On the correlation between heterozygosity and fitness in natural populations

Three primary hypotheses currently prevail for correlations between heterozygosity at a set of molecular markers and fitness in natural populations. First, multilocus heterozygosity-fitness correlations might result from selection acting directly on the scored loci, such as at particular allozyme loci. Second, significant levels of linkage disequilibrium, as in recently bottlenecked-and-expanded populations, might cause associations between the markers and fitness loci in the local chromosomal vicinity. Third, in partially inbred populations, heterozygosity at the markers might reflect variation in the inbreeding coefficient and might associate with fitness as a result of effects of homozygosity at genome-wide distributed loci. Despite years of research, the relative importance of these hypotheses remains unclear. The screening of heterozygosity at polymorphic DNA markers offers an opportunity to resolve this issue, and relevant empirical studies have now emerged. We provide an account of the recent progress on the subject, and give suggestions on how to distinguish between the three hypotheses in future studies.     

Simulating allele frequencies in a population and the genetic differentiation of populations under mutation pressure

A method is developed for simulating the allele frequencies in an equilibrium or transient population under the effects of neutral mutation and random drift. The method is based on diffusion theory and is fast so that it can be used to study in detail the distribution of heterozygosity or any quantity that can be expressed as a function of allele frequencies. It has been applied to study the distribution of heterozygosity and the distributions of the frequencies of the first three most frequent alleles in a population. It also has been applied to study the distribution of the number of alleles shared by two populations that were derived from a common stock.     

Relationship between heterozygosity and genetic distance in the three major races of man

In pairwise comparisons of gene frequency data from the three major races of man, the single locus measures of the heterozygosity within and the genetic distance between races are shown to be strongly correlated across the loci coding for red cell proteins and enzymes. The intercept of the regression line of genetic distance on heterozygosity in protein enzyme loci is statistically insignificant. These findings suggest that the genetic variability at the enzyme and protein loci in man is probably maintained by a balance of mutation and random genetic drift. At the blood group loci, however, the observed relationship between genetic distance and heterozygosity does not follow the expectation of the neutral mutation hypothesis. These observations are discussed in terms of the changes in probability of identical monomorphism in two populations during the process of gene differentiation.     

Effect of changes in population size on the correlation between mutation rate and heterozygosity

Summary The effect of changes in population size on the correlation between mutation rate and heterozygosity was studied by using two models: sudden change in population size and gradual change. It was shown that the results for the two models are close to each other, unless the rate of change for the latter is exceedingly slow. Thus, in many cases, the former model, which is much simpler than the latter, can be used to treat the present problem. Numerical computations showed that the correlation in a population that is expanding or has expanded in the recent past is stronger while the correlation in a population that is decreasing or has experienced a population reduction or bottleneck in the recent past is weaker than that for an equilibrium population with the same mean heterozygosity. However, regardless of whether the population is at equilibrium or not, the proportion of variation in heterozygosity that is attributable to variation in molecular weight over loci is rather small if the mean heterozygosity of the population is low, say of the order 0.05 or smaller.     

Relationships among genetic distance,forage yield and heterozygosity in isogenic diploid and tetraploid alfalfa populations

