Differentiation among populations with migration, mutation, and drift: implications for genetic inference

Populations may become differentiated from one another as a result of genetic drift. The amounts and patterns of differentiation at neutral loci are determined by local population sizes, migration rates among populations, and mutation rates. We provide exact analytical expressions for the mean, variance, and covariance of a stochastic model for hierarchically structured populations subject to migration, mutation, and drift. In addition to the expected correlation in allele frequencies among populations in the same geographic region, we demonstrate that there is a substantial correlation in allele frequencies among regions at the top level of the hierarchy. We propose a hierarchical Bayesian model for inference of Wright's F-statistics in a two-level hierarchy in which we estimate the among-region correlation in allele frequencies by substituting replication across loci for replication across time. We illustrate the approach through an analysis of human microsatellite data, and we show that approaches ignoring the among-region correlation in allele frequencies underestimate the amount of genetic differentiation among major geographic population groups by approximately 30%. Finally, we discuss the implications of these results for the use and interpretation of F-statistics in evolutionary studies.     

Similarity coefficients for molecular markers in studies of genetic relationships between individuals for haploid, diploid, and polyploid species

Determining true genetic dissimilarity between individuals is an important and decisive point for clustering and analysing diversity within and among populations, because different dissimilarity indices may yield conflicting outcomes. We show that there are no acceptable universal approaches to assessing the dissimilarity between individuals with molecular markers. Different measures are relevant to dominant and codominant DNA markers depending on the ploidy of organisms. The Dice coefficient is the suitable measure for haploids with codominant markers and it can be applied directly to (0,1)-vectors representing banding profiles of individuals. None of the common measures, Dice, Jaccard, simple mismatch coefficient (or the squared Euclidean distance), is appropriate for diploids with codominant markers. By transforming multiallelic banding patterns at each locus into the corresponding homozygous or heterozygous states, a new measure of dissimilarity within locus was developed and expanded to assess dissimilarity between multilocus states of two individuals by averaging across all codominant loci tested. There is no rigorous well-founded solution in the case of dominant markers. The simple mismatch coefficient is the most suitable measure of dissimilarity between banding patterns of closely related haploid forms. For distantly related haploid individuals, the Jaccard dissimilarity is recommended. In general, no suitable method for measuring genetic dissimilarity between diploids with dominant markers can be proposed. Banding patterns of diploids with dominant markers and polyploids with codominant markers represent individuals' phenotypes rather than genotypes. All dissimilarity measures proposed and developed herein are metrics.     

Patterns of differentiation in a colour polymorphism and in neutral markers reveal rapid genetic changes in natural damselfly populations

The existence and mode of selection operating on heritable adaptive traits can be inferred by comparing population differentiation in neutral genetic variation between populations (often using F(ST) values) with the corresponding estimates for adaptive traits. Such comparisons indicate if selection acts in a diversifying way between populations, in which case differentiation in selected traits is expected to exceed differentiation in neutral markers [F(ST )(selected) > F(ST )(neutral)], or if negative frequency-dependent selection maintains genetic polymorphisms and pulls populations towards a common stable equilibrium [F(ST) (selected) < F(ST) (neutral)]. Here, we compared F(ST) values for putatively neutral data (obtained using amplified fragment length polymorphism) with estimates of differentiation in morph frequencies in the colour-polymorphic damselfly Ischnura elegans. We found that in the first year (2000), population differentiation in morph frequencies was significantly greater than differentiation in neutral loci, while in 2002 (only 2 years and 2 generations later), population differentiation in morph frequencies had decreased to a level significantly lower than differentiation in neutral loci. Genetic drift as an explanation for population differentiation in morph frequencies could thus be rejected in both years. These results indicate that the type and/or strength of selection on morph frequencies in this system can change substantially between years. We suggest that an approach to a common equilibrium morph frequency across all populations, driven by negative frequency-dependent selection, is the cause of these temporal changes. We conclude that inferences about selection obtained by comparing F(ST) values from neutral and adaptive genetic variation are most useful when spatial and temporal data are available from several populations and time points and when such information is combined with other ecological sources of data.     

