Demic structure and its relation with the distribution of an adaptive trait in Danish flea beetles

The flea beetle Phyllotreta nemorum is an oligophagous species using crucifers as host plants. In Denmark two populations have been found which use Barbarea vulgaris ssp. arcuata (G-type) as a host plant, whereas this plant is unsuitable for the survival of the majority of P. nemorum. In the locations in which these two populations occur, alternative host plants are also present. The plants occur in patches, some of which contain a mixture of host plants. In this study of allozyme variation, genetic differentiation between P. nemorum using different host plants in patches in the two different localities was studied hierarchically to assess substructuring of the populations. Evidence was found for low, but significant, amounts of genetic differentiation between (sub)populations using spatially separated plant patches at a distance of approximately 100 m to 1 km (theta = 0.009) and between localities approximately 44 km apart (theta = 0.026), and there was an association between genetic differentiation and geographical distance. No genetic differentiation was found between beetles from different host plants with overlapping local distributions. No evidence was thus found for sympatric host race formation. The geographical distribution of genes enabling P. nemorum to use B. vulgaris as a host plant (100% 'resistant' beetles in samples from B. vulgaris, but much fewer on patches containing only alternative host plants) contrasts with the relatively low amount of genetic differentiation at the neutral allozyme loci. This distribution of 'resistant' beetles (to B. vulgaris defence) is likely to be influenced by local differences in selection and asymmetric gene flow.     

Molecular evidence for selection on female color polymorphism in the damselfly Ischnura graellsii

The significance of female color polymorphism in Odonata remains controversial despite many field studies. The importance of random factors (founder effects, genetic drift and migration) versus selective forces for the maintenance of this polymorphism is still discussed. In this study, we specifically test whether the female color polymorphism of Ischnura graellsii (Odonata, Coenagrionidae) is under selection in the wild. We compared the degree of genetic differentiation based on RAPD markers (assumed to be neutral) with the degree of differentiation based on color alleles. Weir and Cockerham's theta values showed a significant degree of population differentiation for both sets of loci (RAPD and color alleles) but the estimated degree of population differentiation (theta) was significantly greater for the set of RAPD loci. This result shows that some sort of selection contributes to the maintenance of similar color morph frequencies across the studied populations. Our results combined with those of previous field studies suggest that at least in some I. graellsii populations, density-dependent mechanisms might help to prevent the loss of this polymorphism but cannot explain the similarity in morph frequencies among populations.     

The analysis of space use patterns.

In this paper we describe and test a new method for characterizing the space use patterns of individual animals on the basis of successive locations of marked individuals. Existing methods either do not describe space use in probabilistic terms, e.g. the maximum distance between locations or the area of the convex hull of all locations, or they assume a priori knowledge of the probabilistic shape of each individual's use pattern, e.g. bivariate or circular normal distributions. We develop a method for calculating a probability of location distribution for an average individual member of a population that requires no assumptions about the shape of the distribution (we call this distribution the population utilization distribution or PUD). Using nine different sets of location data, we demonstrate that these distributions accurately characterize the space use patterns of the populations from which they were derived. The assumption of normality is found to result in a consistent and significant overestimate of the area of use. We then describe a function which relates probability of location to area (termed the MAP index) which has a number of advantages over existing size indices. Finally, we show how any quantities such as the MAP index derived from our average distributions can be subjected to standard statistical tests of significance.     

Genetic Diversity of Twelve Switchgrass Populations Using Molecular and Morphological Markers

Switchgrass (Panicum virgatum L.) is a warm season, C₄ perennial grass native to most of North America with numerous applications, including use as a bioenergy feedstock species. To date, no studies on genetic diversity in switchgrass have been conducted that use both molecular and morphological markers. The objectives of this study were to assess genetic diversity and determine differences among and between 12 switchgrass populations grown in New Jersey by examining both morphological and molecular characteristics, and to determine whether morphological, molecular, and/or combined data sets can detect ecotype and/or geographical differences at the population level. Twelve plants from each population were characterized with 16 switchgrass expressed sequence tag-simple sequence repeat markers (EST-SSRs) and seven morphological characters. Data was analyzed using GenAlEx and Unweighted Pair-Group Method of Averages (UPGMA) cluster analysis. Most (64%) of the molecular variation in switchgrass populations exists among individuals within populations, with lesser amounts between populations (36%). Upland and lowland populations were distinguished in all three data sets. Some eastern US and midwestern US populations were distinct in all three data sets. Similarities were observed between all three data sets indicating molecular markers may be useful for identifying morphological differences or other adaptive traits. The combined data set was the most useful in differentiating populations based on geography and found separation between midwestern and eastern upland populations. The results indicate that the combination of morphological and molecular markers may be useful in future applications such as genetic diversity studies, plant variety protection, cultivar identification, and/or identifying geographic origin.     

