scholarly journals Ancestral Graph with Bias in Gene Conversion

2013 ◽  
Vol 50 (01) ◽  
pp. 239-255 ◽  
Author(s):  
Shuhei Mano
Keyword(s):  
Stochastic Model ◽  
Gene Conversion ◽  
Importance Sampling ◽  
Diffusion Approximation ◽  
Multigene Family ◽  
Dual Process ◽  
Fixation Probability ◽  
Biased Gene Conversion ◽  
Different Types ◽  
Ancestral Graph

Gene conversion is a genetic mechanism by which one gene is ‘copied and pasted’ onto another gene, where the direction can be biased between the different types. In this paper, a stochastic model for biased gene conversion within a d-unlinked multigene family and its diffusion approximation are developed for a finite Moran population. A connection with a d-island model is made. A formula for the fixation probability in the absence of mutation is given. A two-timescale argument is applied in the case of the strong conversion limit. The dual process is generally shown to be a biased voter model, which generates an ancestral bias graph for a given sample. An importance sampling algorithm for computing the likelihood of the sample is deduced.

scholarly journals Ancestral Graph with Bias in Gene Conversion

2013 ◽  
Vol 50 (1) ◽  
pp. 239-255 ◽  
Author(s):  
Shuhei Mano
Keyword(s):  
Stochastic Model ◽  
Gene Conversion ◽  
Importance Sampling ◽  
Diffusion Approximation ◽  
Multigene Family ◽  
Dual Process ◽  
Fixation Probability ◽  
Biased Gene Conversion ◽  
Different Types ◽  
Ancestral Graph

Gene conversion is a genetic mechanism by which one gene is ‘copied and pasted’ onto another gene, where the direction can be biased between the different types. In this paper, a stochastic model for biased gene conversion within a d-unlinked multigene family and its diffusion approximation are developed for a finite Moran population. A connection with a d-island model is made. A formula for the fixation probability in the absence of mutation is given. A two-timescale argument is applied in the case of the strong conversion limit. The dual process is generally shown to be a biased voter model, which generates an ancestral bias graph for a given sample. An importance sampling algorithm for computing the likelihood of the sample is deduced.

scholarly journals INTERCHROMOSOMAL BIASED GENE CONVERSION, MUTATION AND SELECTION IN A MULTIGENE FAMILY

Genetics ◽  
1986 ◽  
Vol 112 (3) ◽  
pp. 681-698
Author(s):  
Montgomery Slatkin
Keyword(s):  
Mathematical Model ◽  
Linkage Disequilibrium ◽  
Gene Conversion ◽  
Multigene Family ◽  
Copy Number ◽  
Relative Fitness ◽  
Mutation Rates ◽  
Biased Gene Conversion ◽  
Mutation And Selection ◽  
Comparable Model

ABSTRACT A mathematical model of the effects of interchromosomal biased gene conversion, mutation and natural selection on a multigene family is developed and analyzed. The model assumes two allelic states at each of n loci. The effects of genetic drift are ignored. The model is developed under the assumption of no recombination, but the analysis shows that, at equilibrium, there is no linkage disequilibrium, which implies that the conclusions are valid for arbitrary recombination among loci. At equilibrium, the balance between mutation, gene conversion and selection depends on the ratio of the mutation rates to the quantity [s + g(2α - 1)/n], where s is the increment or decrement in relative fitness with each additional copy of one of the alleles, g is the conversion rate, and α is a measure of the bias in favor of one of the alleles. When this quantity is large relative to the mutation rates, the allele that has the net advantage, combining the effects of selection and conversion, will be nearly fixed in the multigene family. A comparison of these results with those from a comparable model of intrachromosomal biased conversion shows that biased interchromosomal conversion leads to approximately the same equilibrium copy number as does intrachromosomal conversion of the same strength. Interchromosomal conversion is much more effective in causing the substitution of one allele by another. The relative frequencies of interchromosomal and intrachromosomal conversion is indicated by the extent of the linkage disequilibrium among the loci in a multigene family.

