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Biomedical subjects

Marcus W Feldman

Publications and source records attributed to Marcus W Feldman.

At least 19 recordsLinked to original sources

Domestication as gene-culture coevolution.

Human preferences can shape the genetic evolution of other species via conservation practices, public health actions, and domestication. While the dynamics of domestication have been explored in depth through empirical and theoretical analyses, few studies have analyzed models for the coevolution of human cultural preferences with the genetics of a domesticate population. Humans shape the fitness landscape of domesticate populations both intentionally and unconsciously, by selecting for desirable traits and modifying environments; in turn, changes in domesticate phenotypes can affect the cultural preferences in the domesticator population. We present a model for the dynamics of domestication which includes interactions between genetic evolution, cultural transmission, and selective pressures. The model includes forms of selection due to culturally transmitted domesticator preferences that can affect the dynamics of domesticate genetic variants, which then affect the dynamics of domesticators. Equilibria with simultaneous genetic and cultural polymorphisms may exist, and may occur under apparent heterozygote disadvantage in the domesticate. Stable quasiperiodic cycles in both domesticates and domesticators are also possible.

Humans↗

Functional genomic analysis of the rates of protein evolution.

The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional genomic data sets yield three main results. First, dispensability and expression have independent, significant effects on the rate of protein evolution. Second, measurements of expression levels in the laboratory can be used to filter data sets of dispensability estimates, removing variates that are unlikely to reflect real biological effects. Third, structural equation models show that although we may reasonably infer that dispensability and expression have significant effects on protein evolutionary rate, we cannot yet accurately estimate the relative strengths of these effects.

Evolution, Molecular↗

On the evolution of epistasis I: diploids under selection.

One interpretation of recent literature on the evolution of phenotypic modularity is that evolution should act to decrease the degree of interaction between genes that contribute to different phenotypes. This issue is addressed directly here using a fitness scheme determined by two genetic loci and a third locus which modifies a measure of statistical interaction between the fitnesses due to the first two. The equilibrium structure of such an epistasis-modifying locus is studied. It is shown that under well-specified conditions a modifying allele that increases epistasis succeeds. In other words, genetic interactions tend to become stronger. It is speculated that this occurs because the mean fitness in such models is locally increasing as a function of the degree of epistasis.

Diploidy↗

Evolution of antibiotic resistance by human and bacterial niche construction.

Antibiotic treatment by humans generates strong viability selection for antibiotic-resistant bacterial strains. The frequency of host antibiotic use often determines the strength of this selection, and changing patterns of antibiotic use can generate many types of behaviors in the population dynamics of resistant and sensitive bacterial populations. In this paper, we present a simple model of hosts dimorphic for their tendency to use/avoid antibiotics and bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic treatment. When a constant fraction of hosts uses antibiotics, the two bacterial strain populations can coexist unless host use-frequency is above a critical value; this critical value is derived as the ratio of the fitness cost of resistance to the fitness cost of undergoing treatment. When strain frequencies can affect host behavior, the dynamics may be analyzed in the light of niche construction. We consider three models underlying changing host behavior: conformism, the avoidance of long infections, and adherence to the advice of public health officials. In the latter two, we find that the pathogen can have quite a strong effect on host behavior. In particular, if antibiotic use is discouraged when resistance levels are high, we observe a classic niche-construction phenomenon of maintaining strain polymorphism even in parameter regions where it would not be expected.

Anti-Bacterial Agents↗

Stable association between strains of Mycobacterium tuberculosis and their human host populations.

Mycobacterium tuberculosis is an important human pathogen in virtually every part of the world. Here we investigate whether distinct strains of M. tuberculosis infect different human populations and whether associations between host and pathogen populations are stable despite global traffic and the convergence of diverse strains of the pathogen in cosmopolitan urban centers. The recent global movement and transmission history of 100 M. tuberculosis isolates was inferred from a molecular epidemiologic study of tuberculosis that spans 12 years. Genetic relationships among these isolates were deduced from the distribution of large genomic deletions, which were identified by DNA microarray and confirmed by PCR and sequence analysis. Phylogenetic analysis of these deletions indicates that they are unique event polymorphisms and that horizontal gene transfer is extremely rare in M. tuberculosis. In conjunction with the epidemiological data, phylogenies reveal three large phylogeographic regions. A host's region of origin is predictive of the strain of tuberculosis he or she carries, and this association remains strong even when transmission takes place in a cosmopolitan urban center outside of the region of origin. Approximate dating of the time since divergence of East Asian and Philippine clades of M. tuberculosis suggests that these lineages diverged centuries ago. Thus, associations between host and pathogen populations appear to be highly stable.