Isogenic diploid and tetraploid alfalfa (Medicago sativa L.) was studied with molecular markers to help understand why diploid performance and breeding behavior does not always predict that of tetraploids. In a previous study of partially heterozygous alfalfa genotypes, we detected a low correlation between yields of isogenic diploid (2x) and tetraploid (4x) single-cross progenies, and genetic distances were more highly correlated with yields of tetraploids than diploids. These differences may be related to the level of RFLP heterozygosity expected among progenies derived from heterozygous parents at the two ploidy levels. The objectives of this study were to determine the relationships among genetic distance, forage yield and heterozygosity in isogenic 2 x and 4 x alfalfa populations. Four diploid genotypes were chromosome doubled to produce corresponding isogenic autotetraploids, and these genotypes were mated in 4 × 4 diallels to produce 6 single-cross families at each ploidy level for field evaluation. Allele compositions of parents were determined at 33 RFLP loci by monitoring segregation of homologous restriction fragments among individuals within progenies, and these were used to estimate RFLP heterozygosity levels for all single-cross progenies at both ploidy levels. RFLP heterozygosity rankings were identical between progenies of isogenic diploid and tetraploid parents; but significant associations (P < 0.05) between estimated heterozygosity levels and forage yield were detected only at the tetraploid level. Since tetraploid families were nearly 25% more heterozygous than the corresponding diploid families, inconsistencies in the association between molecular marker diversity and forage yields of isogenic 2 x and 4 x single crosses may be due to recessive alleles that are expressed in diploids but masked in tetraploids. The gene action involved in heterosis may be the same at both ploidy levels; however, tetraploids benefit from greater complementary gene interactions than are possible for equivalent diploids. Present address: AgResearch Grasslands, New Zealand Pastoral Agriculture Research Institute, Palmerston North, New Zealand     

Composite stepwise mutation model under the neutral mutation hypothesis

Summary As an extension of the conventional (Ohta-Kimura) stepwise mutation model, a new model is proposed. In this model, it is assumed that each charge state (electromorph) is represented byK alleles and that a mutation changes an allele either by one step in the charge space or to one of the other members of the identical electromorph. It is shown that the net genetic variability within a population is similar to that predicted by the infinite-allele model (Kimura-Crow model) rather than to that predicted by the stepwise mutation model, and theK-dependence of genetic variability is rather weak whenK 2 and the effective population size is not much greater than the reciprocal of mutation rate. The results are compared with the recent observations at the xanthine dehydrogenase locus inDrosophila pseudoobscura. Contribution No. 1218 from the National Institute of Genetics, Mishima, 411, Japan.     

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.     

A note on the correlation between heterozygosity and recombination rate

Mechanisms responsible for the correlation between heterozygosity and recombination rate have been thought to be background selection and selective sweep. In addition to these two, diversity enhancing selection and/or gene conversion is suggested to be contributing to the correlation, by surveying some examples of highly polymorphic loci that tend to locate in high-recombination regions.     

Estimation of average heterozygosity and genetic distance from a small number of individuals

The magnitudes of the systematic biases involved in sample heterozygosity and sample genetic distances are evaluated, and formulae for obtaining unbiased estimates of average heterozygosity and genetic distance are developed. It is also shown that the number of individuals to be used for estimating average heterozygosity can be very small if a large number of loci are studied and the average heterozygosity is low. The number of individuals to be used for estimating genetic distance can also be very small if the genetic distance is large and the average heterozygosity of the two species compared is low.     

Dynamics of microsatellite divergence under stepwise mutation and proportional slippage/point mutation models

Recently Kruglyak, Durrett, Schug, and Aquadro showed that microsatellite equilibrium distributions can result from a balance between polymerase slippage and point mutations. Here, we introduce an elaboration of their model that keeps track of all parts of a perfect repeat and a simplification that ignores point mutations. We develop a detailed mathematical theory for these models that exhibits properties of microsatellite distributions, such as positive skewness of allele lengths, that are consistent with data but are inconsistent with the predictions of the stepwise mutation model. We use our theoretical results to analyze the successes and failures of the genetic distances (delta(mu))(2) and D(SW) when used to date four divergences: African vs. non-African human populations, humans vs. chimpanzees, Drosophila melanogaster vs. D. simulans, and sheep vs. cattle. The influence of point mutations explains some of the problems with the last two examples, as does the fact that these genetic distances have large stochastic variance. However, we find that these two features are not enough to explain the problems of dating the human-chimpanzee split. One possible explanation of this phenomenon is that long microsatellites have a mutational bias that favors contractions over expansions.     