The estimation of population differentiation with microsatellite markers

Microsatellite markers are routinely used to investigate the genetic structuring of natural populations. The knowledge of how genetic variation is partitioned among populations may have important implications not only in evolutionary biology and ecology, but also in conservation biology. Hence, reliable estimates of population differentiation are crucial to understand the connectivity among populations and represent important tools to develop conservation strategies. The estimation of differentiation is c from Wright's FST and/or Slatkin's RST, an FST -analogue assuming a stepwise mutation model. Both these statistics have their drawbacks. Furthermore, there is no clear consensus over their relative accuracy. In this review, we first discuss the consequences of different temporal and spatial sampling strategies on differentiation estimation. Then, we move to statistical problems directly associated with the estimation of population structuring itself, with particular emphasis on the effects of high mutation rates and mutation patterns of microsatellite loci. Finally, we discuss the biological interpretation of population structuring estimates.     

Molecular markers reveal differentiation among isolates of Coccidioides immitis from California, Arizona and Texas

Coccidioides immitis causes coccidioidomycosis, a fungal disease of both immunocompromised and otherwise healthy people; it is capable of causing large epidemics and the disease is often refractory to chemotherapy. To quantify the magnitude of population differentiation and estimate levels of gene flow in C. immitis , multilocus genotypes were scored for 20–25 clinical isolates from each of Bakersfield (California), Tucson (Arizona), and San Antonio (Texas). The molecular markers used were PCR products with polymorphic restriction endonuclease sites, found and characterized in a previous study of the Tucson population. The data show very highly significant differences in allele frequencies between all three populations, and suggest very low levels of migration between populations. One isolate in the San Antonio sample was an outlier, showing the California-specific allele at all four of the loci distinguishing the two populations, and subsequent inquiries indicated that the infection had indeed been acquired in California. Thus, genetic information can be used to infer the geographical origin of a fungal infection.     

梯棱羊肚菌全基因组SNP/Indel分析及基于Indel标记的遗传连锁图谱构建

基于梯棱羊肚菌Morchella importuna两个子囊孢子培养物的全基因组测序数据,对全基因组范围内的变异位点进行分析。共鉴定到18 438个变异位点,平均每Mbp的变异位点数量为361个;变异位点以单核苷酸多态性SNP为主,共计17 104个,基因组中SNP的频率为335SNPs/Mbp;Indel多态性位点1 334个,以2-10bp的插入缺失为主;73.4% SNP/Indel位于基因间隔区域,外显子区域共检测到3 042个变异位点,占总数的16.50%;对基因功能产生确定影响的移码突变有1 088个,占5.90%,错义突变916个,占比4.97%;不同Scaffold上的SNP/Indel出现频率不同,SNP频率最大的为Scaffold80,平均每Mbp包含2 856个SNP,频率最低为Scaffold60和Scaffold75,分别为16SNPs/Mbp和30SNPs/Mbp;对≥11bp的Indel变异位点进行标记开发和多态性群体分析,成功开发出75对Indel标记。采用原生质体单细胞分离技术,获得了梯棱羊肚菌M04的两个可亲和的同核体菌株M04P01和M04P40,同时采用来自M04子囊果的58个单孢菌株作为作图群体,初步构建了包含75个Indel标记和1个交配型基因的梯棱羊肚菌遗传连锁图谱,共获得12个连锁群,连锁群总长度273.7cM。     

Clonal erosion and genetic drift in cyclical parthenogens – the interplay between neutral and selective processes

