Evolution of behavior by density-dependent natural selection.

Theories of density-dependent natural selection predict that evolution should favor those genotypes with the highest per capita rates of population growth under the current density conditions. These theories are silent about the mechanisms that may give rise to these increases in density-dependent growth rates. We have observed the evolution of six populations of Drosophila melanogaster recently placed in crowded environments after nearly 200 generations at low-population density in the laboratory. After 25 generations in these crowded cultures all six populations showed the predicted increase in population growth rates at high-population density with the concomitant decrease in their growth rates at low densities. These changes in rates of population growth are accompanied by changes in the feeding and pupation behavior of the larvae: those populations that have evolved at high-population densities have higher feeding rates and are less likely to pupate on or near the food surface than populations maintained at low densities. These changes in behavior serve to increase the competitive ability of larvae for limited food and reduce mortality under crowded conditions during the pupal stage of development. A detailed understanding of the mechanisms by which populations evolve under density-dependent natural selection will provide a framework for understanding the nature of trade-offs in life history evolution.     

Density-dependent selection in a random environment: An evolutionary process that can maintain stable population dynamics

A theoretical analysis of natural selection is presented in which fitnesses depend on population density and randomly varying environmental processes. The theory is based on a general, heuristic analysis of a pair of coupled, nonlinear, stochastic difference equations that describe the joint dynamics of allele frequencies and population size. Four main conclusions emerge from the investigation of a particular class of models: (i) growth rates at low population densities tend to increase; (ii) individual selection, given sufficient genetic flexibility, will mold growth rates at higher densities so that in spite of i, stable deterministic population dynamics are maintained; (iii) “more fit” genotypes cannot be simply characterized—in particular, the mean population size need not be increased; and (iv) genetic polymorphisms can be maintained in both haploid and diploid organisms.     

Boundary-layer model for the population dynamics of single species

We develop a new discrete-time model, called the boundary-layer model, to describe the dynamics of single species that have a capacity for fast growth at very low population densities. The model explicitly separates the dynamics of the population at very low densities (within the “boundary layer”) and at high densities. The boundary-layer model provides a better fit than other models such as the logistic or the θ model to data from experimental populations of Drosophila willistoni and D. pseudoobscura.     

Evolution of foraging behavior in Drosophila by density-dependent selection

One of the rare examples of a single major gene underlying a naturally occurring behavioral polymorphism is the foraging locus of Drosophila melanogaster. Larvae with the rover allele, for^R, have significantly longer foraging path lengths on a yeast paste than do those homozygous for the sitter allele, for^s. These variants do not differ in general activity in the absence of food. The evolutionary significance of this polymorphism is not as yet understood. Here we examine the effect of high and low animal rearing densities on the larval foraging path-length phenotype and show that density-dependent natural selection produces changes in this trait. In three unrelated base populations the long path (rover) phenotype was selected for under high-density rearing conditions, whereas the short path (sitter) phenotype was selected for under low-density conditions. Genetic crosses suggested that these changes resulted from alterations in the frequency of the for^s allele in the low-density-selected lines. Further experiments showed that density-dependent selection during the larval stage rather than the adult stage of development was sufficient to explain these results. Density-dependent mechanisms may be sufficient to maintain variation in rover and sitter behavior in laboratory populations.     

Loss of social behaviors by Myxococcus xanthus during evolution in an unstructured habitat

Social behaviors are often targets of natural selection among higher organisms, but quantifying the effects of such selection is difficult. We have used the bacterium Myxococcus xanthus as a model system for studying the evolution of social interactions. Changes in the social behaviors of 12 M. xanthus populations were quantified after 1,000 generations of evolution in a liquid habitat, in which interactions among individuals were continually hindered by shaking and low cell densities. Derived lineages were compared with their ancestors with respect to maximum growth rate, motility rates on hard and soft agar, fruiting body formation ability, and sporulation frequency during starvation. Improved performance in the liquid selective regime among evolved lines was usually associated with significant reductions in all of the major social behaviors of M. xanthus. Maintenance of functional social behaviors is apparently detrimental to fitness under asocial growth conditions.     

A demographic approach to selection

The concepts of demography provide a means of combining the ecological approach to population growth with the genetical approach to natural selection. We have utilized the demographic theory of natural selection developed by Norton and Charlesworth to analyze life history schedules of births and deaths for populations of genotypes in Drosophila pseudoobscura. Our populations illustrate a stable genetic equilibrium, an unstable genetic equilibrium, and a case of no equilibrium. We have estimated population growth rates and Darwinian fitnesses of the genotypes and have explored the role of population growth in determining natural selection. The age-specific rates of births and deaths provide insights into components of selection. Both viability and fertility are important components in our populations.     

When does the good of the group override the advantage of the individual?

In a system of N populations of n reproductive individuals apiece, in which each population has constant variance v² and lasts L generations, group selection on a quantitative character has a reasonable chance of overriding selection within populations if (and only if) the populations never exchange migrants, each population is founded by colonists from a single parent population, and the number of populations exceeds the effective number of reproductive individuals per population. If each population derives from a single parent population, then the exchange of a single successful migrant per population per L generations can triple the strength of group selection required to overcome a given selection within populations. If populations exchange no migrants, then the derivation of one in every N populations from two equally represented parents (while the others all derive from a single parent) doubles the strength of group selection required to prevail. Group selection is accordingly likely to be effective only in certain categories of parasites.     

Extensive variation and heteroplasmy in size of mitochondrial DNA among geographic populations of Drosophila melanogaster

Size variation and heteroplasmy in mitochondrial DNA (mtDNA) are relatively common in natural populations of Drosophila melanogaster. Of 92 isofemale lines of flies obtained from various geographic regions throughout the world, 75 lines were homoplasmic and showed a total of 12 different mtDNA size classes. The remaining 17 lines were heteroplasmic, each line carrying two different mtDNAs, and, in all but one case, the mtDNAs in these heteroplasmic lines differed in size; a total of nine size classes was represented among them. In cases where one type was predominant within an individual, it was usually the smaller mtDNA. This finding parallels what was observed in homoplasmic lines, in that the smaller mtDNAs were much more common than the larger variants in most populations. The data suggest a high rate of mutational occurrence of mtDNA size variants and some natural selection against them.     

Rapid decline of fitness in panmictic populations of Drosophila melanogaster maintained under relaxed natural selection

The parameters of the spontaneous deleterious mutation process remain poorly known, despite their importance. Here, we report the results of a mutation accumulation experiment performed on panmictic populations of Drosophila melanogaster without any genetic manipulations. Two experimental populations were kept for 30 generations under relaxed natural selection. Each generation, 100 pairs were formed randomly, and every fecund pair contributed a son and a daughter to the next generation. Comparison with two controls, one cryopreserved and the other kept as the experimental populations but with long generation time, showed that the number of surviving offspring per female declined by 0.2% and 2.0% per generation under benign and harsh, competitive conditions, respectively. Thus, the mutational pressure on fitness may be strong and depends critically on the conditions under which fitness is assayed.     

Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression

Gene expression levels appear to be under pervasive stabilizing selection. Yet the genetic architecture underlying abundant gene expression diversity within and between populations remains elusive. Here, we investigated the role of dominance in the segregation of cis- and trans-regulation within and between populations. We used chromosome substitution lines of Drosophila melanogaster to show that (i) >70% of the genes that are differentially expressed between two homozygous lines are masked in the heterozygous, suggesting that one of the substituted chromosomes contains a recessive allele; (ii) such large masking is already obtained with heterozygous chromosomes originating from the same population, with the time of divergence between chromosomes in heterozygous lines making only a small but significant contribution to the masking of variation observed in homozygous lines; (iii) variation in gene expression due to trans-regulation is biased toward greater deviations from additivity because of recessive and dominant alleles, whereas variation due to cis-regulation shows higher additivity; and (iv) genetic divergence between second chromosomes is associated with increased cis-regulation, whereas the level of trans-regulation shows little increase over the time scale studied. Our results indicate that cis-acting alleles may be preferentially fixed by positive natural selection because of their higher additivity, and that the disruption of gene expression by recessive variation with pervasive trans-effects may be important for understanding gene expression variation within populations. We suggest that widespread regulatory effects of recessive low-frequency homozygous variation may provide a general mechanism mediating disease phenotypes and the genetic load of natural populations.     

Population oscillations and energy reserves in planktonic cladocera and their consequences to competition

Time lags in an individual's response to decreased food densities are responsible for oscillations in laboratory populations of Daphnia galeata mendotae. Visible energy reserves of triacylglycerols accumulate in the body of animals at low population densities when food is abundant and are later metabolized at high population densities when food is scarce to temporarily sustain activity and reproduction. After these energy reserves are metabolized many individuals, primarily juveniles, starve and die. The length of the time lags is a function of the amount of energy reserve accumulated in the individual. Because this sustained activity and reproduction further decreases food concentrations to very low levels, individuals of a second smaller-body-sized species, Bosmina longirostris, that do not have sufficient energy reserves quickly starve and die. Thus the accumulation of energy reserves in individuals underlies the time lags important in causing population oscillations and has consequences to interspecific competition.     