Possible heterogeneity in the phosphoglycolate phosphatase (PGP)-haptoglobin alpha (HPA) linkage.

Previous investigators have reported loose linkage in both sexes for phosphoglycolate phosphatase (PGP) and haptoglobin alpha (HPA). We present results of linkage studies between PGP and HPA in two data sets, one from Houston and the other an update of an earlier report from Los Angeles. Using quadratic interpolation to estimate the male (theta m) and female (theta f) recombination values from bivariate lod tables, we found for the Houston data that theta m = 0.43 and theta f = 0.03 at the maximum lod score of z = 2.23. For the Los Angeles series, we found that theta m = 0.31, theta f = 0.48, and z = 0.27. We invoke heterogeneity in the recombination value in different families as an explanation of our findings. We also recommend that bivariate lod tables should always be generated, even though not reported. This is because the usual assumption of theta m = theta f (and, rarely, theta f = 1.8 theta f) under which lod scores are computed may be invalid in many cases.     

Empirical Bayes procedure for estimating genetic distance between populations and effective population size

We developed an empirical Bayes procedure to estimate genetic distances between populations using allele frequencies. This procedure makes it possible to describe the skewness of the genetic distance while taking full account of the uncertainty of the sample allele frequencies. Dirichlet priors of the allele frequencies are specified, and the posterior distributions of the various composite parameters are obtained by Monte Carlo simulation. To avoid overdependence on subjective priors, we adopt a hierarchical model and estimate hyperparameters by maximizing the joint marginal-likelihood function. Taking advantage of the empirical Bayesian procedure, we extend the method to estimate the effective population size using temporal changes in allele frequencies. The method is applied to data sets on red sea bream, herring, northern pike, and ayu broodstock. It is shown that overdispersion overestimates the genetic distance and underestimates the effective population size, if it is not taken into account during the analysis. The joint marginal-likelihood function also estimates the rate of gene flow into island populations.     

Bayesian inference of recent migration rates using multilocus genotypes

A new Bayesian method that uses individual multilocus genotypes to estimate rates of recent immigration (over the last several generations) among populations is presented. The method also estimates the posterior probability distributions of individual immigrant ancestries, population allele frequencies, population inbreeding coefficients, and other parameters of potential interest. The method is implemented in a computer program that relies on Markov chain Monte Carlo techniques to carry out the estimation of posterior probabilities. The program can be used with allozyme, microsatellite, RFLP, SNP, and other kinds of genotype data. We relax several assumptions of early methods for detecting recent immigrants, using genotype data; most significantly, we allow genotype frequencies to deviate from Hardy-Weinberg equilibrium proportions within populations. The program is demonstrated by applying it to two recently published microsatellite data sets for populations of the plant species Centaurea corymbosa and the gray wolf species Canis lupus. A computer simulation study suggests that the program can provide highly accurate estimates of migration rates and individual migrant ancestries, given sufficient genetic differentiation among populations and sufficient numbers of marker loci.     

Mating patterns and genetic diversity in the wild daffodil Narcissus longispathus (Amaryllidaceae)

Despite the importance of Narcissus to ornamental horticulture, there have been no population genetic studies of wild species, many of which have narrow distributions. Here, we measure selfing rates and levels of genetic diversity at allozyme loci in six populations of Narcissus longispathus, a self-compatible daffodil endemic to a few mountain ranges in southeastern Spain. The populations were distributed among four distinct river valleys encompassing two main watersheds in the Sierra de Cazorla mountains. Selfing rates averaged 0.37 (range 0.23-0.46), resulting in significant inbreeding coefficients for the progeny (f = 0.324). In contrast, estimates of inbreeding in parental genotypes were not significantly different from zero (f = 0.001), indicating that few selfed offspring survive to maturity because of inbreeding depression. Species-wide estimates of genetic diversity for the six populations were P(s) = 0.38, H(es) = 0.119 and A(s) = 1.27 with significant genetic differentiation among populations theta = 0.15. The observed patterns of genetic differentiation among populations are likely influenced by the mating system, and a combination of local topography, watershed affinities and gene flow.     

