共查询到20条相似文献,搜索用时 31 毫秒
1.
Effects of Mutation on Selection Limits in Finite Populations with Multiple Alleles 总被引:2,自引:2,他引:0
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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. 相似文献
2.
A general model to explore complex dominance patterns in plant sporophytic self-incompatibility systems
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We developed a general model of sporophytic self-incompatibility under negative frequency-dependent selection allowing complex patterns of dominance among alleles. We used this model deterministically to investigate the effects on equilibrium allelic frequencies of the number of dominance classes, the number of alleles per dominance class, the asymmetry in dominance expression between pollen and pistil, and whether selection acts on male fitness only or both on male and on female fitnesses. We show that the so-called "recessive effect" occurs under a wide variety of situations. We found emerging properties of finite population models with several alleles per dominance class such as that higher numbers of alleles are maintained in more dominant classes and that the number of dominance classes can evolve. We also investigated the occurrence of homozygous genotypes and found that substantial proportions of those can occur for the most recessive alleles. We used the model for two species with complex dominance patterns to test whether allelic frequencies in natural populations are in agreement with the distribution predicted by our model. We suggest that the model can be used to test explicitly for additional, allele-specific, selective forces. 相似文献
3.
Consuegra S Megens HJ Schaschl H Leon K Stet RJ Jordan WC 《Molecular biology and evolution》2005,22(4):1095-1106
We compared major histocompatibility class I allelic diversity in two currently reproductively isolated Atlantic salmon (Salmo salar) populations (Irish and Norwegian) with a common postglacial origin in order to test for among-population differences in allelic composition and patterns of recombination and point mutation. We also examined the evidence for adaptive molecular divergence at this locus by analyzing the rate of amino acid replacement in relation to a neutral expectation. Contrary to our prediction, and in contrast to the situation for other genetic markers, the two populations have almost nonoverlapping sets of major histocompatibility class I alleles. Although there is a strong signal of point mutation that predates population divergence, recent recombination, acting in similar, but not identical, ways in both populations appears to be a significant force in creating new alleles. Moreover, selection acting on peptide-binding residues seems to favor new recombinant alleles and is likely to be responsible for the rapid divergence between populations. 相似文献
4.
Mutation rate in the hypervariable VNTR g3 (D7S22) is affected by allele length and a flanking DNA sequence polymorphism near the repeat array. 总被引:2,自引:1,他引:2
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The hypervariable human minisatellite locus D7S22 (g3) is highly polymorphic. The allelic distribution in D7S22 features a size clustering of the alleles and a comparably low allelic diversity among small alleles. This reduced diversity could reflect a situation where some alleles are less likely to mutate than others. Several factors could explain such an effect, including allele size, variation in repeat composition, and allelic differences in nearby cis-acting elements affecting the mutation rate. We have characterized 40 de novo mutations found on Southern blots in a large amount of paternity-testing material. There is a significant excess of paternal mutations, and small size changes are most frequent. Mutation rate is affected by allele length, with highest rates in larger alleles. Alleles of the family groups with D7S22 mutations and 50 small alleles were analyzed by nucleotide sequencing. Two hundred thirty-six base pairs of the immediate flanking region upstream of the repeat array were PCR amplified and screened for point mutations by DNA sequencing of the PCR products. Two base substitution polymorphisms were identified: one C/G transversion and one A/G transition, 54 bp and 173 bp upstream of the repeat array, respectively. There is a significant association between mutation and occurrence of 54C, while association is not obvious between mutation rate and the 173A/G variants. There is a marked association between different flanking haplotypes and allele size, and within the smallest allele-size group, all alleles had the 54G/173A haplotype. Both allele size and allelic state at site 54 remain associated with mutation rate when the other factor is controlled. Possible mechanisms behind the variation in mutation rate in D7S22 are discussed. 相似文献
5.
Patterns of instability of expanded CAG repeats at the ERDA1 locus in general populations.