New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster

The genomic rate and distribution of effects of deleterious mutations are important parameters in evolutionary theory. The most detailed information comes from the work of Mukai and Ohnishi, who allowed mutations to accumulate on Drosophila melanogaster second chromosomes, shielded from selection and recombination by being maintained heterozygous in males. Averaged over studies, the estimated rate of nonlethal viability mutations per second chromosome per generation under an equal-effects model, U_BM, was 0.12, suggesting a high genomic mutation rate. We have performed a mutation-accumulation experiment similar to those of Mukai and Ohnishi, except that three large homozygous control populations were maintained. Egg-to-adult viability of 72 nonlethal mutation-accumulation (MA) lines and the controls was assayed after 27–33 generations of mutation accumulation. The rate of decline in mean viability was significantly lower than observed by Mukai, and the rate of increase in among-line variance was significantly higher. Our U_BM estimate of 0.02 is much lower than the previous estimates. Our results suggest that the rate of mutations that detectably reduce viability may not be much greater than the lethal mutation rate (0.01 in these lines), but the results also are consistent with models that include many mutations with very small effects.     

Gun Ownership and Firearm-related Deaths

Background

A variety of claims about possible associations between gun ownership rates, mental illness burden, and the risk of firearm-related deaths have been put forward. However, systematic data on this issue among various countries remain scant. Our objective was to assess whether the popular notion “guns make a nation safer” has any merits.

Methods

Data on gun ownership were obtained from the Small Arms Survey, and for firearm-related deaths from a European detailed mortality database (World Health Organization), the National Center for Health Statistics, and others. Crime rate was used as an indicator of safety of the nation and was obtained from the United Nations Surveys of Crime Trends. Age-standardized disability-adjusted life-year rates due to major depressive disorder per 100,000 inhabitants with data obtained from the World Health Organization database were used as a putative indicator for mental illness burden in a given country.

Results

Among the 27 developed countries, there was a significant positive correlation between guns per capita per country and the rate of firearm-related deaths (r = 0.80; P <.0001). In addition, there was a positive correlation (r = 0.52; P = .005) between mental illness burden in a country and firearm-related deaths. However, there was no significant correlation (P = .10) between guns per capita per country and crime rate (r = .33), or between mental illness and crime rate (r = 0.32; P = .11). In a linear regression model with firearm-related deaths as the dependent variable with gun ownership and mental illness as independent covariates, gun ownership was a significant predictor (P <.0001) of firearm-related deaths, whereas mental illness was of borderline significance (P = .05) only.

Conclusion

The number of guns per capita per country was a strong and independent predictor of firearm-related death in a given country, whereas the predictive power of the mental illness burden was of borderline significance in a multivariable model. Regardless of exact cause and effect, however, the current study debunks the widely quoted hypothesis that guns make a nation safer.     

Recent acceleration of human adaptive evolution

Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during the last 40,000 years. We tested the null hypothesis that the observed age distribution of recent positively selected linkage blocks is consistent with a constant rate of adaptive substitution during human evolution. We show that a constant rate high enough to explain the number of recently selected variants would predict (i) site heterozygosity at least 10-fold lower than is observed in humans, (ii) a strong relationship of heterozygosity and local recombination rate, which is not observed in humans, (iii) an implausibly high number of adaptive substitutions between humans and chimpanzees, and (iv) nearly 100 times the observed number of high-frequency linkage disequilibrium blocks. Larger populations generate more new selected mutations, and we show the consistency of the observed data with the historical pattern of human population growth. We consider human demographic growth to be linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of our species.     

Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans

Theory concerning the evolution of sex and recombination and mutation load relies on information on rates and distributions of effects of deleterious mutations. Direct information on the genomic mutation rate in Drosophila implies that an accumulation of mildly deleterious mutations reduces viability of populations by at least 1% per generation. We carried out an experiment to measure the deleterious mutation rate in Caenorhabditis elegans, in which independent sublines were maintained with one hermaphrodite parent per generation, conditions that minimize the opportunity for natural selection and lead to random fixation of deleterious mutations. After 60 generations of mutation accumulation, negligible changes in mean reproductive output and lifespan occurred, but the genetic variance increased at rates typical for life history traits in other species. The estimated deleterious mutation rate per haploid genome for fitness, U, was 0.0026, a figure two orders of magnitude smaller than previously measured for viability in Drosophila.     

Evolution of competitive ability in Drosophila by density-dependent natural selection.

The theory of density-dependent natural selection predicts that populations kept at extreme densities should evolve different competitive abilities for limited resources. These predictions have been tested with laboratory populations of Drosophila melanogaster. Six independent populations were maintained in two environments, called r and K, for 128 generations. In the r environment, population sizes were small and resources for larvae and adults were abundant. In contrast the populations in the K environment were large and crowded, and resources, such as food and space, were in short supply. The relative competitive ability for food has been estimated for each population. Populations from the K environment consume food at a rate that is 58% greater than the average rate for the r population. The differentiation of competitive abilities in these populations is due to natural selection and is consistent with predictions from the theory of evolutionary ecology.     

Allee effect promotes diversity in traveling waves of colonization

Most mathematical studies on expanding populations have focused on the rate of range expansion of a population. However, the genetic consequences of population expansion remain an understudied body of theory. Describing an expanding population as a traveling wave solution derived from a classical reaction-diffusion model, we analyze the spatio-temporal evolution of its genetic structure. We show that the presence of an Allee effect (i.e., a lower per capita growth rate at low densities) drastically modifies genetic diversity, both in the colonization front and behind it. With an Allee effect (i.e., pushed colonization waves), all of the genetic diversity of a population is conserved in the colonization front. In the absence of an Allee effect (i.e., pulled waves), only the furthest forward members of the initial population persist in the colonization front, indicating a strong erosion of the diversity in this population. These results counteract commonly held notions that the Allee effect generally has adverse consequences. Our study contributes new knowledge to the surfing phenomenon in continuous models without random genetic drift. It also provides insight into the dynamics of traveling wave solutions and leads to a new interpretation of the mathematical notions of pulled and pushed waves.     

Directionality principles in thermodynamics and evolution

Directionality in populations of replicating organisms can be parametrized in terms of a statistical concept: evolutionary entropy. This parameter, a measure of the variability in the age of reproducing individuals in a population, is isometric with the macroscopic variable body size. Evolutionary trends in entropy due to mutation and natural selection fall into patterns modulated by ecological and demographic constraints, which are delineated as follows: (i) density-dependent conditions (a unidirectional increase in evolutionary entropy), and (ii) density-independent conditions, (a) slow exponential growth (an increase in entropy); (b) rapid exponential growth, low degree of iteroparity (a decrease in entropy); and (c) rapid exponential growth, high degree of iteroparity (random, nondirectional change in entropy). Directionality in aggregates of inanimate matter can be parametrized in terms of the statistical concept, thermodynamic entropy, a measure of disorder. Directional trends in entropy in aggregates of matter fall into patterns determined by the nature of the adiabatic constraints, which are characterized as follows: (i) irreversible processes (an increase in thermodynamic entropy) and (ii) reversible processes (a constant value for entropy). This article analyzes the relation between the concepts that underlie the directionality principles in evolutionary biology and physical systems. For models of cellular populations, an analytic relation is derived between generation time, the average length of the cell cycle, and temperature. This correspondence between generation time, an evolutionary parameter, and temperature, a thermodynamic variable, is exploited to show that the increase in evolutionary entropy that characterizes population processes under density-dependent conditions represents a nonequilibrium analogue of the second law of thermodynamics.     

Analysis of natural variation reveals neurogenetic networks for Drosophila olfactory behavior

Understanding the relationship between genetic variation and phenotypic variation for quantitative traits is necessary for predicting responses to natural and artificial selection and disease risk in human populations, but is challenging because of large sample sizes required to detect and validate loci with small effects. Here, we used the inbred, sequenced, wild-derived lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to perform three complementary genome-wide association (GWA) studies for natural variation in olfactory behavior. The first GWA focused on single nucleotide polymorphisms (SNPs) associated with mean differences in olfactory behavior in the DGRP, the second was an extreme quantitative trait locus GWA on an outbred advanced intercross population derived from extreme DGRP lines, and the third was for SNPs affecting the variance among DGRP lines. No individual SNP in any analysis was associated with variation in olfactory behavior by using a strict threshold accounting for multiple tests, and no SNP overlapped among the analyses. However, combining the top SNPs from all three analyses revealed a statistically enriched network of genes involved in cellular signaling and neural development. We used mutational and gene expression analyses to validate both candidate genes and network connectivity at a high rate. The lack of replication between the GWA analyses, small marginal SNP effects, and convergence on common cellular networks were likely attributable to epistasis. These results suggest that fully understanding the genotype–phenotype relationship requires a paradigm shift from a focus on single SNPs to pathway associations.     

CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome

Thirty-six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+-selected peripheral blood progenitor cell transplantation (PBPCT) following high-dose melphalan alone or high-dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G-CSF). CD34+ selection using the Cellpro Ceprate-SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+-selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event-free survival (EFS) between the CD34+-selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+-selection process therefore reduced contamination but did not eliminate it completely, and in this small non-randomized study there was no apparent clinical benefit of CD34+ selection.