Humans↗

Reconstruction of patrilineages and matrilineages of Samaritans and other Israeli populations from Y-chromosome and mitochondrial DNA sequence variation.

The Samaritan community, which numbered more than a million in late Roman times and only 146 in 1917, numbers today about 640 people representing four large families. They are culturally different from both Jewish and non-Jewish populations in the Middle East and their origin remains a question of great interest. Genetic differences between the Samaritans and neighboring Jewish and non-Jewish populations are corroborated in the present study of 7,280 bp of nonrecombining Y-chromosome and 5,622 bp of coding and hypervariable segment I (HVS-I) mitochondrial DNA (mtDNA) sequences. Comparative sequence analysis was carried out on 12 Samaritan Y-chromosome, and mtDNA samples from nine male and seven female Samaritans separated by at least two generations. In addition, 18-20 male individuals were analyzed, each representing Ethiopian, Ashkenazi, Iraqi, Libyan, Moroccan, and Yemenite Jews, as well as Druze and Palestinians, all currently living in Israel. The four Samaritan families clustered to four distinct Y-chromosome haplogroups according to their patrilineal identity. Of the 16 Samaritan mtDNA samples, 14 carry either of two mitochondrial haplotypes that are rare or absent among other worldwide ethnic groups. Principal component analysis suggests a common ancestry of Samaritan and Jewish patrilineages. Most of the former may be traced back to a common ancestor in the paternally-inherited Jewish high priesthood (Cohanim) at the time of the Assyrian conquest of the kingdom of Israel.

Africa↗

Cultural niche construction and the evolution of small family size.

A model of cultural niche construction with two culturally transmitted traits is examined. The frequency of individuals with a certain general predisposition, which is transmitted vertically, plays a role as the cultural background, or the cultural niche, of the population. The cultural background determines the rate of oblique, relative to vertical, transmission of another cultural trait that affects fertility of individuals. It is assumed that individuals with fewer offspring are more likely to achieve social roles that influence the succeeding generation and are therefore overrepresented as transmitters in the process of oblique transmission. Our model suggests that even a slight overrepresentation of those with fewer offspring can drive the evolution of small family size, provided that the rate of oblique transmission depends strongly on the cultural background. In addition, our model may help to explain the time lag between the decrease in death rates and the subsequent decrease in birth rates during the demographic transition of industrializing societies.

Cultural Characteristics↗

On the meaning of non-epistatic selection.

In population genetics, the additive and multiplicative viability models are often used for the quantitative description of models in which the genetic contributions of several different loci are independent; that is, there is no epistasis. Non-epistasis may also be quantitatively defined in terms of measures of interaction used widely in statistics. Setting these measures of epistasis to zero yields alternative definitions of non-epistasis. We show here that these two definitions of non-epistasis are equivalent; that is, in the most general case of a multilocus, multiallele system, the additive and multiplicative viability models are unique solutions of the additive and multiplicative conditions, respectively, for non-epistasis.

Alleles↗

Evolution of social learning: a mathematical analysis.

Social learning is an important ability seen in a wide range of animals including humans. It has been argued that individual learning, social learning, and innate determination of behavior are favored by natural selection when environmental changes occur at short, intermediate, and long intervals, respectively. Only recently, however, has the hypothesis been examined by means of mathematical models. In this paper, we construct a simple model in which each organism uses one of three genetically determined strategies--it is an individual learner, a social learner or an "innate"--and the three types of organisms are in direct competition with each other. A reduced model, involving only the individual learners and innates, is effectively linear, and we show that by solving the eigenvalue problem of this reduced system we arrive at a good approximation to the global dynamics of the full model. We also study the effect of stochastic environmental changes and reversible mutations among the three strategies. Our results are consistent with the predictions of previous studies. In addition, we identify a critical level of environmental constancy below which only individual and social learners are present.

Animals↗

Gender differences in child survival in contemporary rural China: a county study.

Using data from a survey of deaths of children less than 5 years old conducted in 1997 in a county in Shaanxi Province, China, this paper examines gender differences in child survival in contemporary rural China. First, excess female child mortality in the county in 1994-96 is described, followed by an analysis of the mechanisms whereby the excess mortality takes place, and the underlying social, economic and cultural factors behind it. Excess female child mortality in this county is probably caused primarily by discrimination against girls in curative health care rather than in preventive health care or food and nutrition. Although discrimination occurs in all kinds of families and communities, discrimination itself is highly selective, and is primarily against girls with some specific characteristics. It is argued that the excess mortality of girls is caused fundamentally by the strong son preference in traditional Chinese culture, but exacerbated by the government-guided family planning programme and regulations. This suggests that it is crucial to raise the status of girls within the family and community so as to mitigate the pressures to discriminate against girls in China's low fertility regime. Finally, the possible policy options to improve female child survival in contemporary rural China are discussed.