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R Deka S Guangyun J Wiest D Smelser S Chunhua Y Zhong R Chakraborty 《American journal of human genetics》1999,65(1):192-198
A highly polymorphic CAG repeat locus, ERDA1, was recently described on human chromosome 17q21.3, with alleles as large as 50-90 repeats and without any disease association in the general population. We have studied allelic distribution at this locus in five human populations and have characterized the mutational patterns by direct observation of 731 meioses. The data show that large alleles (>/=40 CAG repeats) are generally most common in Asian populations, less common in populations of European ancestry, and least common among Africans. We have observed a high intergenerational instability (46. 3%+/-5.1%) of the large alleles. Although the mutation rate is not dependent on parental sex, paternal transmissions have predominantly resulted in contractions, whereas maternal transmissions have yielded expansions. Within this class of large alleles, the mutation rate increases concomitantly with increasing allele size, but the magnitude of repeat size change does not depend on the size of the progenitor allele. Sequencing of specific alleles reveals that the intermediate-sized alleles (30-40 repeats) have CAT/CAC interruptions within the CAG-repeat array. These results indicate that expansion and instability of trinucleotide repeats are not exclusively disease-associated phenomena. The implications of the existence of massively expanded alleles in the general populations are not yet understood. 相似文献
6.
Montgomery Slatkin 《Genetics》1986,112(3):681-698
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. 相似文献
7.
Nitchakarn Noranate Franck Prugnolle Hélène Jouin Adama Tall Laurence Marrama Cheikh Sokhna Marie-Thérèse Ekala Micheline Guillotte Emmanuel Bischoff Christiane Bouchier Jintana Patarapotikul Jun Ohashi Jean-François Trape Christophe Rogier Odile Mercereau-Puijalon 《BMC microbiology》2009,9(1):1-25
Background
Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial.Results
Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles.Conclusion
The Pfmsp1 block2 locus presents a very large population sequence diversity. The lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. The locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. There is no evidence of positive selection for intra-family sequence diversity, consistent with the observed characteristics of the antibody response. 相似文献8.
Genealogical Structure among Alleles Regulating Self-Incompatibility in Natural Populations of Flowering Plants 总被引:5,自引:4,他引:1
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M. K. Uyenoyama 《Genetics》1997,147(3):1389-1400
A method is proposed for characterizing the structure of genealogies among alleles that regulate selfincompatibility in flowering plants. Expected distributions of ratios of divergence times among alleles, scaled by functions of allele number, were generated by numerical simulation. These distributions appeared relatively insensitive to the particular parameter values assigned in the simulations over a fourfold range in effective population size and a 100-fold range in mutation rate. Generalized leastsquares estimates of the scaled indices were obtained from genealogies reconstructed from nucleotide sequences of self-incompatibility alleles from natural populations of two solanaceous species. Comparison of the observed indices to the expected distributions generated by numerical simulation indicated that the allelic genealogy of one species appeared consistent with the symmetric balancing selection generated by self-incompatibility. However, the allelic genealogy of the second species showed unusually long terminal branches, suggesting the operation of additional evolutionary processes. 相似文献
9.
Carlos Castillo-Chavez Simon A. Levin Fred Gould 《Evolution; international journal of organic evolution》1988,42(5):986-994
We develop a mathematical model to explore the evolution of habitat selection and physiological adaptation in a heterogeneous environment. The model assumes the following conditions: 1) a panmictic population of infinite size; 2) prereproductive individuals mobile enough to move between patches; 3) alleles at one locus code for absence or presence of adaptation to detrimental patches; 4) alleles at a second locus code for absence or presence of behavior(s) that cause avoidance of the detrimental patches; 5) additive effects of alleles controlling physiology and behavior; 6) frequency-independent fitness. Results of the model indicate that nontrivial, polymorphic equilibria do not exist. The pattern of genotypic fitnesses and the initial allelic frequencies can influence whether the population adapts by physiological or behavioral mechanisms, or by both. Linkage between the two loci can alter the outcome of evolution, given specified genotypic fitness values and initial allelic frequencies. 相似文献
10.
Changes in gene and genotypic frequencies at four esterase loci were monitored over 25 generations in Composite Cross V, an experimental population of barley, to obtain experimental evidence concerning the balance of forces responsible for: (1) the marked differences in allelic frequencies among barleys from different ecogeographical regions of the world; and (2) the extensive allelic variation found within local populations of barley. Analyses of the highly significant changes in allelic frequencies which occurred in CCV showed they were due to directional selection favoring particular alleles and not to mutation, migration or genetic drift. The results show that intense balancing selection, featuring consistent excesses of heterozygotes, also occurred in CCV. It is concluded that among the factors of neo-Darwinian evolution, natural selection plays the predominant role in determining the observed patterns of allelic variation in the barley species as a whole. 相似文献
11.
Molecular evolution at Mhc genes in two populations of chinook salmon Oncorhynchus tshawytscha 总被引:4,自引:0,他引:4
The DNA sequences of four exons of the MHC (major histocompatibilty complex) were examined in chinook salmon ( Oncorhynchus tshawytscha ) from an interior (Nechako River) and a coastal (Harrison River) population in the Fraser River drainage of British Columbia. Mhc class I A1, A2 and A3 sequences and a class II B1 sequence were obtained by PCR from each of 16–20 salmon from each population. The class I A1 and a pair of linked A2–A3 exons were derived from two different classical salmonid class I genes, Sasa-A and Onmy-UA , respectively. Allelic variation for B1, A1 and A2 was characterized by the high levels of nonsynonymous substitution indicative of the effects of natural selection on Mhc domains that contain peptide binding regions. The number of alleles detected at each of the four exons ranged from three ( B1 ) to 22 ( A1 ), but levels of nucleotide sequence divergence at all four exons were low relative to classical mammalian Mhc genes. The nucleotide similarity among alleles ranged between 89 and 99% over all exons, and all four domains possessed only two major sequence motifs. Allelic distributions at B1, A1 and A3 confirmed the genetic distinctiveness of the Harrison and Nechako chinook salmon populations revealed in previous studies. The two major allelic motifs of B1 and A1 segregated strongly between the populations. In spite of evidence that allelic diversity at these chinook salmon Mhc exons has been generated by selection, the level and distribution of diversity in the two salmon populations strongly reflected the demographic history of the species, which has been characterized by repeated bottlenecks and isolation-by-distance in glacial refugia. 相似文献
12.
Within-population variation at the DNA level will rarely be studied by sequencing of loci of randomly chosen individuals. Instead, individuals will usually be chosen for sequencing based on some knowledge of their genotype. Data collected in this way require new sampling theory. Motivated by these observations, we have examined the sampling properties of a finite population model with two mutation processes and with no selection or recombination. One mutation process generates new alleles according to an infinite-alleles model, and the other generates polymorphisms at sites according to an infinite-sites model. A sample of n genes is considered. The stationary distribution of the number of segregating sites in a subsample from one of the allelic classes in the sample conditional on the allelic configuration of the sample is studied. A recursive scheme is developed to compute the moments of this distribution, and it is shown that the distribution is functionally independent of the number of additional alleles in the sample and their respective frequencies in the sample. For the case in which the sample contains only two alleles, the distribution of the number of segregating sites in a subsample containing both alleles conditional on the sample frequencies of the alleles is studied. The results are applied to the analysis of DNA sequences of two alleles found at the Adh locus of Drosophila melanogaster. No significant departure from the neutral model is detected. 相似文献
13.
In the African clawed frog (Xenopus laevis), two deeply divergent allelic lineages of multiple genes of the class I MHC region have been discovered. For the MHC class I UAA locus, functional differences and the molecular basis for lineages maintenance are unknown. Alleles of linked class I region genes also exhibit strong disequilibrium with specific MHC alleles, but the underlying cause is not clear. We use MHC class Ia sequence data to estimate substitution rates and investigate structural differences between allelic lineages from protein models. Results indicate the operation of natural selection, and differences in the steric properties in the F pocket of the peptide-binding region among lineages. Variability in this pocket likely enables allelic lineages to bind very different sets of peptides and to interact differently with MHC chaperones in the endoplasmic reticulum. These results constitute evidence of the molecular evolutionary basis for 1) the maintenance of allelic lineages, 2) functional differences among lineages, and 3) strong linkage disequilibrium of allelic variants of class I region genes in X. laevis.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
14.
The genes of the major histocompatibility complex (MHC) are a central component of the immune system in vertebrates and have become important markers of functional, fitness-related genetic variation. We have investigated the evolutionary processes that generate diversity at MHC class I genes in a large population of an archaic reptile species, the tuatara (Sphenodon punctatus), found on Stephens Island, Cook Strait, New Zealand. We identified at least 2 highly polymorphic (UA type) loci and one locus (UZ) exhibiting low polymorphism. The UZ locus is characterized by low nucleotide diversity and weak balancing selection and may be either a nonclassical class I gene or a pseudogene. In contrast, the UA-type alleles have high nucleotide diversity and show evidence of balancing selection at putative peptide-binding sites. Twenty-one different UA-type genotypes were identified among 26 individuals, suggesting that the Stephens Island population has high levels of MHC class I variation. UA-type allelic diversity is generated by a mixture of point mutation and gene conversion. As has been found in birds and fish, gene conversion obscures the genealogical relationships among alleles and prevents the assignment of alleles to loci. Our results suggest that the molecular mechanisms that underpin MHC evolution in nonmammals make locus-specific amplification impossible in some species. 相似文献
15.
