scholarly journals Joint inference of demography and mutation rates from polymorphism data and pedigrees

2016 ◽  
Author(s):  
Florence Parat ◽  
Sándor Miklós Szilágyi ◽  
Daniel Wegmann ◽  
Aurélien Tellier
Keyword(s):  
Mutation Rate ◽  
Overlapping Generations ◽  
Genetic Data ◽  
Mutation Rates ◽  
Pedigree Information ◽  
Pedigree Data ◽  
Computationally Efficient ◽  
Effective Population ◽  
Joint Inference ◽  
Major Interest

ABSTRACTInference of demography and mutation rates is of major interest but difficult because genetic data is only informative about the population mutation rate, the product of the effective population size times the mutation rate, and not about these quantities individually. Here we show that this limitation can be overcome by combining genetic data with pedigree information. To successfully use pedigree data, however, important aspects of real populations such as the presence of two sexes, unbalanced sex ratios and overlapping generations have to be taken into account. We present here an extension of the classic Wright-Fisher model accounting for these effects and show that the coalescent process under this model reduces to the classic Kingman coalescent with specific scaling parameters. We further derive the probability of a pedigree under that model and show how pedigree data can thus be used to infer demographic parameters. Finally, we present a computationally efficient inference approach combining pedigree information and genetic data summarized by the site frequency spectrum (SFS) that allows for the joint inference of the mutation rate, sex-specific population sizes and the fraction of overlapping generations. Using simulations we then show that these parameters can be accurately inferred from pedigrees spanning just a few generations, as are available for many species. We finally discuss future possible extensions of the model and inference framework necessary for applications to wild and domesticated species, namely the account for more complex demographies and the uncertainty in assigning pedigree individuals to specific generations.

scholarly journals THE DYNAMICS OF FINITE HAPLOID POPULATIONS WITH OVERLAPPING GENERATIONS. II. THE DIFFUSION APPROXIMATION

Genetics ◽  
1979 ◽  
Vol 92 (1) ◽  
pp. 339-351
Author(s):  
Ted H Emigh
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Diffusion Approximation ◽  
Overlapping Generations ◽  
Mutation Rates ◽  
Reproductive Value ◽  
Selection Coefficient ◽  
Effective Population ◽  
Haploid Population

ABSTRACT The dynamics of a gene in a haploid population can be explained approximately by considering the average reproductive value of the gene. The dynamics of the average reproductive value are similar to those of a gene in a population with nonoverlapping generations with the following modifications: The effective population size, Ne, replaces N; the average mutation rates,μ* and v* replace μ and v; the average overall selection r*+(T-l)s** replaces s; and time is measured in terms of generations, T. The implications of the average selection coefficient to adaptive life histones are discussed.

scholarly journals Genetic Variability in the Italian Heavy Draught Horse from Pedigree Data and Genomic Information

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1310
Author(s):  
Enrico Mancin ◽  
Michela Ablondi ◽  
Roberto Mantovani ◽  
Giuseppe Pigozzi ◽  
Alberto Sabbioni ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Genomic Structure ◽  
Population Level ◽  
Snp Markers ◽  
Pedigree Information ◽  
Pedigree Data ◽  
Selection Signatures ◽  
Effective Population ◽  
Genomic Inbreeding ◽  
Inbreeding Level

This study aimed to investigate the genetic diversity in the Italian Heavy Horse Breed from pedigree and genomic data. Pedigree information for 64,917 individuals were used to assess inbreeding level, effective population size (Ne), and effective numbers of founders and ancestors (fa/fe). Genotypic information from SNP markers were available for 267 individuals of both sexes, and it allowed estimating genomic inbreeding in two methods (observed versus expected homozygosity and from ROH) to study the breed genomic structure and possible selection signatures. Pedigree and genomic inbreeding were greatly correlated (0.65 on average). The inbreeding trend increased over time, apart from periods in which the base population enlarged, when Ne increased also. Recent bottlenecks did not occur in the genome, as fa/fe have shown. The observed homozygosity results were on average lower than expected, which was probably due to the use of French Breton stallions to support the breed genetic variability. High homozygous regions suggested that inbreeding increased in different periods. Two subpopulations were distinguished, which was probably due to the different inclusion of French animals by breeders. Few selection signatures were found at the population level, with possible associations to disease resistance. The almost low inbreeding rate suggested that despite the small breed size, conservation actions are not yet required.

scholarly journals Effects of mutation on selection limits in finite populations with multiple alleles.