Variance in quantitative traits due to linked dominant genes and variance in heterozygosity in small populations

The influence of small population size (N) on the genetic variance within and between randomly bred unselected lines, with selfing permitted, is investigated for a model of a quantitative trait determined by linked genes that show dominance within loci but are additive over loci. Formulae for within-line variance include terms in linkage disequilibrum, which occurs by chance in the lines and these are evaluated in terms of N, map length and gene number.—The expected variance within lines is increased by this disequilibrium, quite substantially if there are many loci, with most of the increase being between or within full-sib families and almost no change expected between half-sib families or in the covariance of offspring and parent. If all loci are unlinked, there is no increase in variance within full-sib families. The variance between lines is little affected by disequilibrum generated by chance.—Expressions for the variance between individuals in heterozygosity over the whole genome are special cases of those for the variance due to linked dominated genes, and formulae are given and evaluated. The coefficient of variation of heterozygosity is at least (see PDF) and can be much higher for species with few chromosomes.     

The ecology and genetics of fitness in Chlamydomonas. X. The relationship between genetic correlation and genetic distance

Abstract.— A necessary condition for the maintenance of genetic variation in heterogenous environments is that the relative fitnesses of a collection of genotypes vary as conditions of growth change. This can be detected by estimating the amount of gene-by-environment interaction (G X E) when a range of types are tested across a range of conditions. However it is the sign and magnitude of the genetic correlation, which is a component of G X E, that governs the ultimate fate of variation. Whether genetic variation will be preserved, then, depends on how the genetic correlation changes as a function of the ecological differences among environments and the genetic differences among genotypes. To evaluate this, we assayed the performance of 15 chlorophyte species of known genetic relation in 20 environments. We found that the quantity of G X E increased as both the environmental variance across environments and the genetic distance increased. Moreover the genetic correlation declined as the environmental variance between pairs of environments and the genetic distance between pairs of genotypes increased. These results suggest that divergent selection will be more likely to maintain genetic variation when environments are strongly contrasted and genotypes widely divergent.     

On the question of correlation between the size of the epigenetic distance and the degree of allopatry in different populations

The frequencies of discontinuous-varying traits in a Protoslav population (9th century) and an Alamannic population (6th to 8th century) were compared with one another because of their known degree of allopatry. The correlation between this degree of allopatry and the size of epigenetic distance has been shown. Some arguments, e.g. directed gene flow for the calculated distances, have also been discussed.     

Relations between genetic distance of parental pig breeds and heterozygosity of their F1 crosses measured by genetic markers

The aim of this paper is to examine the extent to which increment of heterozygosity in F₁ crosses can be predicted from genetic distance of parental breeds. For this purpose, 38 polymorphic marker loci (blood groups, allotypes, polymorphic proteins and enzymes) were tested in 1115 purebred animals (Duroc, Hampshire and Czech Meat Pig as sire breeds; Landrace, Large White and Black Pied Přeštice as dam breeds) and in 1428 crossbred animals of the resulting nine crossbred groups. The number of animals in each genetic group ranged from 75 to 230. On the basis of the allele frequencies of the scored loci, three measures of genetic diversity (heterozygosity, standardized heterozygosity, effective number of alleles) were calculated in all 15 genetic groups. Furthermore, two measures of genetic distance (Nei's standard genetic distance and Gregorius' absolute genetic distance) were calculated between the parental populations. High correlations (Pearson product-moment correlation 0.62 to 0.73; Spearman rank correlation 0.58 to 0.85) were found between the increment of heterozygosity in the crosses (in relation to the mean of the heterozygosities of parental populations) and the genetic distance between the parental populations.     

High correlation between the turnover of nucleotides under mutational pressure and the DNA composition

Background  

Any DNA sequence is a result of compromise between the selection and mutation pressures exerted on it during evolution. It is difficult to estimate the relative influence of each of these pressures on the rate of accumulation of substitutions. However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa.