R. C. Woodruff

Clusters of identical new mutation in the evolutionary landscape

In contrast to the common assumption that each new mutant results from a unique, independent mutation event, clusters of identical premeiotic mutant alleles are common. Clusters can produce large numbers of related individuals carrying identical copies of the same new genetic change. By entering the gene pool in multiple copies at one time, clusters can influence fundamental processes of population genetics. Here we report evidence that clusters can increase the arrival and fixation probabilities and can lengthen the average time to extinction of new mutations. We also suggest it may be necessary to reconsider other fundamental elements of population genetic theory.

Origin and decay of the P element-associated latitudinal cline in Australian Drosophila melanogaster

The latitudinal cline in P transposable element-associated characteristics in eastern Australian populations of Drosophila melanogaster has changed between 1986 and 1991–1994. New collections were made in 1991–1994 from localities along the eastern coast of Australia. P element-associated properties of 256 isofemale lines from 43 localities were evaluated using gonadal dysgenesis and/or singed-weak hypermutability assays. The overall results indicate that both P activity and P susceptibility have declined, with all populations showing a tendency towards a state with little P activity potential but with P repressor function (neutral or ‘Q’). P repressor function is strong in all populations except some of the most southerly. P activity potential peaks at about 27° SLat, and drops off to the south (as in 1983–1986 collections) and to the north (in contrast to 1983–1986 collections); thus the cline is no longer a simple P-to-Q-to-M pattern from north to south, but is now Q-P-Q-M. A mtDNA RFLP that putatively distinguishes North American and European populations varies in frequency among the populations but the frequency does not vary clinally with latitude, ruling out massive introductions from North America and Europe as causing the cline.

Genomic P elements and P-M characteristics of eastern Australian populations of Drosophila melanogaster

As part of our effort to monitor changes in the clinal pattern of P element-associated traits in eastern Australian Drosophila melanogaster, we investigated the genomic P elements of 293 isofemale lines collected in the period 1991–1994 from 45 localities. P elements were present in many copies in all genomes examined, with full-size P and KP element size classes accounting for the large majority. SR elements were not present in at least 92% of the lines tested. South of about 26° south Latitude (°SLat), the ratio of KP to full-size P elements (KP/P ratio) increased, correlating weakly with the P-M phenotypes of the populations, from moderately P populations (26–29°SLat) to M populations (37–38°SLat) North of 26°SLat, in weak P populations, the KP/P ratio was higher than between 26 and 29°Slat. The KP/P ratio appears to be higher in the northern populations than it was when previous studies were done. Overall, a high KP/P ratio among lines correlated roughly with a lack of P activity, but it also correlated with reduced repressor function. In a sample of 30 lines, a maternal effect of repressor function did not show a pattern with latitude, nor with KP/P ratio, nor with presence or absence of P activity.

Mutation rate: A simple concept has become complex

The factors that cause new mutations or affect the rate at which they occur have important implications for many areas of genetics. But recent work on phenomena such as premeiotic mutations, which yield a cluster of identical new mutants at the same time, led us to realize that researchers are using the term “mutation rate” in different, and sometimes contradictory, ways. One premeiotic genetic change may ultimately yield several new mutant offspring, but should this be considered one new mutation or many? The way the data are handled in analyses can have a significant effect on the results. How, then, does one handle clusters in the estimation of mutation rates? We explore this question and propose that geneticists begin to distinguish clearly between three different phenomena that to this point have been given the same name: the initial prerepair “genetic damage rate,” the postrepair “mutational event rate,” and the observed “mutation rate” as it is expressed in the proportion of new mutant offspring. We believe that all new mutant offspring should be counted when estimating mutation rate, irrespective of when in the developmental cycle it is believed that the initial mutational event occurred. Environ. Mol. Mutagen. 32: 292–300, 1998

Variation in spontaneous mutation and repair in natural population lines of Drosophila melanogaster

SummaryTo measure the possible correlation between genetic damage and repair ability in natural populations of a eukaryote, we compared the spontaneous frequency of sex-linked recessive lethal mutations and male recombination, which is associated with DNA transposable element induced chromosome breakage, with DNA repair efficiency in isofemale lines of a winery population of Drosophila melanogaster from Australia. Repair efficiency was measured by maternal effects on ring-X chromosome loss. Significant amounts of genetic variability for spontaneous rates of genetic change and for repair ability were observed in the isofemale lines collected during periods of low and high population density. However, there were no correlations between repair ability and rates of genetic damage. Possible reasons for the absence of correlation are discussed, along with the observations that: (a) the frequency of lethal mutations and ring-X chromosome losses were significantly higher in the small, resident population; (b) the rates of ring chromosome losses and especially lethal mutations are uniform over periods of time; (c) and inbreeding of isofemale lines leads to a reduction of the high spontaneous mutation rates.

Polygenic analysis of pattern formation: Interdependence among veins in the same compartment of the Drosophila wing

Polygenic modifiers of the L4 and L5 wing veins in Drosophila simulans were used to study the degree of genetic independence of veins within the same developmental compartment. The L4 and L5 were selected for opposite changes in length. Whole-chromosome assays of heterozygous effects showed that the L4 and L5 polygenic modifiers were associated with differences both in chromosomes and in interchromosomal interactions. A comparison of selection responses confirmed that, though some modifiers had strictly vein-specific action, others acted either upon all veins within the posterior compartment or upon all veins in the wing. The results support the idea that some genes control pattern formation in the wing as a whole, others regulate structures within a single compartment, and still others are limited to a single element within a compartment.

Intron retention in the Drosophila melanogaster Rieske iron sulphur protein gene generated a new protein

Genomes can encode a variety of proteins with unrelated architectures and activities. It is known that protein-coding genes of de novo origin have significantly contributed to this diversity. However, the molecular mechanisms and evolutionary processes behind these originations are still poorly understood. Here we show that the last 102 codons of a novel gene, Noble, assembled directly from non-coding DNA following an intronic deletion that induced alternative intron retention at the Drosophila melanogaster Rieske Iron Sulphur Protein (RFeSP) locus. A systematic analysis of the evolutionary processes behind the origin of Noble showed that its emergence was strongly biased by natural selection on and around the RFeSP locus. Noble mRNA is shown to encode a bona fide protein that lacks an iron sulphur domain and localizes to mitochondria. Together, these results demonstrate the generation of a novel protein at a naturally selected site.

Deleterious genomic mutation rate for viability in Drosophila melanogaster using concomitant sibling controls.

New deleterious mutations may reduce health and fitness and are involved in the evolution and maintenance of numerous biological processes. Hence, it is important to estimate the deleterious genomic mutation rate (U) in representative higher organisms. However, these estimated rates vary widely, mainly because of inadequate experimental controls. Here we describe an experimental design (the Binscy assay) with concomitant sibling controls and estimate U for viability in Drosophila melanogaster to be 0.31. This estimate, like most published studies, focuses on viability mutations and the overall deleterious genomic mutation rate would therefore be higher.

Mutation and evolution

Deleterious mutations.- Some evolutionary consequences of deleterious mutations.- Risk of population extinction from fixation of deleterious and reverse mutations.- Deleterious mutation accumulation in organelle genomes.- Mutation-selection balance with multiple alleles.- Mutation pressure, natural selection, and the evolution of base composition in Drosophila.- Deleterious mutations in animal mitochondrial DNA.- Requisite mutational load, pathway epistasis, and deterministic mutation accumulation in sexual versus asexual populations.- Neutral (nearly neutral) mutations.- Evolution by nearly-neutral mutations.- Compensatory neutral mutations and the evolution of RNA.- The amount and pattern of DNA polymorphism under the neutral mutation hypothesis.- Beneficial mutations.- Adaptive mutagenesis: a process that generates almost exclusively beneficial mutations.- The fate of competing beneficial mutations in an asexual population.- An embarrassment of riches: the stochastic generation of beneficial mutations.- Selection, convergence, and intragenic recombination in HLA diversity.- Quantitative traits.- Mutation and conflicts between artificial and natural selection for quantitative traits.- Measuring spontaneous deleterious mutation process.- Polygenic mutation in Drosophila melanogaster: genotype x environment interaction for spontaneous mutations affecting bristle number.- Environment-influenced expression of polygene mutations isolated from a natural population of Drosophila melanogaster.- Inferences on genome-wide deleterious mutation rates in inbred populations of Drosophila and mice.- How should we explain variation in the genetic variance of traits?.- The mutation rate and the distribution of mutational effects of viability and fitness in Drosophila melanogaster.- Evolution of intermediate self ing rates in plants: pollination ecology versus deleterious mutations.- Mathematical properties of mutation-selection models.- Mutation, life history, and senescence.- Mutation and senescence: where genetics and demography meet.- Spontaneous mutation for life-history traits in Drosophila melanogaster.- Mutation rates in mangroves and other plants.- Genetic changes.- Asymmetrical DNA replication promotes evolution: disparity theory of evolution.- Distribution of fitness effects caused by random insertion mutations in Escherichia coli.- Mutation and evolution of microsatellites in Drosophila melanogaster.- The molecular clock revisited: the rate of synonymous vs. replacement change in Drosophila.- Directional mutational pressure affects the amino acid composition and hydrophobicity of proteins in bacteria.- Mutation and selection at silent and replacement sites in the evolution of animal mitochondrial DNA.- Enigma of Y chromosome degeneration: Neo-Y and Neo-X chromosomes of Drosophila miranda a model for sex chromosome evolution.- Cell lineage selection, germinal mosaics, and evolution.- The developmental basis for germline mosaicism in mouse and Drosophila melanogaster.- Major impacts of gonadal mosaicism on hereditary risk estimation, origin of hereditary diseases, and evolution.- Discovery of numerous clusters of spontaneous mutations in the specific-locus test in mice necessitates major increases in estimates of doubling doses.- Clusters of new identical mutants and the fate of underdominant mutations.- Mutation and selection within the individual.- Mutation and the dynamics of adaptation.- Towards a theory of evolutionary adaptation.- A pleiotropic model of phenotypic evolution.- Population differentiation through mutation and drift - a comparison of genetic identity measures.- Inferring the major genomic mode of dominance and overdominance.- Genetic measurement theory of epistatic effects.

Highly variable recessive lethal or nearly lethal mutation rates during germ-line development of male Drosophila melanogaster

Each cell of higher organism adults is derived from a fertilized egg through a series of divisions, during which mutations can occur. Both the rate and timing of mutations can have profound impacts on both the individual and the population, because mutations that occur at early cell divisions will affect more tissues and are more likely to be transferred to the next generation. Using large-scale multigeneration screening experiments for recessive lethal or nearly lethal mutations of Drosophila melanogaster and recently developed statistical analysis, we show for male D. melanogaster that (i) mutation rates (for recessive lethal or nearly lethal) are highly variable during germ cell development; (ii) first cell cleavage has the highest mutation rate, which drops substantially in the second cleavage or the next few cleavages; (iii) the intermediate stages, after a few cleavages to right before spermatogenesis, have at least an order of magnitude smaller mutation rate; and (iv) spermatogenesis also harbors a fairly high mutation rate. Because germ-line lineage shares some (early) cell divisions with somatic cell lineage, the first conclusion is readily extended to a somatic cell lineage. It is conceivable that the first conclusion is true for most (if not all) higher organisms, whereas the other three conclusions are widely applicable, although the extent may differ from species to species. Therefore, conclusions or analyses that are based on equal mutation rates during development should be taken with caution. Furthermore, the statistical approach developed can be adopted for studying other organisms, including the human germ-line or somatic mutational patterns.