The occurrence of alternating phases of clonal and sexual reproduction may strongly impact the interplay between neutral and selective genetic variation in populations. Using a physiologically structured model of the life history of Daphnia, we investigated to what extent clonal erosion associated with selection during the clonal phase affects the genetic structure as observed by neutral markers. Incorporating conservative levels of quantitative genetic variation at 11 physiological and life history traits induces strong clonal erosion, reducing clonal diversity (CD) near the end of the simulations (1000 days) to a level between 1 and 5, even in habitats with high initial CD (10⁸ clones). This strong clonal erosion caused by selection can result in reduced genetic diversity, significant excess of heterozygotes and significant genetic differentiation between populations as observed by neutral markers. Our results indicate that, especially in relatively small habitats, clonal selection may strongly impact the genetic structure and may contribute to the often observed high level of neutral genetic differentiation among natural populations of cyclical parthenogens.     

Microspatial genetic heterogeneity and gene flow in stray cats (Felis catus L.): a comparison of coat colour and microsatellite loci

We analysed levels of genetic differentiation between nine local urban colonies of stray cats using eight coat colour and nine microsatellite loci. Both types of markers revealed a strong differentiation between colonies (FST = 0.15 and 0.09 for coat colour and microsatellite loci, respectively). Three coat colour loci showed extreme levels of genetic differentiation comparatively to other loci and are strongly suspected to be under divergent selective pressures. Microsatellite loci showed significant heterozygote deficiency within colonies (FIS = 0.14), suggesting that coat colour loci are not appropriate to investigate genetic structure at a fine scale because coat colour allele frequencies are based on Hardy-Weinberg equilibrium. The reported pattern conformed to that predicted from the social structuring of cat colonies: aggressive exclusion of immigrants, inbreeding and very low dispersal rate.     

Comparative studies of quantitative trait and neutral marker divergence: a meta-analysis

Comparative studies of quantitative genetic and neutral marker differentiation have provided means for assessing the relative roles of natural selection and random genetic drift in explaining among-population divergence. This information can be useful for our fundamental understanding of population differentiation, as well as for identifying management units in conservation biology. Here, we provide comprehensive review and meta-analysis of the empirical studies that have compared quantitative genetic (Q(ST)) and neutral marker (F(ST)) differentiation among natural populations. Our analyses confirm the conclusion from previous reviews - based on ca. 100% more data - that the Q(ST) values are on average higher than F(ST) values [mean difference 0.12 (SD 0.27)] suggesting a predominant role for natural selection as a cause of differentiation in quantitative traits. However, although the influence of trait (life history, morphological and behavioural) and marker type (e.g. microsatellites and allozymes) on the variance of the difference between Q(ST) and F(ST) is small, there is much heterogeneity in the data attributable to variation between specific studies and traits. The latter is understandable as there is no reason to expect that natural selection would be acting in similar fashion on all populations and traits (except for fitness itself). We also found evidence to suggest that Q(ST) and F(ST) values across studies are positively correlated, but the significance of this finding remains unclear. We discuss these results in the context of utility of the Q(ST)-F(ST) comparisons as a tool for inferring natural selection, as well as associated methodological and interpretational problems involved with individual and meta-analytic studies.     

No evidence of divergence at neutral genetic markers between the two morphologically different subspecies of the most numerous Arctic seabird

Identifying natural populations that might be considered separate units using morphology, genotype or both is important in understanding the process of speciation and for conservation. We examined the relationships between the only two subspecies of the most numerous Arctic seabird, the Little Auk Alle alle, using both morphological (wing and head‐bill lengths) and genetic data (482 base pairs of the mitochondrial control region and seven nuclear microsatellite loci). We found significant morphological differences between the subspecies, A. a. polaris being significantly larger than the nominate A. a. alle. However, we did not find the subspecies to be differentiated at either mitochondrial DNA or at microsatellite loci. Consequently, one evolutionary significant unit is proposed. The similarity of the two subspecies at neutral genetic markers may be due to contemporary gene flow between populations, as well as large population sizes both in the present and in the past, combined with recent post‐glacial colonization of the Artic.     

