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Biomedical subjects

Marcus W Feldman

Publications and source records attributed to Marcus W Feldman.

44 records · Page 3Linked to original sources

Genetic structure of human populations.

We studied human population structure using genotypes at 377 autosomal microsatellite loci in 1056 individuals from 52 populations. Within-population differences among individuals account for 93 to 95% of genetic variation; differences among major groups constitute only 3 to 5%. Nevertheless, without using prior information about the origins of individuals, we identified six main genetic clusters, five of which correspond to major geographic regions, and subclusters that often correspond to individual populations. General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.

Africa South of the Sahara↗

Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors.

One of the central aims of ecology is to identify mechanisms that maintain biodiversity. Numerous theoretical models have shown that competing species can coexist if ecological processes such as dispersal, movement, and interaction occur over small spatial scales. In particular, this may be the case for non-transitive communities, that is, those without strict competitive hierarchies. The classic non-transitive system involves a community of three competing species satisfying a relationship similar to the children's game rock-paper-scissors, where rock crushes scissors, scissors cuts paper, and paper covers rock. Such relationships have been demonstrated in several natural systems. Some models predict that local interaction and dispersal are sufficient to ensure coexistence of all three species in such a community, whereas diversity is lost when ecological processes occur over larger scales. Here, we test these predictions empirically using a non-transitive model community containing three populations of Escherichia coli. We find that diversity is rapidly lost in our experimental community when dispersal and interaction occur over relatively large spatial scales, whereas all populations coexist when ecological processes are localized.

Antidotes↗

Evolutionary rate in the protein interaction network.

High-throughput screens have begun to reveal the protein interaction network that underpins most cellular functions in the yeast Saccharomyces cerevisiae. How the organization of this network affects the evolution of the proteins that compose it is a fundamental question in molecular evolution. We show that the connectivity of well-conserved proteins in the network is negatively correlated with their rate of evolution. Proteins with more interactors evolve more slowly not because they are more important to the organism, but because a greater proportion of the protein is directly involved in its function. At sites important for interaction between proteins, evolutionary changes may occur largely by coevolution, in which substitutions in one protein result in selection pressure for reciprocal changes in interacting partners. We confirm one predicted outcome of this process-namely, that interacting proteins evolve at similar rates.

Amino Acid Substitution↗

Coevolution of pathogens and cultural practices: a new look at behavioral heterogeneity in epidemics.

The effect of heterogeneity within populations on the spread of infectious diseases has been a recent focus of research. Such heterogeneity may be, for example, spatial, temporal or behavioral in form. Generally, models that include population subdivision have assumed that individuals are permanently assigned to given behavioral states represented by the subpopulations. We consider a simple epidemic model in which a behavioral trait affects disease transmission, and this trait may be transferred among hosts as a consequence of social interaction. This creates a situation where the frequencies of different behavioral traits and disease states as well as their associations may change over time. We consider the impact of the culturally transmitted trait on the criterion for initial spread of the disease. We also explore the evolution of cultural traits in response to pathogen dynamics and show some conditions under which behavioral traits that reduce transmission evolve. We find that behaviors increasing the risk of infection can also evolve when they are inherently favored or when there is sufficient clustering of contacts between like behaviors.

Communicable Diseases↗

Frequentist estimation of coalescence times from nucleotide sequence data using a tree-based partition.

This article proposes a method of estimating the time to the most recent common ancestor (TMRCA) of a sample of DNA sequences. The method is based on the molecular clock hypothesis, but avoids assumptions about population structure. Simulations show that in a wide range of situations, the point estimate has small bias and the confidence interval has at least the nominal coverage probability. We discuss conditions that can lead to biased estimates. Performance of this estimator is compared with existing methods based on the coalescence theory. The method is applied to sequences of Y chromosomes and mtDNAs to estimate the coalescent times of human male and female populations.

Algorithms↗

Evolutionary genetic models of the ovarian time bomb hypothesis for the evolution of genomic imprinting.

At a small number of loci in eutherian mammals, only one of the two copies of a gene is expressed; the other is silenced. Such loci are said to be "imprinted," with some having the maternally inherited allele inactivated and others showing paternal inactivation. Several hypotheses have been proposed to explain how such a genetic system could evolve in the face of the selective advantages of diploidy. In this study, we examine the "ovarian time bomb" hypothesis, which proposes that imprinting arose through selection for reduced risk of ovarian trophoblastic disease in females. We present three evolutionary genetic models that incorporate both this selection pressure and the effect of deleterious mutations to elucidate the conditions under which imprinting could evolve. Our findings suggest that the ovarian time bomb hypothesis can explain why some growth-enhancing genes active in early embryogenesis [e.g., mouse insulin-like growth factor 2 (Igf2)] have evolved to be maternally rather than paternally inactive and why the opposite imprinting status has evolved at some growth-inhibiting loci [e.g., mouse insulin-like growth factor 2 receptor (Igf2r)].

Animals↗

Biodiversity of 52 chicken populations assessed by microsatellite typing of DNA pools.

In a project on the biodiversity of chickens funded by the European Commission (EC), eight laboratories collaborated to assess the genetic variation within and between 52 populations from a wide range of chicken types. Twenty-two di-nucleotide microsatellite markers were used to genotype DNA pools of 50 birds from each population. The polymorphism measures for the average, the least polymorphic population (inbred C line) and the most polymorphic population (Gallus gallus spadiceus) were, respectively, as follows: number of alleles per locus, per population: 3.5, 1.3 and 5.2; average gene diversity across markers: 0.47, 0.05 and 0.64; and proportion of polymorphic markers: 0.91, 0.25 and 1.0. These were in good agreement with the breeding history of the populations. For instance, unselected populations were found to be more polymorphic than selected breeds such as layers. Thus DNA pools are effective in the preliminary assessment of genetic variation of populations and markers. Mean genetic distance indicates the extent to which a given population shares its genetic diversity with that of the whole tested gene pool and is a useful criterion for conservation of diversity. The distribution of population-specific (private) alleles and the amount of genetic variation shared among populations supports the hypothesis that the red jungle fowl is the main progenitor of the domesticated chicken.

Animals↗