Effects of recent population bottlenecks on reconstructing the demographic history of prairie-chickens

Current methods of DNA sequence analysis attempt to reconstruct historical patterns of population structure and growth from contemporary samples. However, these techniques may be influenced by recent population bottlenecks, which have the potential to eliminate lineages that reveal past changes in demography. One way to examine the performance of these demographic methods is to compare samples from populations before and after recent bottlenecks. We compared estimates of demographic history from populations of greater prairie-chickens (Tympanuchus cupido) before and after recent bottlenecks using four common methods (nested clade analysis [NCA], Tajima's D, mismatch distribution, and MDIV). We found that NCA did not perform well in the presence of bottleneck events, although it did recover some genetic signals associated with increased isolation and the extinction of intermediate populations. The majority of estimates for Tajima's D, including those from bottlenecked populations, were not significantly different from zero, suggesting our data conformed to neutral expectations. In contrast, mismatch distributions including the raggedness index were more likely to identify recently bottlenecked populations with this data set. Estimates of population mutation rate (theta), population divergence time (t), and time to the most recent common ancestor (TMRCA) from MDIV were similar before and after bottlenecks; however, estimates of gene flow (M) were significantly lower in a few cases following a bottleneck. These results suggest that caution should be used when assessing demographic history from contemporary data sets, as recently fragmented and bottlenecked populations may have lost lineages that affect inferences of their demographic history.     

Interregional differentiation of chum salmon from Sakhalin and South Kurils infered from microsatellite markers

Variability at ten microsatellite loci was examined in wild and hatchery populations of chum salmon from the Sakhalin Island and Southern Kuril Islands, Iturup and Kunashir. Substantial genetic differences between Sakhalin and South Kurils chum salmon (the differentiation theta reached 6.0%) were revealed. Statistically significant differences between chum salmon from Iturup and that from Kunashir were demonstrated, as well as between the chum salmon populations from different rivers within the islands. It was shown that in different types of population comparisons, required different marker sets most informative were.     

A method for distinguishing consanguinity and population substructure using multilocus genotype data

We use the patterns of homozygosity at multiple loci to distinguish between excess homozygosity caused by consanguineous mating and that due to undetected population subdivision (the Wahlund effect). Clarification of the underlying causes of excess homozygosity is of practical importance in explaining the occurrence of recessive genetic disorders and in forensic match probability calculations. We calculated a likelihood surface for two parameters: C, the proportion of the population practicing consanguinity, and theta, the genetic correlation due population subdivision. To illustrate the method, we applied it to multilocus genotypic data of two U.K. Asian populations, one practicing a high frequency of cousin marriage, and another in which caste endogamy was suspected. The method was able to successfully distinguish the different patterns of relatedness. The method also returned accurate estimates of C and theta using simulated data sets. We show how our method can be extended to allow for degrees of inbreeding closer than cousin unions, including selfing. With closer inbreeding, the relatedness of recent ancestors beyond the parents becomes an issue.     

Mitochondrial diversity of Opsariichthys bidens (Teleostei, Cyprinidae) in three Chinese drainages