Adult↗

Robustness of the inference of human population structure: a comparison of X-chromosomal and autosomal microsatellites.

In this paper, data on 20 X-chromosomal microsatellite polymorphisms from the HGDP-CEPH cell line panel are used to infer human population structure. Inferences from these data are compared to those obtained from autosomal microsatellites. Some of the major features of the structure seen with 377 autosomal markers are generally visible with the X-linked markers, although the latter provide less resolution. Differences between the X-chromosomal and autosomal results can be explained without requiring major differences in demographic parameters between males and females. The dependence of the partitioning on the number of individuals sampled from each region and on the number of markers used is discussed.

Analysis of Variance↗

Demographic estimates from Y chromosome microsatellite polymorphisms: analysis of a worldwide sample.

Polymorphisms in microsatellites on the human Y chromosome have been used to estimate important demographic parameters of human history. We compare two coalescent-based statistical methods that give estimates for a number of demographic parameters using the seven Y chromosome polymorphisms in the HGDP-CEPH Cell Line Panel, a collection of samples from 52 worldwide populations. The estimates for the time to the most recent common ancestor vary according to the method used and the assumptions about the prior distributions of model parameters, but are generally consistent with other global Y chromosome studies. We explore the sensitivity of these results to assumptions about the prior distributions and the evolutionary models themselves.

Chromosomes, Human, Y↗

The effect of genetic conflict on genomic imprinting and modification of expression at a sex-linked locus.

We examine how genomic imprinting may have evolved at an X-linked locus, using six diallelic models of selection in which one allele is imprintable and the other is not. Selection pressures are generated by genetic conflict between mothers and their offspring. The various models describe cases of maternal and paternal inactivation, in which females may be monogamous or bigamous. When inactivation is maternal, we examine the situations in which only female offspring exhibit imprinting as well as when both sexes do. We compare our results to those previously obtained for an autosomal locus and to four models in which a dominant modifier of biallelic expression is subjected to the same selection pressures. We find that, in accord with verbal predictions, maternal inactivation of growth enhancers and paternal inactivation of growth inhibitors are more likely than imprinting in the respective opposite directions, although these latter outcomes are possible for certain parameter combinations. The expected outcomes are easier to evolve than the same outcomes for autosomal loci, contradicting the available evidence concerning the direction of imprinting on mammalian sex chromosomes. In most of our models stable polymorphism of imprinting status is possible, a behavior not predicted by verbal accounts.

Animals↗

The effective mutation rate at Y chromosome short tandem repeats, with application to human population-divergence time.

We estimate an effective mutation rate at an average Y chromosome short-tandem repeat locus as 6.9x10-4 per 25 years, with a standard deviation across loci of 5.7x10-4, using data on microsatellite variation within Y chromosome haplogroups defined by unique-event polymorphisms in populations with documented short-term histories, as well as comparative data on worldwide populations at both the Y chromosome and various autosomal loci. This value is used to estimate the times of the African Bantu expansion, the divergence of Polynesian populations (the Maoris, Cook Islanders, and Samoans), and the origin of Gypsy populations from Bulgaria.

Chromosome Mapping↗

Recent duplication of the common carp (Cyprinus carpio L.) genome as revealed by analyses of microsatellite loci.

Genome duplications may have played a role in the early stages of vertebrate evolution, near the time of divergence of the lamprey lineage. Additional genome duplication, specifically in ray-finned fish, may have occurred before the divergence of the teleosts. The common carp (Cyprinus carpio) has been considered tetraploid because of its chromosome number (2n = 100) and its high DNA content. We studied variation using 59 microsatellite primer pairs to better understand the ploidy level of the common carp. Based on the number of PCR amplicons per individual, about 60% of these primer pairs are estimated to amplify duplicates. Segregation patterns in families suggested a partially duplicated genome structure and disomic inheritance. This could suggest that the common carp is tetraploid and that polyploidy occurred by hybridization (allotetraploidy). From sequences of microsatellite flanking regions, we estimated the difference per base between pairs of alleles and between pairs of paralogs. The distribution of differences between paralogs had two distinct modes suggesting one whole-genome duplication and a more recent wave of segmental duplications. The genome duplication was estimated to have occurred about 12 MYA, with the segmental duplications occurring between 2.3 and 6.8 MYA. At 12 MYA, this would be one of the most recent genome duplications among vertebrates. Phylogenetic analysis of several cyprinid species suggests an evolutionary model for this tetraploidization, with a role for polyploidization in speciation and diversification.

Animals↗