scholarly journals Large scale variation in the rate of de novo mutation, base composition, divergence and diversity in humans

2017 ◽  
Author(s):  
Thomas Smith ◽  
Peter Arndt ◽  
Adam Eyre-Walker
Keyword(s):  
Gene Conversion ◽  
Mutation Rate ◽  
Base Composition ◽  
Large Scale ◽  
De Novo ◽  
Gc Content ◽  
De Novo Mutation ◽  
Biased Gene Conversion ◽  
Different Types ◽  
Scale Variation

AbstractIt has long been suspected that the rate of mutation varies across the human genome at a large scale based on the divergence between humans and other species. It is now possible to directly investigate this question using the large number of de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We show that there is variation in the mutation rate at the 100KB, 1MB and 10MB scale that cannot be explained by variation at smaller scales, however the level of this variation is modest at large scales – at the 1MB scale we infer that ~90% of regions have a mutation rate within 50% of the mean. Different types of mutation show similar levels of variation and appear to vary in concert which suggests the pattern of mutation is relatively constant across the genome and hence unlikely to generate variation in GC-content. We confirm this using two different analyses. We find that genomic features explain less than 50% of the explainable variance in the rate of DNM. As expected the rate of divergence between species and the level of diversity within humans are correlated to the rate of DNM. However, the correlations are weaker than if all the variation in divergence was due to variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. We find no evidence that linked selection affects the relationship between divergence and DNM density. In contrast to divergence, we find that most of the variation in diversity can be explained by variation in the mutation rate. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered.Author summaryUsing a dataset of 40,000 de novo mutations we show that there is large-scale variation in the mutation rate at the 100KB and 1MB scale. We show that different types of mutation vary in concert and in a manner that is not expected to generate variation in base composition; hence mutation bias is not responsible for the large-scale variation in base composition that is observed across human chromosomes. As expected large-scale variation in the rate of divergence between species and the variation within species across the genome, are correlated to the rate of mutation, but the correlation between divergence and the mutation rate is not as strong as they could be. We show that biased gene conversion is responsible for weakening the correlation. In contrast we find that most of the variation across the genome in diversity can be explained by variation in the mutation rate. Finally, we show that the correlation between the rate of mutation in humans and the divergence between humans and other species, weakens as the species become more divergent.

scholarly journals Compromised Function of the Pancreatic Transcription Factor PDX1 in a Lineage of Desert Rodents

2021 ◽  
Author(s):  
Yichen Dai ◽  
Sonia Trigueros ◽  
Peter W. H. Holland
Keyword(s):  
Transcription Factor ◽  
Gene Conversion ◽  
Cell Function ◽  
Protein A ◽  
Gene Promoter ◽  
Homeodomain Protein ◽  
Β Cell ◽  
Desert Rodents ◽  
Biased Gene Conversion ◽  
Β Cell Function

AbstractGerbils are a subfamily of rodents living in arid regions of Asia and Africa. Recent studies have shown that several gerbil species have unusual amino acid changes in the PDX1 protein, a homeodomain transcription factor essential for pancreatic development and β-cell function. These changes were linked to strong GC-bias in the genome that may be caused by GC-biased gene conversion, and it has been hypothesized that this caused accumulation of deleterious changes. Here we use two approaches to examine if the unusual changes are adaptive or deleterious. First, we compare PDX1 protein sequences between 38 rodents to test for association with habitat. We show the PDX1 homeodomain is almost totally conserved in rodents, apart from gerbils, regardless of habitat. Second, we use ectopic gene overexpression and gene editing in cell culture to compare functional properties of PDX1 proteins. We show that the divergent gerbil PDX1 protein inefficiently binds an insulin gene promoter and ineffectively regulates insulin expression in response to high glucose in rat cells. The protein has, however, retained the ability to regulate some other β-cell genes. We suggest that during the evolution of gerbils, the selection-blind process of biased gene conversion pushed fixation of mutations adversely affecting function of a normally conserved homeodomain protein. We argue these changes were not entirely adaptive and may be associated with metabolic disorders in gerbil species on high carbohydrate diets. This unusual pattern of molecular evolution could have had a constraining effect on habitat and diet choice in the gerbil lineage.