We describe the phylogeographic structure of 28 Chinese populations of the cyprinid Opsariichthys bidens across three main Chinese river drainages. Our study is based on the phylogenetic analysis of the complete mitochondrial cytochrome b gene (1140 bp). We combined this analysis with population processes inferred from nested clade analysis (NCA) and mismatch distributions. Both analyses showed that Chinese O. bidens consists of five mtDNA lineages (Opsariichthys 1-5) with high genetic divergence among them. Molecular divergences (TrN+G) higher than 20% among the Opsariichthys 1-5 mtDNA lineages suggest a taxonomic underestimation at the species level. About 92% of the genetic variance among samples was explained by differences among Opsariichthys mtDNA lineages. Drainage-restricted haplotypes with high frequencies and moderate nucleotide diversity show that Opsariichthys populations have evolved independently. NCA results were congruent with the phylogeny, and unimodal mismatch distributions with negative Tajima's D values suggest population expansions in some Opsariichthys lineages. The phylogeographic structure of the Opsariichthys 1-5 mtDNA lineages appears to be related to their long-term interruption of gene flow (theta(ST)>0.97). Our results suggested that fragmentation of ancestral ranges might have caused Opsariichthys diversification in Chinese waters. However, current distribution of common haplotypes across the Yangtze and Pearl drainages suggests a recent river connection that could have favoured gene flow across drainages. Overall, the results indicated that the richness of current Asian widespread species might have been underestimated, and that the cyprinid populations of O. bidens in the Yangtze, Pearl and Hai He drainages may correspond to five species.     

Morphological and genetic variation in seven species of the endangered Chirostoma "humboldtianum species group" (Atheriniformes: Atherinopsidae)

The Chirostoma "humboldtianum" group includes seven silverside species considered as a monophyletic assemblage because of their high genetic and morphological similarities. The group includes five moderately large species, "peces blancos" (117-300 mm standard length--SL) and two smaller species, "charales" (70-142 mm SL). These species are of great economical, cultural and ichthyological interest for local populations, and their management practices are controversial. We investigated the morphometric, meristic and allozyme variations of the seven species (13 populations) and related the variations with life history, habitat and management procedures. Nineteen morphometric variables, eight meristic variables (by multivariate analysis) and 23 allozyme loci of the seven species and populations of Chirostoma were compared. Principal component analysis (PC) of morphometric and meristic data indicate that both sets of data provided information to differentiate among the seven species. The variables that accounted for most of this differentiation were head length (HL), predorsal 1 length (PIL) and length of pelvic fin base (PfbL). PC and Discriminant Analysis (DA) with morphometric data also suggested the differentiation of populations within C. grandocule (83% correctly classified organisms), whereas PC and DA with meristic data differentiated populations of C. humboldtianum (80% correctly classified organisms). The most important morphometric variables for the differentiation were anal fin height (AfH), length of anal fin base (AfbL) and predorsal 2 length (P2L) and the meristic variables D2fR. PdS and AfR. The genetic variability data indicate changes in values of some of the species in relation to previously reported data. The present populations of C. grandocule show a reduction in He (0.002 vs. 0.009). Other species showed an increase; for instance, C. consocium consocium, C. humboldtianum, C. lucius, C. promelas and C. sphyraena averaged He = 0.069 vs 0.027. theta indicated significant genetic differentiation among the analysed species (0.247, S.D. 0.159) and theta s supported the morphological data that suggest intra-specific differentiation (0.360, S. D. 0.154).     

Bayesian Modeling of Haplotype Effects in Multiparent Populations

A general Bayesian model, Diploffect, is described for estimating the effects of founder haplotypes at quantitative trait loci (QTL) detected in multiparental genetic populations; such populations include the Collaborative Cross (CC), Heterogeneous Socks (HS), and many others for which local genetic variation is well described by an underlying, usually probabilistically inferred, haplotype mosaic. Our aim is to provide a framework for coherent estimation of haplotype and diplotype (haplotype pair) effects that takes into account the following: uncertainty in haplotype composition for each individual; uncertainty arising from small sample sizes and infrequently observed haplotype combinations; possible effects of dominance (for noninbred subjects); genetic background; and that provides a means to incorporate data that may be incomplete or has a hierarchical structure. Using the results of a probabilistic haplotype reconstruction as prior information, we obtain posterior distributions at the QTL for both haplotype effects and haplotype composition. Two alternative computational approaches are supplied: a Markov chain Monte Carlo sampler and a procedure based on importance sampling of integrated nested Laplace approximations. Using simulations of QTL in the incipient CC (pre-CC) and Northport HS populations, we compare the accuracy of Diploffect, approximations to it, and more commonly used approaches based on Haley–Knott regression, describing trade-offs between these methods. We also estimate effects for three QTL previously identified in those populations, obtaining posterior intervals that describe how the phenotype might be affected by diplotype substitutions at the modeled locus.     