基于微卫星标记的印度中部Madhya Pradesh地区疟疾强化控制和非强化控制区的斯氏按蚊基因流和种群遗传结构分析

[目的]斯氏按蚊Anopheles stephensi是亚洲东南部城市人体疟疾的主要媒介,印度12％的疟疾病例由其引起.本实验研究了印度中部Madhya Pradesh地区东北部的疟疾强化控制(EMCP)区和非强化控制(非EMCP)区斯氏按蚊的基因流.在EMCP区,由于采用了各种疟疾防控措施因而疟疾病例首先降低,但是很快回升,说明总的疟疾风险维持稳定.[方法]应用7个微卫星位点,对印度中部Madhya Pradesh地区东北部的4个EMCP区和非EMCP区采集的斯氏按蚊进行基因分型,以分析各种群参数.[结果]发现各标记在所有种群中表现出高度的多态性.在两区间未发现很大的遗传多样性.观察到EMCP区的东部种群(FST=0.0485,RST =0.1112)比非EMCP区的北部种群(FST=0.020,RST =0.0145)具有较高的遗传分化,在EMCP区和非EMCP区之间观察到较高的基因流(12.90,6.16,5.06和2.38).RST的灵敏度高于FST,说明分化可能是由于突变而非遗传漂变引起的.[结论]本研究表明,在EMCP区和非EMCP区内以及EMCP区和非EMCP区之间存在很高的基因流.基因流水平高以及抗虫性的发展似乎是EMCP区和非EMCP区疟疾病例发生增加的重要原因.     

Temporal genetic changes between cohorts in a natural population of a marine fish, Diplodus sargus

Temporal changes at 17 allozyme loci in the Diplodus sargus population of Banyuls sur Mer (Mediterranean Sea, France) were monitored within a single population among ten year‐classes (cohorts) sampled over a 6‐month period. The genetic survey was combined with evaluation of the demographic structure of the population by determining variation of abundance between cohorts. The population showed variation in abundance among cohorts ranging from 16 to 214 individuals. Significant divergences in genetic structure were observed between cohorts (P < 0.0001) despite very low values of F_ST (multilocus F_ST over all cohorts = 0.0018). The heterozygosity of each cohort, as well as the F_IS values, was significantly correlated with the abundance of each cohort, with abundant cohorts showing lower heterozygosity and a significant deficit of heterozygotes (positive F_IS values). Finally, multilocus temporal genetic variance (F_k) computed between successive cohorts was higher in low abundance cohorts. Change of heterozygosity between cohorts, distribution of year‐class genetic structure, and change in the genetic structure within a cohort appear to be affected mostly by the abundance of the cohort and are therefore driven by genetic drift. We propose that the Diplodus sargus cohorts are built up from the mixing of families during the pelagic stage or later during recruitment, and that the decrease in heterozygosity leading to a deficit of heterozygotes is characteristic of a Wahlund effect. Such a Wahlund effect would derive from the mixing of the progeny of families made up of few individuals, but exhibiting high fecundity and high variability of reproductive success. Therefore, although cohorts derived from poor recruitment would only group a few families and would exhibit limited deficit of heterozygotes (higher heterozygosity values), they would lead to high genetic drift and appear more divergent (higher mean temporal genetic variance) than cohorts with high abundance. While not demonstrating directly the family structure of marine populations, our survey provides evidence of highly structured populations. © 2002 The Linnean Society of London, Biological Journal of the Linnean Society, 2002, 76 , 9–20.     

