Abstract Spontaneous mutation to mildly deleterious alleles has emerged as a potentially unifying component of a variety of observations in evolutionary genetics and molecular evolution. However, the biological significance of hypotheses based on mildly deleterious mutation depends critically on the rate at which new mutations arise and on their average effects. A long-term mutation-accumulation experiment with replicate lines of the nematode Caenorhabditis elegans maintained by single-progeny descent indicates that recurrent spontaneous mutation causes approximately 0.1% decline in fitness per generation, which is about an order of magnitude less than that suggested by previous studies with Drosophila. Two rather different approaches, Bateman-Mukai and maximum likelihood, suggest that this observation, along with the observed rate of increase in the variance of fitness among lines, is consistent with a genomic deleterious mutation rate for fitness of approximately 0.03 per generation and with an average homozygous effect of approximately 12%. The distribution of mutational effects for fitness appears to have a relatively low coefficient of variation, being no more extreme than expected for a negative exponential, and for one composite fitness measure (total progeny production) approaches constancy of effects. These results are derived from assays in a benign environment. At stressful temperatures, estimates of the genomic deleterious mutation rate (for genes expressed at such temperatures) is sixfold lower, whereas those for the average homozygous effect is approximately eightfold higher. Our results are reasonably compatible with existing estimates for flies, when one considers the differences between these species in the number of germ-line cell divisions per generation and the magnitude of transposable element activity. Corresponding Editor: A. Caballero
Abstract While the genetic consequences of inbreeding and small population size are of fundamental importance in many areas of biology, empirical research on these phenomena has proceeded in the absence of a well-developed statistical methodology. The usual approach is to compare observed means and variances with the expectations of Wright's neutral, additive genetic model for quantitative characters. If the observations deviate from the expectations more than can be accounted for by sampling variance of the parameter estimates, the null hypothesis is routinely rejected in favor of alternatives invoking evolutionary forces such as selection or nonadditive gene action. This is a biased procedure because it treats sequential samples from the same populations as independent, and because it ignores the fact that the expectations of the neutral additive genetic model will rarely be realized when only a finite number of lines are studied. Even when genes are perfectly additive and neutral, the variation among the properties of founder populations, the random development of linkage disequilibrium within lines, and the variance in inbreeding between lines reduce the likelihood that Wright's expectations will be realized in any particular set of lines. Under most experimental designs, these sources of variation are much too large to be ignored. Formulas are presented for the variance-covariance structure of the realized within- and between-line variance under the neutral additive genetic model. These results are then used to develop statistical tests for detecting the operation of selection and/or inbreeding depression in small populations. A number of recommendations are made for the optimal design of experiments on drift and inbreeding, and a method is suggested for the correction of data for general environmental effects. In general, it appears that we can best understand the response of populations to inbreeding and finite population size by studying a very large number (>100) of self-fertilizing or full-sib mated lines in parallel with one or more stable control populations.
This paper discusses materials from a legal case, People v. Hyatt (2001). This was a criminal case in which one of the authors (Simon Cole) agreed to appear as an expert witness for the defense. Cole's expertise derived from his research in the field of Science and Technology Studies (STS), and so his appearance in the case exemplified STS research engaging in a public controversy about a contested form of 'scientific' knowledge. Cole's STS work and his testimony proved useful to defendants seeking to restrict the admissibility of forensic fingerprint evidence in court, but before he could testify in the Hyatt trial, his own expertise was subjected to an admissibility hearing. During his testimony, Cole faced a number of dilemmas as he attempted to accommodate his own conception of science and STS with the terms and procedures recognized by the court. The hearing was transcribed, and the co-authors of this paper discussed the details of the transcript. Their discussion itself was recorded and transcribed, and portions of the two transcripts are juxtaposed in this paper. The paper discusses Cole's difficulties and the dilemmas they exemplify, as a situated demonstration of some of the difficulties STS scholars face in their attempts to engage the 'public sphere'.
Abstract A tolerance curve defines the dependence of a genotype's fitness on the state of an environmental gradient. It can be characterized by a mode (the genotype's optimal environment) and a width (the breadth of adaptation). It seems possible that one or both of these characters can be modified in an adaptive manner, at least partially, during development. Thus, we extend the theory of environmental tolerance to include reaction norms for the mode and the width of the tolerance curve. We demonstrate that the selective value of such reaction norms increases with increasing spatial heterogeneity and between‐generation temporal variation in the environment and with decreasing within‐generation temporal variation. Assuming that the maintenance of a high breadth of adaptation is costly, reaction, norms are shown to induce correlated selection for a reduction in this character. Nevertheless, regardless of the magnitude of the reaction norm, there is a nearly one to one relationship between the optimal breadth of adaptation and the within‐generation temporal variation perceived by the organism. This suggests that empirical estimates of the breadth of adaptation may provide a useful index of this type of environmental variation from the organism's point of view.
The Sm family of proteins is closely associated with RNA metabolism throughout all life. These proteins form homomorphic and heteromorphic rings consisting of six or seven subunits with a characteristic central pore, the presence of which is critical for binding U-rich regions of single-stranded RNA. Eubacteria and Archaea typically carry one or two forms of Sm proteins and assemble one homomorphic ring per Sm protein. Eukaryotes typically carry 16 or more Sm proteins that assemble to form heteromorphic rings which lie at the center of a number of critical RNA-associated small nuclear ribonucleoproteins (snRNPs). High Sm protein diversity and heteromorphic Sm rings are features stretching back to the origin of eukaryotes; very deep phylogenetic divisions among existing Sm proteins indicate simultaneous evolution across essentially all existing eukaryotic life. Two basic forms of heteromorphic Sm rings are found in eukaryotes. Fixed Sm rings are highly stable and static and are assembled around an RNA cofactor. Flexible Sm rings also stabilize and chaperone RNA but assemble in the absence of an RNA substrate and, more significantly, associate with and dissociate from RNA substrates more freely than fixed rings. This suggests that the conformation of flexible Sm rings might be modified in some specific manner to facilitate association and dissociation with RNA. Diversification of eukaryotic Sm proteins may have been initiated by gene transfers and/or genome clashes that accompanied the origin of the eukaryotic cell itself, with further diversification driven by a greater need for steric specificity within increasingly complex snRNPs.
The geographic structure of Daphnia pulex populations from the central United States is analyzed with respect to isozyme and mitochondrial DNA variation. The species complex consists of cyclic and obligate parthenogens. A hierarchical analysis of population structure in the cyclic parthenogens by using a fixation-index approach indicates that this is one of the most extremely subdivided species yet studied. This genetic structure, much of which accrues within 100 km, is certainly due in part to the limited dispersal ability of Daphnia. However, previous work has shown that fluctuating selection can account for the spatial heterogeneity in isozyme frequencies in these populations. This may explain why the population subdivision for the mitochondrial genome increases approximately three times as rapidly with distance as does that for nuclear genes, which is slower than the neutral expectation. The obligate parthenogens are shown to be polyphyletic in origin, evolutionarily young, and, in some cases, geographically widespread.
In an effort to elucidate the evolutionary mechanisms that determine the genetic architecture of a species, we have analyzed 17 populations of the microcrustacean Daphnia pulex for levels of genetic variation at the level of life-history characters and molecular markers in the nuclear and mitochondrial genomes. This species is highly subdivided, with approximately 30% of the variation for nuclear molecular markers and 50% of the variation for mitochondrial markers being distributed among populations. The average level of genetic subdivision for quantitative traits is essentially the same as that for nuclear markers, which superficially suggests that the life-history characters are diverging at the neutral rate. However, the existence of a strong correlation between the levels of population subdivision and broadsense heritabilities of individual traits argues against this interpretation, suggesting instead that the among-population divergence of some quantitative traits (most notably body size) is being driven by local adaptation to different environments. The fact that the mean phenotypes of the individual populations are also strongly correlated with local levels of homozygosity indicates that variation in local inbreeding plays a role in population differentiation. Rather than being a passive consequence of local founder effects, levels of homozygosity may be selected for directly for their effects on the phenotype (adaptive inbreeding depression). There is no relationship between the levels of variation within populations for molecular markers and quantitative characters, and this is explained by the fact that the average standing genetic variation for life-history characters in this species is equivalent to only 33 generations of variation generated by mutation.
Index entries from the subject indexes to CA can, in general, be converted to ‘normal’ or title‐like phrases by applying simple tests to the positions of prepositions and conjunctions in the entries. Other, more complex, entries can be transformed after somewhat deeper analysis. These manipulations are a necessary preliminary step to the use of the subject‐index language in retrieval. A scheme is outlined for automatically compiling and editing subject indexes by transforming descriptive phrases with regular structure and vocabulary. These transformations, based on the formal structure of language, are shown to be admirably suited to computer manipulation.
All life forms depend on the conversion of energy into biomass used in growth and reproduction. For unicellular heterotrophs, the energetic cost associated with building a cell scales slightly sublinearly with cell weight. However, observations on multiple Daphnia species and numerous other metazoans suggest that although a similar size-specific scaling is retained in multicellular heterotrophs, there is a quantum leap in the energy required to build a replacement soma, presumably owing to the added investment in nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport. Thus, any context-dependent ecological advantages that accompany the evolution of multicellularity come at a high baseline bioenergetic cost. At the phylogenetic level, for both unicellular and multicellular eukaryotes, the energetic expense per unit biomass produced declines with increasing adult size of a species, but there is a countergradient scaling within the developmental trajectories of individual metazoan species, with the cost of biomass production increasing with size. Translation of the results into the universal currency of adenosine triphosphate (ATP) hydrolyses provides insight into the demands on the electron-transport/ATP-synthase machinery per organism and on the minimum doubling times for biomass production imposed by the costs of duplicating the energy-producing infrastructure.
Abstract The molecular mechanisms leading to asexuality remain little understood despite their substantial bearing on why sexual reproduction is dominant in nature. Here, we examine the role of hybridization in the origin and spread of obligate asexuality in D aphnia pulex , arguably the best‐documented case of contagious asexuality. Obligately parthenogenetic ( OP ) clones of D. pulex have traditionally been separated into ‘hybrid’ ( Ldh SF ) and ‘nonhybrid’ ( Ldh SS ) forms because the lactase dehydrogenase ( Ldh ) locus distinguishes the cyclically parthenogenetic ( CP ) lake dwelling D aphnia pulicaria ( Ldh FF ) from its ephemeral pond dwelling sister species D . pulex ( Ldh SS ). The results of our population genetic analyses based on microsatellite loci suggest that both Ldh SS and SF OP individuals can originate from the crossing of CP female F 1 ( D . pulex × D . pulicaria ) and backcross with males from OP lineages carrying genes that suppress meiosis specifically in female offspring. In previous studies, a suite of diagnostic markers was found to be associated with OP in Ldh SS D . pulex lineages. Our association mapping supports a similar genetic mechanism for the spread of obligate parthenogenesis in Ldh SF OP individuals. Interestingly, our study shows that CP D . pulicaria carry many of the diagnostic microsatellite alleles associated with obligate parthenogenesis. We argue that the assemblage of mutations that suppress meiosis and underlie obligate parthenogenesis in D . pulex originated due to a unique historical hybridization and introgression event between D . pulex and D . pulicaria .
Abstract Using data from 83 isolates from a single population, the population genomics of the microcrustacean Daphnia pulex are described and compared to current knowledge for the only other well-studied invertebrate, Drosophila melanogaster. These two species are quite similar with respect to effective population sizes and mutation rates, although some features of recombination appear to be different, with linkage disequilibrium being elevated at short (<100 bp) distances in D. melanogaster and at long distances in D. pulex. The study population adheres closely to the expectations under Hardy–Weinberg equilibrium, and reflects a past population history of no more than a twofold range of variation in effective population size. Fourfold redundant silent sites and a restricted region of intronic sites appear to evolve in a nearly neutral fashion, providing a powerful tool for population genetic analyses. Amino acid replacement sites are predominantly under strong purifying selection, as are a large fraction of sites in UTRs and intergenic regions, but the majority of SNPs at such sites that rise to frequencies >0.05 appear to evolve in a nearly neutral fashion. All forms of genomic sites (including replacement sites within codons, and intergenic and UTR regions) appear to be experiencing an ∼2× higher level of selection scaled to the power of drift in D. melanogaster, but this may in part be a consequence of recent demographic changes. These results establish D. pulex as an excellent system for future work on the evolutionary genomics of natural populations.
Variation in the ribosomal DNA (rDNA) gene family was surveyed in five cyclically parthenogenetic populations of Daphnia pulex from central Illinois and in obligately parthenogenetic clones from Illinois and Ontario.A total of 37 distinct rDNA repeat types were identified on the basis of restriction-site and repeat-length polymorphism in a sample of 90 isolates.Repeat-type diversity was high within cyclic populations; however, individuals possessed only a small subset of the repeat-type variation present in each population.The distribution of repeat types within and among individuals suggested that new variants spread within rDNA arrays much faster than arrays carrying the variants spread within populations.This observation is contrary to a model developed by Ohta and Dover for strictly sexual organisms.Previous surveys of isozyme and mitochondrial DNA variation in these populations showed that gene flow among them is limited.Hierarchical analysis of rDNA restriction-site variation was consistent with this observation and showed that genetic divergence accumulates between populations for rDNA almost as rapidly as it does for single-copy nuclear genes (isozymes).Analysis of rDNA variation in obligately parthenogenetic clones provided evidence that both intra-and interchromosomal exchanges occur between rDNA arrays in the absence of meiosis.Moreover, individuals reproducing by obligate parthenogenesis possessed fewer rDNA repeat types, on average, than did individuals from cyclic populations, suggesting that there is a net loss of rDNA repeat-type variability within obligately clonal lineages over time.Preliminary analyses of two additional species, D. pulicaria and D. obtusa, revealed several restriction-site polymorphisms that were found in more than one of the three species.The existence of such shared polymorphisms advises caution in the use of multigene-family variation to infer phylogenies among species when levels of intraspecific variation have not been assessed.1.
Abstract Spontaneous mutations are ultimately essential for evolutionary change and are also the root cause of many diseases. However, until recently, both biological and technical barriers have prevented detailed analyses of mutation profiles, constraining our understanding of the mutation process to a few model organisms and leaving major gaps in our understanding of the role of genome content and structure on mutation. Here, we present a genome-wide view of the molecular mutation spectrum in Burkholderia cenocepacia, a clinically relevant pathogen with high %GC content and multiple chromosomes. We find that B. cenocepacia has low genome-wide mutation rates with insertion–deletion mutations biased toward deletions, consistent with the idea that deletion pressure reduces prokaryotic genome sizes. Unlike prior studies of other organisms, mutations in B. cenocepacia are not AT biased, which suggests that at least some genomes with high %GC content experience unusual base-substitution mutation pressure. Importantly, we also observe variation in both the rates and spectra of mutations among chromosomes and elevated G:C > T:A transversions in late-replicating regions. Thus, although some patterns of mutation appear to be highly conserved across cellular life, others vary between species and even between chromosomes of the same species, potentially influencing the evolution of nucleotide composition and genome architecture.
