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M W Feldman

Publications and source records attributed to M W Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes.

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.

Biological Evolution↗
PubMed1996

Geographic clustering of human Y-chromosome haplotypes.

Five polymorphic markers on the Y-chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.

Alleles↗
PubMed1996

Population genetic perspectives on the evolution of recombination.

Optimality arguments and modifier theory are reviewed as paradigms for the study of the evolution of recombination. Optimality criteria (such as maximization of mean fitness) may agree with results from models developed in terms of the evolution of recombination at modifier loci. Modifier models demonstrate, however, that equilibrium mean fitness can decrease during the evolution of recombination rates and is not always maximized. Therefore, optimality arguments do not successfully predict the conditions under which increased or decreased recombination will evolve. The results from modifier models indicate that decreased recombination rates are usually favored when the population is initially near a polymorphic equilibrium with linkage disequilibrium. When the population is subject to directional selection or to deleterious mutations, increased recombination may be favored under certain conditions, provided that there is negative epistasis among alleles.

Biological Evolution↗
PubMed1995

Microsatellite variability and genetic distances.

We analyze the within- and between-population dynamics of the distribution of the number of repeats at multiple microsatellite DNA loci subject to stepwise mutation. Analytical expressions for moments up to the fourth order within a locus and the variance of between-locus variance at mutation-drift equilibrium have been obtained. These statistics may be used to test the appropriateness of the one-step mutation model and to detect between-locus variation in the mutation rate. Published data are compatible with the one-step mutation model, although they do not reject the two-step model. Using both multinomial sampling and diffusion approximations for the analysis of the genetic distance introduced by Goldstein et al. [Goldstein, D. B., Linares, A. R., Cavalli-Sforza, L. L. & Feldman, M. W. (1995) Proc. Natl. Acad. Sci. USA 92, 6723-6727], we show that this distance follows a chi 2 distribution with degrees of freedom equal to the number of loci when there is no variation in mutation rates among the loci. In the presence of such variation, the variance of the distance is obtained. We conclude that the number of microsatellite loci required for the construction of phylogenetic trees with reliable branch lengths may be several hundred. Also, mutations that change repeat scores by several units, even though extremely rare, may dramatically influence estimates of population parameters.

DNA, Satellite↗
PubMed1995

Genetic absolute dating based on microsatellites and the origin of modern humans.

We introduce a new genetic distance for microsatellite loci, incorporating features of the stepwise mutation model, and test its performance on microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that it performs well in determining the relations among the primates, but less well than other distance measures (not based on the stepwise mutation model) in determining the relations among closely related human populations. However, the deepest split in the human phylogeny seems to be accurately reconstructed by the new distance and separates African and non-African populations. The new distance is independent of population size and therefore allows direct estimation of divergence times if the mutation rate is known. Based on 30 microsatellite polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15 dinucleotide microsatellites, we estimate that the deepest split in the human phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours requires no external calibration of the rate of molecular evolution. We can use such calibrations, however, to test our estimate.

Animals↗
PubMed1995

High sex ratios in China's future.

In China in recent years, male live births have exceeded those of females by amounts far greater than those that occur naturally in human populations, a trend with significant demographic consequences. The resulting imbalance in the first-marriage market is estimated to be about 1 million males per year after 2010. These "excess" males were not easily accommodated in models with substantial changes in first-marriage patterns. The current sex ratio at birth has little effect on a couple's probability of having at least one son, so future increases in the sex ratio may well occur, especially given increasing access to sex-selective abortion.

China↗
PubMed1995

Sex determination in a symmetric autosomal multi-locus model.

A model of determination of sex by an individual's genotype at n loci is discussed. The parameters that determine the probability that an individual is male (or female) depend only on the loci at which the individual is heterozygous, extending the two-gene theory of Feldman et al. (1991, Genetics 129, 297-312). The analysis uses a set indexation technique that allows a compact expression of the recombination process, and a transformation of the chromosome frequencies that induces a natural subgroup structure on hyperplanes in the frequency simplex. It is shown that the polymorphic equilibria correspond to these subgroups. Conditions are determined under which equilibria that exhibit the even sex ratio are stable. How recombination affects the stability of other equilibria, including those with linkage disequilibrium, are also explored.