Distribution of the number of alleles in multigene families

1992 ◽  
Vol 29 (04) ◽  
pp. 759-769
Author(s):  
R. C. Griffiths
Keyword(s):  
Stochastic Model ◽  
Gene Conversion ◽  
Lower Bounds ◽  
Multigene Families ◽  
Expected Number ◽  
Allele Type ◽  
The Mean

The distribution of the number of alleles in samples from r chromosomes is studied. The stochastic model used includes gene conversion within chromosomes and mutation at loci on the chromosomes. A method is described for simulating the distribution of alleles and an algorithm given for computing lower bounds for the mean number of alleles. A formula is derived for the expected number of samples from r chromosomes which contain the allele type of a locus chosen at random.

Accelerated Evolution of Fetuin-A (FETUA, also AHSG) is Driven by Positive Darwinian Selection, not GC-Biased Gene Conversion

Gene ◽  
2010 ◽  
Vol 463 (1-2) ◽  
pp. 49-55 ◽  
Author(s):  
Yvonne Döring ◽  
Ulrich Zechner ◽  
Christian Roos ◽  
David Rosenkranz ◽  
Hans Zischler ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Positive Darwinian Selection ◽  
Darwinian Selection ◽  
Fetuin A ◽  
Accelerated Evolution ◽  
Biased Gene Conversion

scholarly journals Base composition changes indicate biased gene conversion is a major factor in the evolution of the Fam53A gene

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Andrew David Bergemann ◽  
Joy S. Reidenberg ◽  
Jeffrey T. Laitman ◽  
Lucy Skrabanek ◽  
Isabel Genecin
Keyword(s):  
Gene Conversion ◽  
Base Composition ◽  
Biased Gene Conversion ◽  
Composition Changes

scholarly journals The Red Queen model of recombination hot-spot evolution: a theoretical investigation

2017 ◽  
Vol 372 (1736) ◽  
pp. 20160463 ◽  
Author(s):  
Thibault Latrille ◽  
Laurent Duret ◽  
Nicolas Lartillot
Keyword(s):  
Gene Conversion ◽  
Recombination Rate ◽  
Evolutionary Dynamics ◽  
Genetic Model ◽  
Hot Spot ◽  
Rate Variation ◽  
Red Queen ◽  
Biased Gene Conversion ◽  
Red Queen Model ◽  
The Red Queen

In humans and many other species, recombination events cluster in narrow and short-lived hot spots distributed across the genome, whose location is determined by the Zn-finger protein PRDM9. To explain these fast evolutionary dynamics, an intra-genomic Red Queen model has been proposed, based on the interplay between two antagonistic forces: biased gene conversion, mediated by double-strand breaks, resulting in hot-spot extinction, followed by positive selection favouring new PRDM9 alleles recognizing new sequence motifs. Thus far, however, this Red Queen model has not been formalized as a quantitative population-genetic model, fully accounting for the intricate interplay between biased gene conversion, mutation, selection, demography and genetic diversity at the PRDM9 locus. Here, we explore the population genetics of the Red Queen model of recombination. A Wright–Fisher simulator was implemented, allowing exploration of the behaviour of the model (mean equilibrium recombination rate, diversity at the PRDM9 locus or turnover rate) as a function of the parameters (effective population size, mutation and erosion rates). In a second step, analytical results based on self-consistent mean-field approximations were derived, reproducing the scaling relations observed in the simulations. Empirical fit of the model to current data from the mouse suggests both a high mutation rate at PRDM9 and strong biased gene conversion on its targets. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.

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