s):

Inbreeding Depression ◽

Genetic Architecture ◽

Domestic Dogs ◽

Selective Sweeps ◽

Runs Of Homozygosity ◽

Identical By Descent ◽

Density Maps ◽

Genome Wide ◽

Genome Wide Data ◽

Significant Enrichment

Abstract/SummaryInbreeding and consanguinity leave distinct genomic traces, most notably long genomic tracts that are identical by descent and completely homozygous. These runs of homozygosity (ROH) can contribute to inbreeding depression if they contain deleterious variants that are fully or partially recessive. Several lines of evidence have been used to show that long (> 5 megabase (Mb)) ROH are disproportionately likely to harbor deleterious variation, but the extent to which long versus short tracts contribute to autozygosity at loci known to be deleterious and recessive has not been studied.In domestic dogs, nearly 200 mutations are known to cause recessive diseases, most of which can be efficiently assayed using SNP arrays. By examining genome-wide data from over 200,000 markers, including 150 recessive disease variants, we built high-resolution ROH density maps for nearly 2,500 dogs, recording ROH down to 500 kilobases. We observed over 500 homozygous deleterious recessive genotypes in the panel, 90% of which overlapped with ROH inferred by GERMLINE. Although most of these genotypes were contained in ROH over 5 Mb in length, 14% were contained in short (0.5 - 2.5 Mb) tracts, a significant enrichment compared to the genetic background, suggesting that even short tracts are useful for computing inbreeding metrics like the coefficient of inbreeding estimated from ROH (FROH).In our dataset, FROH differed significantly both within and among dog breeds. All breeds harbored some regions of reduced genetic diversity due to drift or selective sweeps, but the degree of inbreeding and the proportion of inbreeding caused by short versus long tracts differed between breeds, reflecting their different population histories. Although only available for a few species, large genome-wide datasets including recessive disease variants hold particular promise not only for disentangling the genetic architecture of inbreeding depression, but also evaluating and improving upon current approaches for detecting ROH.

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Maintenance of High Inbreeding Depression in Selfing Populations: Effects of Coupling of Early- and Late-Acting Mutations

10.1101/748699 ◽

2019 ◽

Cited By ~ 1

Author(s):

Satoki Sakai

Keyword(s):

Simulation Model ◽

Inbreeding Depression ◽

Causal Factor ◽

Deleterious Mutations ◽

Next Generation ◽

Coupling Effects ◽

Plant Populations ◽

Selective Abortion

ABSTRACTHigh estimates of inbreeding depression have been obtained in many plant populations with high selfing rates. However, deleterious mutations might be purged from such populations as a result of selfing. I developed a simulation model assuming the presence of mutations at two sets of loci, namely, early- and late-acting loci, and the selective abortion of embryos coupled with ovule overproduction. In the model, early-acting loci are expressed during embryo initiation, and less vigorous embryos are aborted. Late-acting loci are expressed after selective abortion ends; the surviving embryos (seeds) compete, and some of them form the next generation. If mutations are allowed to occur in both early- and late-acting loci, they increase in frequency in populations with high selfing rates in both sets of loci. However, this phenomenon does not occur if mutations occur in only the early- or late-acting loci. Consistent results are observed even if the total number of loci in which mutations are allowed to occur is the same among simulations with both early- and late-acting loci or only early- or late-acting loci, indicating that the presence of both sets of loci is the causal factor. Thus, the coupling effects of early- and late-acting mutations promote the maintenance of these mutations in populations with high selfing rates.

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