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N H Barton

Publications and source records attributed to N H Barton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Measuring fitness by means of balancer chromosomes.

We present the theoretical background to a new method for measuring genetic variation for total fitness in Drosophila. The method allows heterozygous effects on total fitness of whole wild-type chromosomes to be measured under normal demography with overlapping generations. The wild-type chromosomes are competed against two balancer chromosomes (B1, B2, say), providing a standard genotype B1/B2 against which variation in the fitness effects of the wild-type chromosomes can be assessed. Fitness can be assessed in two ways: (i) at equilibrium of all three chromosomes under heterozygote advantage, and (ii) during displacement of one balancer by the other. Equilibrium with all three chromosomes present will be achieved only if the wild-type homozygote is not too fit, and if the fitnesses of the three heterozygotes are not too unequal. These conditions were not satisfied for any of a sample of 12 lethal-bearing chromosomes isolated from a random-bred laboratory population of Drosophila. At equilibrium, genotypic frequencies show low sensitivity to changes in genotypic fitness. Furthermore, where all four genotypes are viable and fertile, supplementary information from cages with only two chromosomes present and from direct measurements of pre-adult viability are required to estimate fitnesses from frequencies. The invasion method has the advantages of a greater sensitivity and of not requiring further data to estimate fitnesses if the wild-type homozygote is fertile. However, it requires that multiple samples be taken as the invasion progresses. In a discrete generation model, generation time influences fitness estimates from this method and is difficult to estimate accurately from the data. A full age-structured model can also be applied to the data from both types of experiment. For the invasion method, this gives fitness estimates close to those from the discrete generation model.

Adaptation, Physiological↗
PubMed2000

Estimating multilocus linkage disequilibria.

The state of a diploid population segregating for two alleles at each of n loci is described by 22n genotype frequencies, or equivalently, by allele frequencies and by multilocus moments or cumulants of various orders. These measures of linkage disequilibrium cannot usually be determined, both because one cannot tell whether a gene came from the maternal or paternal gamete, and because such a large number of parameters cannot be estimated even from large samples. Simplifying assumptions must therefore be made. This paper sets out methods for estimating multilocus genotype frequencies which are appropriate for unlinked neutral loci, and for populations that are ultimately derived by mixing of two source populations. In such a hybrid population, all multilocus associations depend primarily on the number of loci involved that derive from the maternal genome, and the number derived from the paternal genome. Allele frequencies may differ across loci, and the contribution of each locus to multilocus associations may be scaled by the difference in allele frequency between source populations for that locus (deltap </= 1). For example, the cumulant describing the association between genes i, j, k from the maternal genome, and genes i, l from the paternal genome is kappai,j,k,i*l*, = deltapi2 deltapj deltapk deltapl kappa3,2. The state of the population is described by n allele frequencies; n divergences, deltap; and by a symmetric matrix of cumulants, kappaJ,K (J=0,ellipsis, n, K=0, ellipsis, n). Expressions for these cumulants under short- and long-range migration are given. Two methods for estimating the cumulants are described: a simple method based on multivariate moments, and a maximum likelihood procedure, which uses the Metropolis algorithm. Both methods perform well when tested against simulations with two or four loci.

Algorithms↗
PubMed2000

Detecting bottlenecks and selective sweeps from DNA sequence polymorphism.

A coalescence-based maximum-likelihood method is presented that aims to (i) detect diversity-reducing events in the recent history of a population and (ii) distinguish between demographic (e.g., bottlenecks) and selective causes (selective sweep) of a recent reduction of genetic variability. The former goal is achieved by taking account of the distortion in the shape of gene genealogies generated by diversity-reducing events: gene trees tend to be more star-like than under the standard coalescent. The latter issue is addressed by comparing patterns between loci: demographic events apply to the whole genome whereas selective events affect distinct regions of the genome to a varying extent. The maximum-likelihood approach allows one to estimate the time and strength of diversity-reducing events and to choose among competing hypotheses. An application to sequence data from an African population of Drosophila melanogaster shows that the bottleneck hypothesis is unlikely and that one or several selective sweeps probably occurred in the recent history of this population.

DNA↗
PubMed1999

Clines in polygenic traits.

