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Michael C Whitlock

Publications and source records attributed to Michael C Whitlock.

11 recordsLinked to original sources
PubMed2006

Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans".

Mekel-Bobrov et al. and Evans et al. (Reports, 9 Sept. 2005, p. 1720 and p. 1717, respectively) examined sequence data from modern humans within two gene regions associated with brain development, ASPM and microcephalin, and concluded that selection of these genes must be ongoing. We show that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.

Adaptation, Biological↗
PubMed2005

Probability of fixation in a heterogeneous environment.

We investigate the probability of fixation of a new mutation arising in a metapopulation that ranges over a heterogeneous selective environment. Using simulations, we test the performance of several approximations of this probability, including a new analytical approximation based on separation of the timescales of selection and migration. We extend all approximations to multideme metapopulations with arbitrary population structure. Our simulations show that no single approximation produces accurate predictions of fixation probabilities for all cases of potential interest. At the limits of low and high migration, previously published approximations are found to be highly accurate. The new separation-of-timescales approach provides the best approximations for intermediate rates of migration among habitats, provided selection is not too intense. For nonzero migration and relatively strong selection, all approximations perform poorly. However, the probability of fixation is bounded above and below by the approximations based on low and high migration limits. Surprisingly, in our simulations with symmetric migration, heterogeneous selection in a metapopulation never decreased-and sometimes substantially increased-the probability of fixation of a new allele compared to metapopulations experiencing homogeneous selection with the same mean selection intensity.

Alleles↗
PubMed2004

The incomplete natural history of mitochondria.

Mitochondrial DNA (mtDNA) has been used to study molecular ecology and phylogeography for 25 years. Much important information has been gained in this way, but it is time to reflect on the biology of the mitochondrion itself and consider opportunities for evolutionary studies of the organelle itself and its ecology, biochemistry and physiology. This review has four sections. First, we review aspects of the natural history of mitochondria and their DNA to show that it is a unique molecule with specific characteristics that differ from nuclear DNA. We do not attempt to cover the plethora of differences between mitochondrial and nuclear DNA; rather we spotlight differences that can cause significant bias when inferring demographic properties of populations and/or the evolutionary history of species. We focus on recombination, effective population size and mutation rate. Second, we explore some of the difficulties in interpreting phylogeographical data from mtDNA data alone and suggest a broader use of multiple nuclear markers. We argue that mtDNA is not a sufficient marker for phylogeographical studies if the focus of the investigation is the species and not the organelle. We focus on the potential bias caused by introgression. Third, we show that it is not safe to assume a priori that mtDNA evolves as a strictly neutral marker because both direct and indirect selection influence mitochondria. We outline some of the statistical tests of neutrality that can, and should, be applied to mtDNA sequence data prior to making any global statements concerning the history of the organism. We conclude with a critical examination of the neglected biology of mitochondria and point out several surprising gaps in the state of our knowledge about this important organelle. Here we limelight mitochondrial ecology, sexually antagonistic selection, life-history evolution including ageing and disease, and the evolution of mitochondrial inheritance.

DNA, Mitochondrial↗
PubMed2003

Estimating effective population size and migration rates from genetic samples over space and time.

In the past, moment and likelihood methods have been developed to estimate the effective population size (N(e)) on the basis of the observed changes of marker allele frequencies over time, and these have been applied to a large variety of species and populations. Such methods invariably make the critical assumption of a single isolated population receiving no immigrants over the study interval. For most populations in the real world, however, migration is not negligible and can substantially bias estimates of N(e) if it is not accounted for. Here we extend previous moment and maximum-likelihood methods to allow the joint estimation of N(e) and migration rate (m) using genetic samples over space and time. It is shown that, compared to genetic drift acting alone, migration results in changes in allele frequency that are greater in the short term and smaller in the long term, leading to under- and overestimation of N(e), respectively, if it is ignored. Extensive simulations are run to evaluate the newly developed moment and likelihood methods, which yield generally satisfactory estimates of both N(e) and m for populations with widely different effective sizes and migration rates and patterns, given a reasonably large sample size and number of markers.

Computer Simulation↗
PubMed2003

Fixation probability and time in subdivided populations.

New alleles arising in a population by mutation ultimately are either fixed or lost. Either is possible, for both beneficial and deleterious alleles, because of stochastic changes in allele frequency due to genetic drift. Spatially structured populations differ from unstructured populations in the probability of fixation and the time that this fixation takes. Previous results have generally made many assumptions: that all demes contribute to the next generation in exact proportion to their current sizes, that new mutations are beneficial, and that new alleles have additive effects. In this article these assumptions are relaxed, allowing for an arbitrary distribution among demes of reproductive success, both beneficial and deleterious effects, and arbitrary dominance. The effects of population structure can be expressed with two summary statistics: the effective population size and a variant of Wright's F(ST). In general, the probability of fixation is strongly affected by population structure, as is the expected time to fixation or loss. Population structure changes the effective size of the species, often strongly downward; smaller effective size increases the probability of fixing deleterious alleles and decreases the probability of fixing beneficial alleles. On the other hand, population structure causes an increase in the homozygosity of alleles, which increases the probability of fixing beneficial alleles but somewhat decreases the probability of fixing deleterious alleles. The probability of fixing new beneficial alleles can be simply described by 2hs(1 - F(ST))N(e)/N(tot), where hs is the change in fitness of heterozygotes relative to the ancestral homozygote, F(ST) is a weighted version of Wright's measure of population subdivision, and N(e) and N(tot) are the effective and census sizes, respectively. These results are verified by simulation for a broad range of population structures, including the island model, the stepping-stone model, and a model with extinction and recolonization.