Animals↗
PubMed1995

The reduction principle for recombination under density-dependent selection.

In diploid random mating populations with constant viability selection, genetic modifiers of recombination, introduced near equilibria that exhibit genetic association, invade if they reduce recombination. In this study we combine ecological and standard populations genetics in a haploid multilocus model that includes density-dependent regulation of population size and weak density-dependent differential selection among the multilocus genotypes. An allele that affects recombination among the genes contributing to the ecological selection, introduced near a stable equilibrium of the ecological-genetic system, invades if it reduces a weighted average of the recombination rates among pairs of loci under selection. This generalizes the Reduction Principle for the evolution of recombination (M. W. Feldman and U. Liberman, Proc. Nat. Acad. Sci. USA 83, 4824-4827, 1986; L. A. Zhivotovsky, W. M. Feldman, and F. B. Christiansen, Theor. Popul. Biol. 44, 225-245, 1993). It is also shown that the stronger the extent of density-dependence, the weaker the selection for reduced recombination.

Alleles↗
PubMed1995

Effects of cis-trans viability selection on some two-locus models.

Most analyses of two-locus viability models have assumed that the fitness of double heterozygotes are the same whether in the cis or trans configuration. This assumption is unlikely to hold for polymorphic sites within the same locus. We examine the quantitative and qualitative effects of incorporating cis-trans viability differences into a number of deterministic two-locus models. A new result is the finding that two asymmetric equilibria with similar levels of linkage disequilibrium, but different gene frequencies, may arise in quite realistic biological models. The general, and most important, conclusion is that high levels of linkage disequilibrium may be generated by very small selective differences in cis and trans. Polymorphic sites that interact selectively are expected to show high levels of linkage disequilibrium. Conversely, if two polymorphic sites within a gene are found to be in linkage equilibrium, it is likely that one or both are selectively neutral.

Animals↗
PubMed1995

A gene-culture model of human handedness.

A model of handedness incorporating both genetic and cultural processes is proposed, based on an evolutionary analysis, and maximum-likelihood estimates of its parameters are generated. This model has the characteristics that (i) no genetic variation underlies variation in handedness, and (ii) variation in handedness among humans is the result of a combination of cultural and developmental factors, but (iii) a genetic influence remains since handedness is a facultative trait. The model fits the data from 17 studies of handedness in families and 14 studies of handedness in monozygotic and dizygotic twins. This model has the additional advantages that it can explain why monozygotic and dizygotic twins and siblings have similar concordance rates, and no hypothetical selection regimes are required to explain the persistence of left handedness.

Biological Evolution↗
PubMed1995

Population structure, fitness surfaces, and linkage in the shifting balance process.

Wright first introduced the idea that random genetic drift and classical mass-action selection might combine in such a way as to allow populations to find the highest peak in complicated adaptive surfaces. His theory assumes large but structured populations, in which mating is spatially local. If gene flow is sufficiently low, and the subpopulations (demes) are small enough, they will be subject to genetic drift. Distant demes drift independently, allowing many independent searches of the adaptive surface to take place. A deme that has shifted to a higher peak can, by emigration, cause the rest of the demes to shift to the higher peak. The probability of this shift depends on the migration rate. Previous studies have concluded that very little migration is necessary to effect the shift in adaptive peaks that characterizes the last phase of Wright's Shifting Balance Process (SBP). Here we present the results of a computer study that investigates the roles of dispersal distance, the degree of epistasis in the fitness surface, and recombination on the shifting balance process. In particular, we measure their effect on the population's mean fitness. We show that over a range of dispersal distances the advantage of the SBP is a monotonically increasing function of the amount of epistasis. Our results show that the extent of dispersal that results in the greatest effect of the SBP in increasing mean fitness depends on the extent of epistasis. Finally, for low levels of epistasis, higher recombination performs better, while for intermediate levels, lower recombination results in a greater advantage of the SBP.

Adaptation, Biological↗
PubMed1995

An evaluation of genetic distances for use with microsatellite loci.