Genetics ◽  
1989 ◽  
Vol 122 (4) ◽  
pp. 977-984
Author(s):  
Z B Zeng ◽  
H Tachida ◽  
C C Cockerham
Keyword(s):  
Mutation Rate ◽  
Present Model ◽  
Substantial Effect ◽  
Mutation Rates ◽  
Additive Effects ◽  
Selection Coefficient ◽  
Effective Population ◽  
Weak Selection ◽  
Multiple Alleles ◽  
Selection Limit

Abstract The ultimate response to directional selection (i.e., the selection limit) under recurrent mutation is analyzed by a diffusion approximation for a population in which there are k possible alleles at a locus. The limit mainly depends on two scaled parameters S (= 4Ns sigma a) and theta (= 4Nu) and k, the number of alleles, where N is the effective population size, u is the mutation rate, s is the selection coefficient, and sigma 2a is the variance of allelic effects. When the selection pressure is weak (S less than or equal to 0.5), the limit is given approximately by 2S sigma a[1 - (1 + c2)/k]/(theta + 1) for additive effects of alleles, where c is the coefficient of variation of the mutation rates among alleles. For strong selection, other approximations are devised to analyze the limit in different parameter regions. The effect of mutation on selection limits largely relies on the potential of mutation to introduce new and better alleles into the population. This effect is, however, bounded under the present model. Unequal mutation rates among alleles tend to reduce the selection limit, and can have a substantial effect only for small numbers of alleles and weak selection. The selection limit decreases as the mutation rate increases.

scholarly journals Evolution of mutation rates in hypermutable populations of Escherichia coli propagated at very small effective population size

2017 ◽  
Vol 13 (3) ◽  
pp. 20160849 ◽  
Author(s):  
Tanya Singh ◽  
Meredith Hyun ◽  
Paul Sniegowski
Keyword(s):  
Escherichia Coli ◽  
Genetic Variation ◽  
Mutation Rate ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Ultimate Source ◽  
Systematic Evolution ◽  
Small Effective Size ◽  
Small Effective Population Size

Mutation is the ultimate source of the genetic variation—including variation for mutation rate itself—that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower mutation rates in replicate hypermutable Escherichia coli populations experimentally propagated at very small effective size—a circumstance under which selection is greatly reduced. Several populations went extinct during this experiment, and these populations tended to evolve elevated mutation rates. In contrast, populations that survived to the end of the experiment tended to evolve decreased mutation rates. We discuss the relevance of our results to current ideas about the evolution, maintenance and consequences of high mutation rates.

scholarly journals Evolution of Mutation Rate in Astronomically Large Phytoplankton Populations

2020 ◽  
Vol 12 (7) ◽  
pp. 1051-1059
Author(s):  
Marc Krasovec ◽  
Rosalind E M Rickaby ◽  
Dmitry A Filatov
Keyword(s):  
Genetic Diversity ◽  
Population Size ◽  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Large Population ◽  
Marine Phytoplankton ◽  
Mutation Rates ◽  
Effective Population ◽  
Spontaneous Mutation Rate ◽  
Large Populations

Abstract Genetic diversity is expected to be proportional to population size, yet, there is a well-known, but unexplained lack of genetic diversity in large populations—the “Lewontin’s paradox.” Larger populations are expected to evolve lower mutation rates, which may help to explain this paradox. Here, we test this conjecture by measuring the spontaneous mutation rate in a ubiquitous unicellular marine phytoplankton species Emiliania huxleyi (Haptophyta) that has modest genetic diversity despite an astronomically large population size. Genome sequencing of E. huxleyi mutation accumulation lines revealed 455 mutations, with an unusual GC-biased mutation spectrum. This yielded an estimate of the per site mutation rate µ = 5.55×10−10 (CI 95%: 5.05×10−10 – 6.09×10−10), which corresponds to an effective population size Ne ∼ 2.7×106. Such a modest Ne is surprising for a ubiquitous and abundant species that accounts for up to 10% of global primary productivity in the oceans. Our results indicate that even exceptionally large populations do not evolve mutation rates lower than ∼10−10 per nucleotide per cell division. Consequently, the extreme disparity between modest genetic diversity and astronomically large population size in the plankton species cannot be explained by an unusually low mutation rate.

scholarly journals Genome wide estimates of mutation rates and spectrum in Schizosaccharomyces pombe indicate CpG sites are highly mutagenic despite the absence of DNA methylation

2015 ◽  
Author(s):  
Megan G Behringer ◽  
David W Hall
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Mutation Rate ◽  
Life Histories ◽  
Mutation Rates ◽  
Effective Population ◽  
Additional Mechanism ◽  
Yeast Saccharomyces Cerevisiae ◽  
Ascomycetous Yeast ◽  
Cpg Dinucleotides ◽  
Genome Wide