Alleles↗
PubMed2003

The genetics of adaptation: the roles of pleiotropy, stabilizing selection and drift in shaping the distribution of bidirectional fixed mutational effects.

Pleiotropy allows for the deterministic fixation of bidirectional mutations: mutations with effects both in the direction of selection and opposite to selection for the same character. Mutations with deleterious effects on some characters can fix because of beneficial effects on other characters. This study analytically quantifies the expected frequency of mutations that fix with negative and positive effects on a character and the average size of a fixed effect on a character when a mutation pleiotropically affects from very few to many characters. The analysis allows for mutational distributions that vary in shape and provides a framework that would allow for varying the frequency at which mutations arise with deleterious and positive effects on characters. The results show that a large fraction of fixed mutations will have deleterious pleiotropic effects even when mutation affects as little as two characters and only directional selection is occurring, and, not surprisingly, as the degree of pleiotropy increases the frequency of fixed deleterious effects increases. As a point of comparison, we show how stabilizing selection and random genetic drift affect the bidirectional distribution of fixed mutational effects. The results are then applied to QTL studies that seek to find loci that contribute to phenotypic differences between populations or species. It is shown that QTL studies are biased against detecting chromosome regions that have deleterious pleiotropic effects on characters.

Acclimatization↗
PubMed2003

Perspective: Evolution and detection of genetic robustness.

Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness--genetic robustness--and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness: and (3) exploring the implications of genetic robustness for future evolution.

Adaptation, Biological↗
PubMed2002

Environmental stress, inbreeding, and the nature of phenotypic and genetic variance in Drosophila melanogaster.

Fifty-two lines of Drosophila melanogaster founded by single-pair population bottlenecks were used to study the effects of inbreeding and environmental stress on phenotypic variance, genetic variance and survivorship. Cold temperature and high density cause reduced survivorship, but these stresses do not cause repeatable changes in the phenotypic variance of most wing morphological traits. Wing area, however, does show increased phenotypic variance under both types of environmental stress. This increase is no greater in inbred than in outbred lines, showing that inbreeding does not increase the developmental effects of stress. Conversely, environmental stress does not increase the extent of inbreeding depression. Genetic variance is not correlated with environmental stress, although the amount of genetic variation varies significantly among environments and lines vary significantly in their response to environmental change. Drastic changes in the environment can cause changes in phenotypic and genetic variance, but not in a way reliably predicted by the notion of 'stress'.

Animals↗
PubMed2002

Selection, load and inbreeding depression in a large metapopulation.

The subdivision of a species into local populations causes its response to selection to change, even if selection is uniform across space. Population structure increases the frequency of homozygotes and therefore makes selection on homozygous effects more effective. However, population subdivision can increase the probability of competition among relatives, which may reduce the efficacy of selection. As a result, the response to selection can be either increased or decreased in a subdivided population relative to an undivided one, depending on the dominance coefficient F(ST) and whether selection is hard or soft. Realistic levels of population structure tend to reduce the mean frequency of deleterious alleles. The mutation load tends to be decreased in a subdivided population for recessive alleles, as does the expected inbreeding depression. The magnitude of the effects of population subdivision tends to be greatest in species with hard selection rather than soft selection. Population structure can play an important role in determining the mean fitness of populations at equilibrium between mutation and selection.

Animals↗
PubMed2002

Persistence of changes in the genetic covariance matrix after a bottleneck.

Genetic variance, phenotypic variance, and the genetic covariance matrix (G) can change as a result of genetic drift. These changes will persist over time to some extent and will continue if population size remains relatively small. Nine populations founded by a single pair of Drosophila melanogaster were measured for a series of six morphological characteristics for a large number of parent-offspring families at both the third generation after the bottlenecks and after 20 generations. From these data, the phenotypic variance, additive genetic variance, and G were estimated for each line at each generation. Phenotypic and genetic variances were highly correlated over time, so that the measurements made at the third generation were predictive of the state of the population 17 generations later. Genetic covariances were also somewhat stable over time; however, the G matrices of some lines changed significantly over the intervening generations. This change did not return the populations toward their original state before the population bottlenecks. We conclude that the genetic covariance matrix can change as a result of mild genetic drift over a short span of time.

Animals↗