利用RAPD标记分析濒危植物白豆杉种群的遗传结构

以我国特有的濒危裸子植物白豆杉为材料,采用RAPD标记对其分布于浙江、江西、湖南和广西的11个天然种群予以检测,通过贝叶斯法估测了种群的遗传分化程度,并和由其他算法得出的结果进行了比较.求出的θ^B（Hickory）、GST（Nei）及φST（AMOVA）值分别为0.5018、0.5865和0.5436;而经由Shannon指数计算出的种群间遗传多样性所占比例为0.4839,同贝叶斯法估计出的结果最为接近.和其他松杉类植物相比,白豆杉种群间发生了极其显著的遗传分化,这可能是因为：（1）种群长期处于星散分布状态;（2）雌雄异株,而生于林下的雌株经常不能正常受粉;（3）种群取样跨越的地理范围宽广.Mantel检验表明,种群间的遗传分化程度和地理距离之间显著相关（r=0.719,P=0.003）.此外还发现白豆杉的遗传变异水平偏低,推测瓶颈效应和遗传漂变对小种群的作用是造成这一后果的重要因素.对白豆杉种群的保育和管理提出了建议.     

High genetic diversity and population differentiation in Boechera fecunda, a rare relative of Arabidopsis

Conservation of endangered species becomes a critical issue with the increasing rates of extinction. In this study, we use 13 microsatellite loci and 27 single-copy nuclear loci to investigate the population genetics of Boechera fecunda, a rare relative of Arabidopsis thaliana, known from only 21 populations in Montana. We investigated levels of genetic diversity and population structure in comparison to its widespread congener, Boechera stricta, which shares similar life history and mating system. Despite its rarity, B. fecunda had levels of genetic diversity similar to B. stricta for both microsatellites and nucleotide polymorphism. Populations of B. fecunda are highly differentiated, with a majority of genetic diversity existing among populations (F(ST) = 0.57). Differences in molecular diversity and allele frequencies between western and eastern population groups suggest they experienced very different evolutionary histories.     

Extensive spatial genetic structure revealed by AFLP but not SSR molecular markers in the wind-pollinated tree, Fagus sylvatica

Studies of fine-scale spatial genetic structure (SGS) in wind-pollinated trees have shown that SGS is generally weak and extends over relatively short distances (less than 30-40 m) from individual trees. However, recent simulations have shown that detection of SGS is heavily dependent on both the choice of molecular markers and the strategy used to sample the studied population. Published studies may not always have used sufficient markers and/or individuals for the accurate estimation of SGS. To assess the extent of SGS within a population of the wind-pollinated tree Fagus sylvatica, we genotyped 200 trees at six microsatellite or simple sequence repeat (SSR) loci and 250 amplified fragment length polymorphisms (AFLP) and conducted spatial analyses of pairwise kinship coefficients. We re-sampled our data set over individuals and over loci to determine the effect of reducing the sample size and number of loci used for SGS estimation. We found that SGS estimated from AFLP markers extended nearly four times further than has been estimated before using other molecular markers in this species, indicating a persistent effect of restricted gene flow at small spatial scales. However, our SSR-based estimate was in agreement with other published studies. Spatial genetic structure in F. sylvatica and similar wind-pollinated trees may therefore be substantially larger than has been estimated previously. Although 100-150 AFLP loci and 150-200 individuals appear sufficient for adequately estimating SGS in our analysis, 150-200 individuals and six SSR loci may still be too few to provide a good estimation of SGS in this species.     

Identifying the minimum number of microsatellite loci needed to assess population genetic structure: A case study in fly culturing

Small, isolated populations are constantly threatened by loss of genetic diversity due to drift. Such situations are found, for instance, in laboratory culturing. In guarding against diversity loss, monitoring of potential changes in population structure is paramount; this monitoring is most often achieved using microsatellite markers, which can be costly in terms of time and money when many loci are scored in large numbers of individuals. Here, we present a case study reducing the number of microsatellites to the minimum necessary to correctly detect the population structure of two Drosophila nigrosparsa populations. The number of loci was gradually reduced from 11 to 1, using the Allelic Richness (AR) and Private Allelic Richness (PAR) as criteria for locus removal. The effect of each reduction step was evaluated by the number of genetic clusters detectable from the data and by the allocation of individuals to the clusters; in the latter, excluding ambiguous individuals was tested to reduce the rate of incorrect assignments. We demonstrate that more than 95% of the individuals can still be correctly assigned when using eight loci and that the major population structure is still visible when using two highly polymorphic loci. The differences between sorting the loci by AR and PAR were negligible. The method presented here will most efficiently reduce genotyping costs when small sets of loci (“core sets”) for long-time use in large-scale population screenings are compiled.     

The propagation of a cultural or biological trait by neutral genetic drift in a subdivided population

We study fixation probabilities and times as a consequence of neutral genetic drift in subdivided populations, motivated by a model of the cultural evolutionary process of language change that is described by the same mathematics as the biological process. We focus on the growth of fixation times with the number of subpopulations, and variation of fixation probabilities and times with initial distributions of mutants. A general formula for the fixation probability for arbitrary initial condition is derived by extending a duality relation between forwards- and backwards-time properties of the model from a panmictic to a subdivided population. From this we obtain new formulae(formally exact in the limit of extremely weak migration) for the mean fixation time from an arbitrary initial condition for Wright's island model, presenting two cases as examples. For more general models of population subdivision, formulae are introduced for an arbitrary number of mutants that are randomly located, and a single mutant whose position is known. These formulae contain parameters that typically have to be obtained numerically, a procedure we follow for two contrasting clustered models. These data suggest that variation of fixation time with the initial condition is slight, but depends strongly on the nature of subdivision. In particular, we demonstrate conditions under which the fixation time remains finite even in the limit of an infinite number of demes. In many cases-except this last where fixation in a finite time is seen--the time to fixation is shown to be in precise agreement with predictions from formulae for the asymptotic effective population size.     

利用微卫星标记初步分析橘小实蝇4个地理种群的遗传多态性

橘小实蝇Bactrocera dorsalis(Bactrocera)(Hendel)是我国重要的检疫性害虫,对果蔬生产及其国际贸易造成很大影响。作者运用微卫星分子标记技术,用6对微卫星引物对采自我国福建、广东、云南3个地区及邻近国越南橘小实蝇种群间的遗传关系进行了初步分析,结果显示上述4个橘小实蝇地理种群间存在一定的遗传差异,地理隔离是造成这一差异的主要原因。     

Words as alleles: connecting language evolution with Bayesian learners to models of genetic drift

Scientists studying how languages change over time often make an analogy between biological and cultural evolution, with words or grammars behaving like traits subject to natural selection. Recent work has exploited this analogy by using models of biological evolution to explain the properties of languages and other cultural artefacts. However, the mechanisms of biological and cultural evolution are very different: biological traits are passed between generations by genes, while languages and concepts are transmitted through learning. Here we show that these different mechanisms can have the same results, demonstrating that the transmission of frequency distributions over variants of linguistic forms by Bayesian learners is equivalent to the Wright–Fisher model of genetic drift. This simple learning mechanism thus provides a justification for the use of models of genetic drift in studying language evolution. In addition to providing an explicit connection between biological and cultural evolution, this allows us to define a ‘neutral’ model that indicates how languages can change in the absence of selection at the level of linguistic variants. We demonstrate that this neutral model can account for three phenomena: the s-shaped curve of language change, the distribution of word frequencies, and the relationship between word frequencies and extinction rates.     

Amplified Fragment Length Polymorphism (AFLP) as a source of genetic markers for red algae

A recent PCR-based fingerprinting technique, amplified fragment length polymorphism (AFLP), was successfully applied to the red alga Chondrus crispus Stackh. This is apparently the first account to describe the application of AFLP methodology to an alga. Six isolates of C. crispus were analyzed by AFLP. A total of twenty-five primer pairs were screened and six primer pairs were selected for further investigation. Both conservative and variable markers were identified within and between populations; some markers were unique to individuals. As such, AFLP should prove useful as a source of genetic markers in algae for applications as diverse as genome mapping to population genetic investigations. This revised version was published online in June 2006 with corrections to the Cover Date.