A bivariate quantitative genetic model for a linear Gaussian trait and a survival trait

With the increasing use of survival models in animal breeding to address the genetic aspects of mainly longevity of livestock but also disease traits, the need for methods to infer genetic correlations and to do multivariate evaluations of survival traits and other types of traits has become increasingly important. In this study we derived and implemented a bivariate quantitative genetic model for a linear Gaussian and a survival trait that are genetically and environmentally correlated. For the survival trait, we considered the Weibull log-normal animal frailty model. A Bayesian approach using Gibbs sampling was adopted. Model parameters were inferred from their marginal posterior distributions. The required fully conditional posterior distributions were derived and issues on implementation are discussed. The two Weibull baseline parameters were updated jointly using a Metropolis-Hasting step. The remaining model parameters with non-normalized fully conditional distributions were updated univariately using adaptive rejection sampling. Simulation results showed that the estimated marginal posterior distributions covered well and placed high density to the true parameter values used in the simulation of data. In conclusion, the proposed method allows inferring additive genetic and environmental correlations, and doing multivariate genetic evaluation of a linear Gaussian trait and a survival trait.     

HLA variation reveals genetic continuity rather than population group structure in East Asia

Genetic differences between Northeast Asian (NEA) and Southeast Asian (SEA) populations have been observed in numerous studies. At the among-population level, despite a clear north–south differentiation observed for many genetic markers, debates were led between abrupt differences and a continuous pattern. At the within-population level, whether NEA or SEA populations have higher genetic diversity is also highly controversial. In this study, we analyzed a large set of HLA data from East Asia in order to map the genetic variation among and within populations in this continent and to clarify the distribution pattern of HLA lineages and alleles. We observed a genetic differentiation between NEA and SEA populations following a continuous pattern from north to south, and we show a significant and continuous decrease of HLA diversity by the same direction. This continuity is shaped by clinal distributions of many HLA lineages and alleles with increasing or decreasing frequencies along the latitude. These results bring new evidence in favor of the “overlapping model” proposed previously for East Asian peopling history, whereby modern humans migrated eastward from western Eurasia via two independent routes along each side of the Himalayas and, later, overlapped in East Asia across open land areas. Our study strongly suggests that intensive gene flow between NEA and SEA populations occurred and shaped the latitude-related continuous pattern of genetic variation and the peculiar HLA lineage and allele distributions observed in this continent. Probably for a very long period, the exact duration of these events remains to be estimated.     

Advances in Statistical Methods to Map Quantitative Trait Loci in Outbred Populations

Statistical methods to map quantitative trait loci (QTL) in outbred populations are reviewed, extensions and applications to human and plant genetic data are indicated, and areas for further research are identified. Simple and computationally inexpensive methods include (multiple) linear regression of phenotype on marker genotypes and regression of squared phenotypic differences among relative pairs on estimated proportions of identity-by-descent at a locus. These methods are less suited for genetic parameter estimation in outbred populations but allow the determination of test statistic distributions via simulation or data permutation; however, further inferences including confidence intervals of QTL location require the use of Monte Carlo or bootstrap sampling techniques. A method which is intermediate in computational requirements is residual maximum likelihood (REML) with a covariance matrix of random QTL effects conditional on information from multiple linked markers. Testing for the number of QTLs on a chromosome is difficult in a classical framework. The computationally most demanding methods are maximum likelihood and Bayesian analysis, which take account of the distribution of multilocus marker-QTL genotypes on a pedigree and permit investigators to fit different models of variation at the QTL. The Bayesian analysis includes the number of QTLs on a chromosome as an unknown.     