Mutations of alleles at microsatellite loci tend to result in alleles with repeat scores similar to those of the alleles from which they were derived. Therefore the difference in repeat score between alleles carries information about the amount of time that has passed since they shared a common ancestral allele. This information is ignored by genetic distances based on the infinite alleles model. Here we develop a genetic distance based on the stepwise mutation model that includes allelic repeat score. We adapt earlier treatments of the stepwise mutation model to show analytically that the expectation of this distance is a linear function of time. We then use computer simulations to evaluate the overall reliability of this distance and to compare it with allele sharing and Nei's distance. We find that no distance is uniformly superior for all purposes, but that for phylogenetic reconstruction of taxa that are sufficiently diverged, our new distance is preferable.

Computer Simulation↗
PubMed1994

Evolution of recombination among multiple selected loci: a generalized reduction principle.

Conditions for invasion by a new allele that controls the recombination pattern among an arbitrary number of genes under viability selection are studied. The recombination pattern may include interference. The new allele increases if its appropriately averaged marginal fitness is greater than the mean fitness prior to its introduction. Under weak additive-by-additive epistatic selection, this condition involves a weighted average of the changes in pairwise recombination rates relative to those prior to the introduction of the modifier. The weights here are positive functions of the epistatic selection components. In particular, the modifier allele may succeed even if it increases recombination among some pairs of loci, provided the overall average effect is one of reduction.

Alleles↗
PubMed1994

Cultural transmission of a sign language when deafness is caused by recessive alleles at two independent loci.

Two unlinked autosomal loci are assumed to affect the ability to hear in such a way that homozygosity for the recessive allele at either locus causes deafness. The five deaf genotypes are subject to the same negative selection due to a lower likelihood of marriage, but unmarried deaf persons remain socially active and participate in the cultural transmission of sign languages. Marriages are assortative for deafness or for hearing, and mutation occurs irreversibly from the dominant to recessive allele at each locus at the same rate. At mutation-selection balance, the fully polymorphic equilibrium is symmetrical. Based on this genetic model, we consider the relative importance of various forms of cultural transmission as they affect the persistence of sign languages. Horizontal transmission is shown to be effective when deaf children are able to interact with many peers. This observation is especially pertinent if assortative meeting of deaf children occurs, for example, at schools for the deaf. Oblique transmission can also be effective, but the literature suggests that this kind of transmission plays only a minor role. It is necessary, however, that some form of cultural transmission occur between generations. Thus, vertical transmission is a critical factor, despite the fact that parent-child transmission is often interrupted due to the recessive inheritance of deafness. In particular, the contribution of vertical transmission is enhanced by assortative mating for deafness.

Child Development↗
PubMed1994

Gene-culture coevolution and sex ratios: the effects of infanticide, sex-selective abortion, sex selection, and sex-biased parental investment on the evolution of sex ratios.

The evolutionary consequences of culturally transmitted practices that cause differential mortality between the sexes, thereby distorting the sex ratio (e.g., female infanticide and sex-selective abortion), are explored using dynamic models of gene-culture coevolution. We investigate how a preference for the sex of offspring may affect the selection of genes distorting the primary sex ratio. Sex-dependent differences in mortality have been predicted to select for a male- or female-biased primary sex ratio, to have no effect, or to favor either under different circumstances. We find that when a mating pair's behavior modifies mortality rates in favor of one sex, but does not change the number of offspring produced in the mating, the primary sex ratio will evolve a bias against the favored sex. However, when the total number of offspring of a mating pair is significantly reduced as a consequence of their prejudice, the primary sex ratio will evolve to favor the preferred sex. These results hold irrespective of whether the sex ratio is distorted by the mother's, the father's or the individual's own autosomal genes. The use of dynamic models of gene-culture coevolution allows us to explore the evolution of alleles which distort the sex ratio, as well as the final equilibrium states of the system. Gene-culture interactions can provide equilibria different from those in purely genetic systems, slow the approach to these equilibria by orders of magnitude, and move the primary (PSR) and the adult sex ratio (ASR) away from any stable equilibrium for hundreds of generations.

Abortion, Induced↗