This article outlines theoretical models of clines in additive polygenic traits, which are maintained by stabilizing selection towards a spatially varying optimum. Clines in the trait mean can be accurately predicted, given knowledge of the genetic variance. However, predicting the variance is difficult, because it depends on genetic details. Changes in genetic variance arise from changes in allele frequency, and in linkage disequilibria. Allele frequency changes dominate when selection is weak relative to recombination, and when there are a moderate number of loci. With a continuum of alleles, gene flow inflates the genetic variance in the same way as a source of mutations of small effect. The variance can be approximated by assuming a Gaussian distribution of allelic effects; with a sufficiently steep cline, this is accurate even when mutation and selection alone are better described by the 'House of Cards' approximation. With just two alleles at each locus, the phenotype changes in a similar way: the mean remains close to the optimum, while the variance changes more slowly, and over a wider region. However, there may be substantial cryptic divergence at the underlying loci. With strong selection and many loci, linkage disequilibria are the main cause of changes in genetic variance. Even for strong selection, the infinitesimal model can be closely approximated by assuming a Gaussian distribution of breeding values. Linkage disequilibria can generate a substantial increase in genetic variance, which is concentrated at sharp gradients in trait means.

Alleles↗
PubMed1999

Hemochromatosis probands as blood donors.

BACKGROUND: There has been no estimate of the potential eligibility of hemochromatosis probands or patients as blood donors or the suitability for transfusion of their blood that was removed by therapeutic phlebotomy. STUDY DESIGN AND METHODS: According to guidelines of the American Association of Blood Banks, a retrospective estimate of these factors in 211 adult white hemochromatosis probands diagnosed during routine medical care was performed. The findings were compared to those in volunteer white whole-blood donors. RESULTS: Before diagnosis of hemochromatosis, 49 probands had voluntarily donated 597 units of blood; 88 percent were donated by men. After diagnosis, 142 (67%) of 211 probands were potentially eligible. Data on each unit removed during iron-depletion therapy and during the first year of maintenance therapy (therapeutic phlebotomy) were available in 86 eligible probands. Of 1592 units, 1029 (65%) obtained during iron-depletion therapy in eligible probands were potentially suitable; 86 percent were from men. During maintenance therapy, 106 (88%) of 121 units from eligible probands were potentially suitable. In volunteer donors, 255,567 (94%) of 273,302 presenting donors were accepted. After testing and laboratory losses, 239,300 (94%) units were acceptable for transfusion. CONCLUSIONS: In comparison with normal volunteers, hemochromatosis probands at diagnosis are less likely to be eligible as blood donors. The percentage of units obtained from patients during iron-depletion therapy that are suitable for transfusion is also lower, although the percentage increases during maintenance therapy.

Adult↗
PubMed1999

Introgression through rare hybridization: A genetic study of a hybrid zone between red and sika deer (genus Cervus) in Argyll, Scotland.

In this article we describe the structure of a hybrid zone in Argyll, Scotland, between native red deer (Cervus elaphus) and introduced Japanese sika deer (Cervus nippon), on the basis of a genetic analysis using 11 microsatellite markers and mitochondrial DNA. In contrast to the findings of a previous study of the same population, we conclude that the deer fall into two distinct genetic classes, corresponding to either a sika-like or red-like phenotype. Introgression is rare at any one locus, but where the taxa overlap up to 40% of deer carry apparently introgressed alleles. While most putative hybrids are heterozygous at only one locus, there are rare multiple heterozygotes, reflecting significant linkage disequilibrium within both sika- and red-like populations. The rate of backcrossing into the sika population is estimated as H = 0.002 per generation and into red, H = 0.001 per generation. On the basis of historical evidence that red deer entered Kintyre only recently, a diffusion model evaluated by maximum likelihood shows that sika have increased at approximately 9.2% yr-1 from low frequency and disperse at a rate of approximately 3.7 km yr-1. Introgression into the red-like population is greater in the south, while introgression into sika varies little along the transect. For both sika- and red-like populations, the degree of introgression is 30-40% of that predicted from the rates of current hybridization inferred from linkage disequilibria; however, in neither case is this statistically significant evidence for selection against introgression.

Alleles↗
PubMed1999

A comparison of multilocus clines maintained by environmental adaptation or by selection against hybrids.

There has recently been considerable debate over the relative importance of selection against hybrids ("endogenous" selection) vs. adaptation to different environments ("exogenous") in maintaining stable hybrid zones and hence in speciation. Single-locus models of endogenous and exogenous viability selection generate clines of similar shape, but the comparison has not been extended to multilocus systems, which are both quantitatively and qualitatively very different from the single-locus case. Here we develop an analytical multilocus model of differential adaptation across an environmental transition and compare it to previous heterozygote disadvantage models. We show that the shape of clines generated by exogenous selection is indistinguishable from that generated by endogenous selection. A stochastic simulation model is used to test the robustness of the analytical description to the effects of drift and strong selection, and confirms the prediction that pairwise linkage disequilibria are predominantly generated by migration. However, although analytical predictions for the width of clines maintained by heterozygote disadvantage fit well with the simulation results, those for environmental adaptation are consistently too narrow; reasons for the discrepancy are discussed. There is a smooth transition between a system in which a set of loci effectively act independently of each other and one in which they act as a single nonrecombining unit.

Adaptation, Physiological↗
PubMed1998

Why sex and recombination?

REVIEW Most higher organisms reproduce sexually, despite the automatic reproductive advantage experienced by asexual variants. This implies the operation of selective forces that confer an advantage to sexuality and genetic recombination, at either the population or individual level. The effect of sex and recombination in breaking down negative correlations between favorable variants at different genetic loci, which increases the efficiency of natural selection, is likely to be a major factor favoring their evolution and maintenance. Various processes that can cause such an effect have been studied theoretically. It has, however, so far proved hard to discriminate among them empirically.

Animals↗
PubMed1998

Testing for epistasis between deleterious mutations.

Determining the way in which deleterious mutations interact in their effects on fitness is crucial to numerous areas in population genetics and evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last (synergistic epistasis), then the evolution of sex and recombination may be favored to facilitate the elimination of deleterious mutations. However, there is a severe shortage of relevant data. Three relatively simple experimental methods to test for epistasis between deleterious mutations in haploid species have recently been proposed. These methods involve crossing individuals and examining the mean and/or skew in log fitness of the offspring and parents. The main aim of this paper is to formalize these methods, and determine the most effective way in which tests for epistasis could be carried out. We show that only one of these methods is likely to give useful results: crossing individuals that have very different numbers of deleterious mutations, and comparing the mean log fitness of the parents with that of their offspring. We also reconsider experimental data collected on Chlamydomonas moewussi using two of the three methods. Finally, we suggest how the test could be applied to diploid species.

Animals↗
PubMed1997

Genetic variation for total fitness in Drosophila melanogaster.

We measured the heterozygous effects on net fitness of a sample of 12 wild-type third chromosomes in D. melanogaster. Effects on fitness were assessed by competing the wild-type chromosomes against balancer chromosomes, to prevent the production of recombinants. The measurements were carried out in the population cage environment in which the life history had been evolving, in an undisturbed population with overlapping generations, and replicated measurements were made on each chromosome to control for confounding effects such as mutation accumulation. We found significant variation among the wild type chromosomes in their additive genetic effect on net fitness. The system provides an opportunity to obtain an accurate estimate of the distribution of heterozygous effects on net fitness, the contribution of different fitness components including male mating success, and the role of intra-chromosomal epistasis in fitness variation.

Animals↗
PubMed1997

The strength of indirect selection on female mating preferences.

An important but controversial class of hypotheses concerning the evolution of female preferences for extreme male mating displays involves "indirect selection." Even in the absence of direct fitness effects, preference for males with high overall fitness can spread via a genetic correlation that develops between preference alleles and high fitness genotypes. Here we develop a quantitative expression for the force of indirect selection that (i) applies to any female mating behavior, (ii) is relatively insensitive to the underlying genetics, and (iii) is based on measurable quantities. In conjunction with the limited data now available, it suggests that the evolutionary force generated by indirect selection on preferences is weak in absolute terms. This finding raises the possibility that direct selection on preference genes may often be more important than indirect selection, but more data on the quantities identified by our model and on direct selection are needed to decide the question.

Animals↗
PubMed1997

Diagnosis of hemochromatosis probands in a community hospital.

PURPOSE: To evaluate factors that lead to the diagnosis of hemochromatosis probands in a community hospital, including education of physicians about hemochromatosis and iron overload, specialty of physicians, diagnostic indicators of hemochromatosis, and clinical manifestations of hemochromatosis probands. PATIENTS AND METHODS: We conducted a hemochromatosis education program for health care personnel associated with a community hospital and the public during 1990 to 1994. Data on physicians who diagnosed probands, diagnostic indicators of hemochromatosis, and manifestations of hemochromatosis and associated illnesses were tabulated. Iron grades of all hospital liver biopsy specimens obtained from Caucasian subjects during 1990 to 1994 were also analyzed. RESULTS: We identified 162 hemochromatosis probands; 66.7% were diagnosed by physicians who participated in our education program. Primary care and internal medicine subspecialty physicians diagnosed 66.7% and 29.6% of probands, respectively, based on elevated serum iron parameters and hepatic enzyme concentrations (51.9% and 36.4% of probands, respectively). Iron overload occurred in 90.7%, and was associated with clinical manifestations in most. Of 844 hospital liver biopsy specimens from Caucasians, 8.5% had increased iron grades; 4.6% represented hemochromatosis. CONCLUSIONS: Physicians with current education readily diagnose hemochromatosis probands during routine health care delivery, but most probands identified in this manner have iron overload. Our results suggest that community physicians and hospitals could contribute substantially to hemochromatosis screening programs, permitting detection of more homozygotes before the development of iron overload.

Adolescent↗
PubMed1997

The spread of an advantageous allele across a barrier: the effects of random drift and selection against heterozygotes.

A local barrier to gene flow will delay the spread of an advantageous allele. Exact calculations for the deterministic case show that an allele that is favorable when rare is delayed very little even by a strong barrier: its spread is slowed by a time proportional to log((B/sigma) square root of 2S)/S, where B is the barrier strength, sigma the dispersal range, and fitnesses are 1:1 + S:1 + 2S. However, when there is selection against heterozygotes, such that the allele cannot increase from low frequency, a barrier can cause a much greater delay. If gene flow is reduced below a critical value, spread is entirely prevented. Stochastic simulations show that with additive selection, random drift slows down the spread of the allele, below the deterministic speed of sigma square root of 2S. The delay to the advance of an advantageous allele caused by a strong barrier can be substantially increased by random drift and increases with B/(2S rho sigma 2) in a one-dimensional habitat of density rho. However, with selection against heterozygotes, drift can facilitate the spread and can free an allele that would otherwise be trapped indefinitely by a strong barrier. We discuss the implications of these results for the evolution of chromosome rearrangements.

Alleles↗
PubMed1997

The effective size of a subdivided population.

This paper derives the long-term effective size, Ne, for a general model of population subdivision, allowing for differential deme fitness, variable emigration and immigration rates, extinction, colonization, and correlations across generations in these processes. We show that various long-term measures of Ne are equivalent. The effective size of a metapopulation can be expressed in a variety of ways. At a demographic equilibrium, Ne can be derived from the demography by combining information about the ultimate contribution of each deme to the future genetic make-up of the population and Wright's FST's. The effective size is given by Ne = 1/(1 + var (upsilon) ((1 - FST)/Nin), where n is the number of demes, theta i is the eventual contribution of individuals in deme i to the whole population (scaled such that sigma theta i = n), and < > denotes an average weighted by theta i. This formula is applied to a catastrophic extinction model (where sites are either empty or at carrying capacity) and to a metapopulation model with explicit dynamics, where extinction is caused by demographic stochasticity and by chaos. Contrary to the expectation from the standard island model, the usual effect of population subdivision is to decrease the effective size relative to a panmictic population living on the same resource.

Models, Genetic↗
PubMed1997

The evolution of recombination: removing the limits to natural selection.

One of the oldest hypotheses for the advantage of recombination is that recombination allows beneficial mutations that arise in different individuals to be placed together on the same chromosome. Unless recombination occurs, one of the beneficial alleles is doomed to extinction, slowing the rate at which adaptive mutations are incorporated within a population. We model the effects of a modifier of recombination on the fixation probability of beneficial mutations when beneficial alleles are segregating at other loci. We find that modifier alleles that increase recombination do increase the fixation probability of beneficial mutants and subsequently hitchhike along as the mutants rise in frequency. The strength of selection favoring a modifier that increases recombination is proportional to lambda(2)S delta r/r when linkage is tight and lambda(2)S3 delta r/N when linkage is loose, where lambda is the beneficial mutation rate per genome per generation throughout a population of size N, S is the average mutant effect, r is the average recombination rate, and delta r is the amount that recombination is modified. We conclude that selection for recombination will be substantial only if there is tight linkage within the genome or if many loci are subject to directional selection as during periods of rapid evolutionary change.

Biological Evolution↗
PubMed1996

Speciation: more than the sum of the parts.

Genetic studies are beginning to provide insights into the evolutionary processes that reduce the fitness of hybrids between recently diverged species. However, the deleterious gene interactions responsible for this fitness reduction are still poorly understood.

Animals↗