Simple method for analyzing the pattern of DNA polymorphism and its application to SNP data of human

In order to analyze the pattern of DNA polymorphism in detail, we have developed a simple method using a new statistic theta(i) which estimates 4Nmu from the number of segregating sites whose allelic nucleotide frequency is i/n among n DNA sequences, where N is the effective population size and mu is the mutation rate per generation per nucleotide site. Under the assumption that mutations are selectively neutral and a population size is constant, the expectation of theta(i) is equal to that of theta, which estimates 4Nmu from the number of segregating sites, so that the distribution of theta(i) is flat. Therefore, the departure of the distribution of theta(i) from the horizontal line, which represents the value of theta, reflects change in population size and natural selection. Results of the coalescent simulation show that the distributions of theta(i) in the populations which experienced expansion and reduction are U-shaped and upside-down U-shaped, respectively. And the distributions of theta(i) in some populations that experienced bottleneck are W-shaped. Furthermore, we have applied this method to the SNP data in the International HapMap Project. Results of data analyses show that the distributions of theta(i) in the CEU (European), CHB and JPT (Asian) populations are different from that in the YRI population (African). From these results of data analyses in nuclear DNA and the pattern of polymorphism in human mitochondrial DNA already known, we infer that the CEU, CHB and JPT populations experienced the bottleneck.     

How replicable are mRNA expression QTL?

Applying quantitative trait analysis methods to genome-wide microarray-derived mRNA expression phenotypes in segregating populations is a valuable tool in the attempt to link high-level traits to their molecular causes. The massive multiple-testing issues involved in analyzing these data make the correct level of confidence to place in mRNA abundance quantitative trait loci (QTL) a difficult problem. We use a unique resource to directly test mRNA abundance QTL replicability in mice: paired recombinant inbred (RI) and F₂ data sets derived from C57BL/6J (B6) and DBA/2J (D2) inbred strains and phenotyped using the same Affymetrix arrays. We have one forebrain and one striatum data set pair. We describe QTL replication at varying stringencies in these data. For instance, 78% of mRNA expression QTL (eQTL) with genome-wide adjusted p ≤ 0.0001 in RI data replicate at a genome-wide adjusted p < 0.05 or better. Replicated QTL are disproportionately putatively cis-acting, and approximately 75% have higher apparent expression levels associated with B6 genotypes, which may be partly due to probe set generation using B6 sequence. Finally, we note that while trans-acting QTL do not replicate well between data sets in general, at least one cluster of trans-acting QTL on distal Chr 1 is notably preserved between data sets.     

Accuracy and precision of NMR relaxation experiments and MD simulations for characterizing protein dynamics

Model-free parameters obtained from nuclear magnetic resonance (NMR) relaxation experiments and molecular dynamics (MD) simulations commonly are used to describe the intramolecular dynamical properties of proteins. To assess the relative accuracy and precision of experimental and simulated model-free parameters, three independent data sets derived from backbone ¹⁵N NMR relaxation experiments and two independent data sets derived from MD simulations of Escherichia coli ribonuclease HI are compared. The widths of the distributions of the differences between the order parameters for pairs of NMR data sets are congruent with the uncertainties derived from statistical analyses of individual data sets; thus, current protocols for analyzing NMR data encapsulate random uncertainties appropriately. Large differences in order parameters for certain residues are attributed to systematic differences between samples for intralaboratory comparisons and unknown, possibly magnetic field-dependent, experimental effects for interlaboratory comparisons. The widths of distributions of the differences between the order parameters for two NMR sets are similar to widths of distributions for an NMR and an MD set or for two MD sets. The linear correlations between the order parameters for an MD set and an NMR set are within the range of correlations observed between pairs of NMR sets. These comparisons suggest that the NMR and MD generalized order parameters for the backbone amide N—H bond vectors are of comparable accuracy for residues exhibiting motions on a fast time scale (<100 ps). Large discrepancies between NMR and MD order parameters for certain residues are attributed to the occurrence of “rare” motional events over the simulation trajectories, the disruption of an element of secondary structure in one of the simulations, and lack of consensus among the experimental data sets. Consequently, (easily detectable) severe distortions of local protein structure and infrequent motional events in MD simulations appear to be the most serious artifacts affecting the accuracy and precision, respectively, of MD order parameters relative to NMR values. In addition, MD order parameters for motions on a fast (<100 ps) timescale are more precisely determined than their NMR counterparts, thereby permitting more detailed dynamic characterization of biologically important residues by MD simulation than is sometimes possible by experimental methods. Proteins 28:481–493, 1997. © 1997 Wiley-Liss, Inc.