We accumulated mutations for 1952 generations in 79 initially identical, haploid lines of the fission yeast Schizosaccharomyces pombe and then performed whole-genome sequencing to determine the mutation rates and spectrum. We captured 696 spontaneous mutations across the 79 mutation accumulation lines. We compared the mutation spectrum and rate to another model ascomycetous yeast, the budding yeast Saccharomyces cerevisiae. While the two organisms are approximately 600 million years diverged from each other, they share similar life histories, genome size and genomic G/C content. We found that Sc. pombe and S. cerevisiae have similar mutation rates, contrary to what was expected given Sc. pombe’s smaller reported effective population size. Sc. pombe’s also exhibits a strong insertion bias in comparison to S. cerevisiae,. Intriguingly, we observed an increased mutation rate at cytosine nucleotides, specifically CpG nucleotides, which is also seen in S. cerevisiae. However, the absence of methylation in Sc. pombe and the pattern of mutation at these sites, primarily C→ A as opposed to C→T, strongly suggest that the increased mutation rate is not caused by deamination of methylated cytosines. This result implies that the high mutability of CpG dinucleotides in other species may be caused in part by an additional mechanism than methylation.

scholarly journals A phylogenetic estimator of effective population size or mutation rate.

Genetics ◽  
1994 ◽  
Vol 136 (2) ◽  
pp. 685-692 ◽  
Author(s):  
Y X Fu
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Mutation Rate ◽  
Dna Sequences ◽  
High Efficiency ◽  
Minimum Variance ◽  
Population Subdivision ◽  
Effective Population ◽  
Fisher Model ◽  
Mitochondrial Sequences

Abstract A new estimator of the essential parameter theta = 4Ne mu from DNA polymorphism data is developed under the neutral Wright-Fisher model without recombination and population subdivision, where Ne is the effective population size and mu is the mutation rate per locus per generation. The new estimator has a variance only slightly larger than the minimum variance of all possible unbiased estimators of the parameter and is substantially smaller than that of any existing estimator. The high efficiency of the new estimator is achieved by making full use of phylogenetic information in a sample of DNA sequences from a population. An example of estimating theta by the new method is presented using the mitochondrial sequences from an American Indian population.

Pedigree Data Analysis With Crossover Interference

Genetics ◽  
2003 ◽  
Vol 164 (4) ◽  
pp. 1561-1566
Author(s):  
Sharon Browning
Keyword(s):  
Data Analysis ◽  
Linkage Analysis ◽  
Importance Sampling ◽  
Genetic Data ◽  
Genotype Data ◽  
Pedigree Data ◽  
Chi Square ◽  
Crossover Interference ◽  
Map Construction ◽  
Interference Models

AbstractWe propose a new method for calculating probabilities for pedigree genetic data that incorporates crossover interference using the chi-square models. Applications include relationship inference, genetic map construction, and linkage analysis. The method is based on importance sampling of unobserved inheritance patterns conditional on the observed genotype data and takes advantage of fast algorithms for no-interference models while using reweighting to allow for interference. We show that the method is effective for arbitrarily many markers with small pedigrees.

scholarly journals Mutation rate analysis via parent–progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation

2016 ◽  
Vol 283 (1841) ◽  
pp. 20161785 ◽  
Author(s):  
Long Wang ◽  
Yanchun Zhang ◽  
Chao Qin ◽  
Dacheng Tian ◽  
Sihai Yang ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Recombination Rate ◽  
Mutation Rates ◽  
Recombination Rates ◽  
Rate Analysis ◽  
A Genome ◽  
Break Points ◽  
New Mutations

Mutation rates and recombination rates vary between species and between regions within a genome. What are the determinants of these forms of variation? Prior evidence has suggested that the recombination might be mutagenic with an excess of new mutations in the vicinity of recombination break points. As it is conjectured that domesticated taxa have higher recombination rates than wild ones, we expect domesticated taxa to have raised mutation rates. Here, we use parent–offspring sequencing in domesticated and wild peach to ask (i) whether recombination is mutagenic, and (ii) whether domesticated peach has a higher recombination rate than wild peach. We find no evidence that domesticated peach has an increased recombination rate, nor an increased mutation rate near recombination events. If recombination is mutagenic in this taxa, the effect is too weak to be detected by our analysis. While an absence of recombination-associated mutation might explain an absence of a recombination–heterozygozity correlation in peach, we caution against such an interpretation.

Evolution of mutation rate and virulence among human retroviruses

1994 ◽  
Vol 346 (1317) ◽  
pp. 333-343 ◽  
Keyword(s):  
Immune System ◽  
Mutation Rate ◽  
Hiv Infections ◽  
Molecular Data ◽  
Mutation Rates ◽  
Rapid Progression ◽  
Human T Cell ◽  
Large Numbers ◽  
The Individual ◽  
Multicellular Organisms

High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection, hiv infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVS are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to aids, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the aids pandemic and prevent similar pandemics from arising in the future.

Sign in / Sign up

Export Citation Format

Share Document