The cytogenetics of mutator gene-induced X-linked lethals in Drosophila melanogaster

A third chromosome mutator gene effectively increases the spontaneous frequency of sex-linked recessive lethals in females but not in females of Drosophila melanogaster. Approximately half the mutator-induced mutants occur as clusters of the same mutant implying a premeiotic origin. An appreciable number of the mutator-induced lethals are associated with comparatively long deficiencies of several salivary gland chromosome bands. The possible modes of mutator gene action are conjectured.     

Effects of reproductive compensation, gamete discounting and reproductive assurance on mating-system diversity in hermaphrodites

Hermaphroditism allows considerable scope for contributing genes to subsequent generations through various mixtures of selfed and outcrossed offspring. The fitness consequences of different family compositions determine the evolutionarily stable mating strategy and depend on the interplay of genetic features, the nature of mating, and factors that govern offspring development. This theoretical article considers the relative contributions of these influences and their interacting effects on mating-system evolution, given a fixed genetic load within a population. Strong inbreeding depression after offspring gain independence selects for exclusive outcrossing, regardless of the intensity of predispersal inbreeding depression, unless insufficient mating limits offspring production. The extent to which selfing evolves under weak postdispersal inbreeding depression depends on predispersal inbreeding depression and the opportunity for resource limitation of offspring production. Mixed selfing and outcrossing is an evolutionarily stable strategy (ESS) if selfed zygotes survive poorly, but selfed offspring survive well, and maternal individuals produce enough "extra" eggs that deaths of unviable outcrossed embryos do not impact offspring production (reproductive compensation). Mixed mating can also be an ESS, despite weak lifetime inbreeding depression, if self-mating reduces the number of male gametes available for outcrossing (male-gamete discounting). Reproductive compensation and male-gamete discounting act largely independently on mating-system evolution. ESS mating systems always involve either complete fertilization or fertilization of enough eggs to induce resource competition among embryos, so although reproductive assurance is adaptive with insufficient mating, it is never an ESS. Our results illustrate the theoretical importance of different constraints on offspring production (availability of male gametes, egg production, and maternal resources) for both the course and outcome of mating-system evolution, whereas unequal competition between selfed and outcrossed embryos has limited effect. These results also underscore the significance of heterogeneity in the nature and intensity of inbreeding depression during the life cycle for the evolution of hermaphrodite mating systems.     

Effects of genetic drift on variance components under a general model of epistasis

We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(delta(z)) = sigma(n)k=1 FkV(A(k)), where n is the number of loci contributing to the trait variance, V(A(1)) = V(A) is the additive genetic variance, and V(A(k)) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*(A)), is closely related to var(delta(z)); (V*(A)) = (1 - F) sigma(n)k=1 kFk-1V(A(k)). Thus, epistasis inflates the expected additive variance above V(A)(1 - F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*(AA. This is not true in general with diploidy, because dominance alone can reduce (V*(A)) below V(A)(1 - F) (e.g., when dominant alleles are rare). Without dominance, diploidy produces simple expressions: var(delta(z)) = sigma(n)k=1 (2F)kV(A(k)) and (V(A)) = (1 - F) sigma(n)k=1 k(2F)k-1V(A(k)). With dominance (and even without epistasis), var(delta(z)) and (V*(A)) no longer depend solely on the variance components in the base population. For small F, the expected additive variance simplifies to (V*(A)) approximately equal to (1 - F)V(A) + 4FV(AA) + 2FV(D) + 2FC(AD), where C(AD) is a sum of two terms describing covariances between additive effects and dominance and additive X dominance interactions. Whether population bottlenecks lead to expected increases in additive variance depends primarily on the ratio of nonadditive to additive genetic variance in the base population, but dominance precludes simple predictions based solely on variance components. We illustrate these results using a model in which genotypic values are drawn at random, allowing extreme and erratic epistatic interactions. Although our analyses clarify the conditions under which drift is expected to increase V(A), we question the evolutionary importance of such increases.     

Random genetic drift and gamete frequency

An analytic expression of conditional expectation of transient gamete frequency, given that one of the two loci remains polymorphic, is obtained in terms of the diffusion process by calculating the moments of the distribution. Using this expression, a model where linkage disequilibrium is introduced by a single mutation is considered. The conditional expectation of the gamete frequency given that the locus with the mutant allele remains polymorphic is presented. The behavior is significantly different from the monotonic decrease observed in the deterministic model without random genetic drift.     

X-linked genetic homologies between mouse and man

X-linked genes are conserved among all mammalian species, but the organization of genes on the X chromosome varies from one species to another. This review summarizes the evidence for established gene homologies between mice and human beings. It also describes genes that are possible homologies because of their locations in the human and murine X chromosomes and similarities in the phenotypes they produce. Based on current knowledge of homologous gene location, the human and murine X chromosomes appear to contain four highly conserved segments and differ in organization by only three to four simple chromosomal rearrangements.     

Dosage compensation of X-linked heat-shock puffs in Drophila pseudoobscura

Four major puffs are inducible by heat shock in the larval salivary gland chromosomes of D. pseudoobscura. Two of these puffs are present at 23 and 39–40 on the right arm of the X chromosome and two are present at 53 and 58 on chromosome 2. By means of in situ hybridization, residual homologies were demonstrated between the puffs at 23 in D. pseudoobscura and at 63C in D. melanogaster, and between the two chromosome 2 puffs of D. pseudoobscura and 87A and 87C of D. melanogaster. RNA synthesis was monitored as a function of ³H-uridine incorporation in the major heat-induced puffs of D. pseudoobscura and was found to be equivalent in males and females indicating dosage compensation of the two X-linked loci. The evolution of the regulatory controls of these genes is discussed.     

Gene flow and genetic drift in urban environments

Evidence is growing that human modification of landscapes has dramatically altered evolutionary processes. In urban population genetic studies, urbanization is typically predicted to act as a barrier that isolates populations of species, leading to increased genetic drift within populations and reduced gene flow between populations. However, urbanization may also facilitate dispersal among populations, leading to higher genetic diversity within, and lower differentiation between, urban populations. We reviewed the literature on nonadaptive urban evolution to evaluate the support for each of these urban fragmentation and facilitation models. In a review of the literature with supporting quantitative analyses of 167 published urban population genetics studies, we found a weak signature of reduced within‐population genetic diversity and no evidence of consistently increased between‐population genetic differentiation associated with urbanization. In addition, we found that urban landscape features act as barriers or conduits to gene flow, depending on the species and city in question. Thus, we speculate that dispersal ability of species and environmental heterogeneity between cities contributes to the variation exhibited in our results. However, >90% of published studies reviewed here showed an association of urbanization with genetic drift or gene flow, highlighting the strong impact of urbanization on nonadaptive evolution. It is clear that species biology and city heterogeneity obscure patterns of genetic drift and gene flow in a quantitative analysis. Thus, we suggest that future research makes comparisons of multiple cities and nonurban habitats, and takes into consideration species' natural history, environmental variation, spatial modelling and marker selection.     

Rethinking Hardy-Weinberg and genetic drift in undergraduate biology

Population genetics is often taught in introductory biology classes, starting with the Hardy-Weinberg principle (HWP) and genetic drift. Here I argue that teaching these two topics first aligns neither with current expert knowledge, nor with good pedagogy. Student difficulties with mathematics in general, and probability in particular, make population genetics difficult to teach and learn. I recommend an alternative, historically inspired ordering of population genetics topics, based on progressively increasing mathematical difficulty. This progression can facilitate just-in-time math instruction. This alternative ordering includes, but does not privilege, the HWP and genetic drift. Stochastic events whose consequences are felt within a single generation, and the deterministic accumulation of the effects of selection across multiple generations, are both taught before tackling the stochastic accumulation of the effects of accidents of sampling.     

Reproductive compensation and human genetic disease

The effects of reproductive compensation on the population genetics of sex-linked recessive lethal mutations are investigated. Simple equations are presented which describe these effects, and so complement existing population genetic theory. More importantly, this type of mutation is responsible for several severe human genetic diseases such as Duchenne muscular dystrophy. It is argued that the applications of three modern reproductive technologies--effective family planning, in utero diagnosis with termination, and embryo sexing--will lead to reproductive compensation. The adoption of any of these technologies may rapidly elevate the frequencies of those mutations which are lethal in childhood. This increase is large, in the order of 33% upwards, and occurs rapidly over two to five generations. It also depends on the source of mutations, the effect being larger if most mutations are paternal. In utero diagnosis and/or embryo sexing increase the frequency of the mutation, but simultaneously decrease disease incidence by preventing the birth of affected offspring. In contrast, effective family planning may rapidly increase both mutation frequency and disease incidence.     

Exact compensation of stream drift as an evolutionarily stable strategy

The colonization cycle hypothesis predicts that adults of stream-dwelling insects preferentially disperse in the upstream direction in order to compensate for larval drift. Upstream biased dispersal has indeed been shown in many, albeit not all, natural populations. Based on a recently published analysis, we develop a simple stochastic model for the competition of genotypes with different dispersal strategies in a stream habitat. By means of an invasion analysis, we show that exact compensation of larval drift by upstream biased adult dispersal is an evolutionarily stable strategy. Exact compensation means that, on average, the net movement of individuals from birth to the time of reproduction is zero. At the population level, we show that, in general, upstream biased dispersal is not necessary for persistence, unless the reproductive rate is very low. Under all conditions, however, populations of exact compensators attain highest sizes or persistence times, respectively. Although selection pressure towards exact compensation is arguably very general in populations subject to stream drift, trade-offs or constraints might change the outcome of selection. Therefore, the analysis presented in this paper has to be viewed as a null model for optimal dispersal behavior in stream habitats.     

Generalized population models and the nature of genetic drift

The Wright–Fisher model of allele dynamics forms the basis for most theoretical and applied research in population genetics. Our understanding of genetic drift, and its role in suppressing the deterministic forces of Darwinian selection has relied on the specific form of sampling inherent to the Wright–Fisher model and its diffusion limit. Here we introduce and analyze a broad class of forward-time population models that share the same mean and variance as the Wright–Fisher model, but may otherwise differ. The proposed class unifies and further generalizes a number of population-genetic processes of recent interest, including the Λ and Cannings processes. Even though these models all have the same variance effective population size, they encode a rich diversity of alternative forms of genetic drift, with significant consequences for allele dynamics. We characterize in detail the behavior of standard population-genetic quantities across this family of generalized models. Some quantities, such as heterozygosity, remain unchanged; but others, such as neutral absorption times and fixation probabilities under selection, deviate by orders of magnitude from the Wright–Fisher model. We show that generalized population models can produce startling phenomena that differ qualitatively from classical behavior — such as assured fixation of a new mutant despite the presence of genetic drift. We derive the forward-time continuum limits of the generalized processes, analogous to Kimura’s diffusion limit of the Wright–Fisher process, and we discuss their relationships to the Kingman and non-Kingman coalescents. Finally, we demonstrate that some non-diffusive, generalized models are more likely, in certain respects, than the Wright–Fisher model itself, given empirical data from Drosophila populations.     

Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes

Dosage compensation in mammals involves silencing of one X chromosome in XX females and requires expression, in cis, of Xist RNA. The X to be inactivated is randomly chosen in cells of the inner cell mass (ICM) at the blastocyst stage of development. Embryonic stem (ES) cells derived from the ICM of female mice have two active X chromosomes, one of which is inactivated as the cells differentiate in culture, providing a powerful model system to study the dynamics of X inactivation. Using microarrays to assay expression of X-linked genes in undifferentiated female and male mouse ES cells, we detect global up-regulation of expression (1.4- to 1.6-fold) from the active X chromosomes, relative to autosomes. We show a similar up-regulation in ICM from male blastocysts grown in culture. In male ES cells, up-regulation reaches 2-fold after 2–3 weeks of differentiation, thereby balancing expression between the single X and the diploid autosomes. We show that silencing of X-linked genes in female ES cells occurs on a gene-by-gene basis throughout differentiation, with some genes inactivating early, others late, and some escaping altogether. Surprisingly, by allele-specific analysis in hybrid ES cells, we also identified a subgroup of genes that are silenced in undifferentiated cells. We propose that X-linked genes are silenced in female ES cells by spreading of Xist RNA through the X chromosome territory as the cells differentiate, with silencing times for individual genes dependent on their proximity to the Xist locus.     

Effects of headwater impoundment and channelization on invertebrate drift

The construction of a flood control impoundment on Twitty's Creek added large numbers of organisms of limnetic origin to the stream ecosystem. However, the number of limnetic organisms per unit volume of water decreased rapidly as the distance downstream from the reservoir increased and, during most sampling periods, made up an insignificant portion of the total drift biomass at 7.2 km downstream. Factors favoring the extended downstream drift of limnetic organisms were high stream discharge and low water temperature.Several taxa of benthic organisms had much lower drift rates in the station immediately below the dam than at other stations and several taxa commonly taken at other stations were not captured immediately below the reservoir outfall. One possible explanation is that these organisms may have longer drift recruitment distances than the distance from the reservoir outfall to the sample location.A comparison of drift densities of organisms of benthic origin and benthic standing crop densities in channeled and unchanneled streams revealed that drift densities were higher in channeled streams than in unchanneled streams for most taxa of invertebrates. In addition, channeled streams appeared to have lower benthic standing crops than unchanneled streams for most taxa of invertebrates.In stream sections impacted by either channelization or the Twitty Lake outfall, the energy dynamics of the stream ecosystems were altered by increased density of drifting invertebrates. From the standpoint of increasing food availability to the fish fauna of the stream, these changes would appear to benefit drift feeding species and negatively impact bottom feeding species.     

The impact of habitat loss and fragmentation on genetic drift and fixation time

In this study, a simple genetic model is integrated with an established method from landscape ecology to investigate the effect of habitat geometry and availability on genetic drift. Previous ecological modelling has identified a sharp threshold in habitat availability for species' persistence, beyond which the species rapidly becomes extinct. This study demonstrates the existence of a similar threshold for fixation time of selectively neutral genotypes by genetic drift, the location of which is determined by habitat shape and spatial correlation of habitat loss. Time to fixation is greater for habitats if they are long and thin rather than square. Despite reductions in population size due to habitat loss, fixation time remains relatively constant until a pre-threshold value, beyond which there is often a substantial increase in time to fixation. Further habitat loss results in the percolation threshold being reached and beyond this point the time to fixation decreases very rapidly. This study reveals a complex relationship between habitat availability, habitat geometry and the process of genetic drift. Possible implications of our results for conservation are discussed. Further work is required to improve our understanding of the interaction between evolutionary, ecological and landscape processes.     

Three components of genetic drift in subdivided populations

Wright's metaphor of sampling is extended to consider three components of genetic drift: those occurring before, during, and after migration. To the extent that drift at each stage behaves like an independent random sample, the order of events does not matter. When sampling is not random, the order does matter, and the effect of population size is confounded with that of mobility. The widely cited result that genetic differentiation of local groups depends only on the product of group size and migration rate holds only when nonrandom sampling does not occur prior to migration in the life cycle.     

Unbiased estimator for genetic drift and effective population size

Amounts of genetic drift and the effective size of populations can be estimated from observed temporal shifts in sample allele frequencies. Bias in this so-called temporal method has been noted in cases of small sample sizes and when allele frequencies are highly skewed. We characterize bias in commonly applied estimators under different sampling plans and propose an alternative estimator for genetic drift and effective size that weights alleles differently. Numerical evaluations of exact probability distributions and computer simulations verify that this new estimator yields unbiased estimates also when based on a modest number of alleles and loci. At the cost of a larger standard deviation, it thus eliminates the bias associated with earlier estimators. The new estimator should be particularly useful for microsatellite loci and panels of SNPs, representing a large number of alleles, many of which will occur at low frequencies.