A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large-scale recombination events (involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small-scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus. 相似文献
16.
Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis 总被引:55,自引:0,他引:55
Variation in internal minisatellite structure can be analyzed by mapping variant repeat units within amplified alleles. A system capable of distinguishing greater than 10(70) allelic states at the human hypervariable locus D1S8 has been developed. Population surveys of internal allelic structure indicate that D1S8 alleles evolve rapidly along haploid chromosome lineages. Internal mapping of deletion mutant alleles physically selected from genomic DNA provides further evidence that germline and somatic mutations altering the number of allelic repeat units seldom if ever arise by unequal exchange between alleles. The existence of low level germline mosaicism for new mutants further indicates that many germline mutation events are premeiotic. Physical selection of new mutants also allows minisatellite mutation rates to be estimated directly in human DNA. 相似文献
17.
Major Histocompatibility Complex (MHC) genes code for proteins involved in the incitation of the adaptive immune response in vertebrates, which is achieved through binding oligopeptides (antigens) of pathogenic origin. Across vertebrate species, substitutions of amino acids at sites responsible for the specificity of antigen binding (ABS) are positively selected. This is attributed to pathogen-driven balancing selection, which is also thought to maintain the high polymorphism of MHC genes, and to cause the sharing of allelic lineages between species. However, the nature of this selection remains controversial. We used individual-based computer simulations to investigate the roles of two phenomena capable of maintaining MHC polymorphism: heterozygote advantage and host-pathogen arms race (Red Queen process). Our simulations revealed that levels of MHC polymorphism were high and driven mostly by the Red Queen process at a high pathogen mutation rate, but were low and driven mostly by heterozygote advantage when the pathogen mutation rate was low. We found that novel mutations at ABSs are strongly favored by the Red Queen process, but not by heterozygote advantage, regardless of the pathogen mutation rate. However, while the strong advantage of novel alleles increased the allele turnover rate, under a high pathogen mutation rate, allelic lineages persisted for a comparable length of time under Red Queen and under heterozygote advantage. Thus, when pathogens evolve quickly, the Red Queen is capable of explaining both positive selection and long coalescence times, but the tension between the novel allele advantage and persistence of alleles deserves further investigation. 相似文献
18.
Slatkin M 《Genetics》2000,154(3):1367-1378
19.
Positive selection and interallelic recombination at the merozoite surface antigen-1 (MSA-1) locus of Plasmodium falciparum. 总被引:1,自引:0,他引:1
A L Hughes 《Molecular biology and evolution》1992,9(3):381-393
DNA sequences of alleles at the merozoite surface antigen-1 (MSA-1) gene locus of the malaria parasite Plasmodium falciparum show evidence of repeated past recombination events between alleles. These include both (1) nonreciprocal recombination events that have homogenized certain gene regions among alleles and (2) reciprocal recombination events that have combined allelic segments with divergent evolutionary histories, thereby enhancing allelic diversity. In three different gene regions, the rate of nonsynonymous nucleotide substitution significantly exceeds that of synonymous nucleotide substitution, implying that positive Darwinian selection has acted to diversify alleles at the amino acid level. The MSA-1 polymorphism seems to be quite ancient; the two major allelic types have been maintained for approximately 35 Myr. 相似文献
20.
Weinig C Dorn LA Kane NC German ZM Halldorsdottir SS Ungerer MC Toyonaga Y Mackay TF Purugganan MD Schmitt J 《Genetics》2003,165(1):321-329
Genetic variation for quantitative traits is often greater than that expected to be maintained by mutation in the face of purifying natural selection. One possible explanation for this observed variation is the action of heterogeneous natural selection in the wild. Here we report that selection on quantitative trait loci (QTL) for fitness traits in the model plant species Arabidopsis thaliana differs among natural ecological settings and genetic backgrounds. At one QTL, the allele that enhanced the viability of fall-germinating seedlings in North Carolina reduced the fecundity of spring-germinating seedlings in Rhode Island. Several other QTL experienced strong directional selection, but only in one site and seasonal cohort. Thus, different loci were exposed to selection in different natural environments. Selection on allelic variation also depended upon the genetic background. The allelic fitness effects of two QTL reversed direction depending on the genotype at the other locus. Moreover, alternative alleles at each of these loci caused reversals in the allelic fitness effects of a QTL closely linked to TFL1, a candidate developmental gene displaying nucleotide sequence polymorphism consistent with balancing selection. Thus, both environmental heterogeneity and epistatic selection may maintain genetic variation for fitness in wild plant species. 相似文献