Bas J. Zwaan

Reduced insulin/IGF-1 signalling and human longevity

Evidence is accumulating that aging is hormonally regulated by an evolutionarily conserved insulin/IGF‐1 signalling (IIS) pathway. Mutations in IIS components affect lifespan in Caenorhabditis elegans, Drosophila melanogaster and mice. Most long‐lived IIS mutants also show increased resistance to oxidative stress. In D. melanogaster and mice, the long‐lived phenotype of several IIS mutants is restricted to females. Here, we analysed the relationship between IIS signalling, body height and longevity in humans in a prospective follow‐up study. Based on the expected effects (increased or decreased signalling) of the selected variants in IIS pathway components (GHRHR, GH1, IGF1, INS, IRS1), we calculated composite IIS scores to estimate IIS pathway activity. In addition, we analysed the relative impact on lifespan and body size of the separate variants in multivariate models. In women, lower IIS scores are significantly associated with lower body height and improved old age survival. Multivariate analyses showed that these results were most pronounced for the GH1 SNP, IGF1 CA repeat and IRS1 SNP. In females, for variant allele carriers of the GH1 SNP, body height was 2 cm lower (P = 0.007) and mortality 0.80‐fold reduced (P = 0.019) when compared with wild‐type allele carriers. Thus, in females, genetic variation causing reduced IIS activation is beneficial for old age survival. This effect was stronger for the GH1 SNP than for variation in the conserved IIS genes that were found to affect longevity in model organisms.

Plasticity in butterfly egg size : why larger offspring at lower temperatures?

Dividing sister pairs of the butterfly Bicyclus anynana (reared in a common environment) between high and low temperature shows that oviposition temperature induces a plastic response in egg size. Females at a lower temperature laid significantly larger (but fewer) eggs than their sisters kept at a higher temperature, whereas total reproductive investment increased with temperature. Cross-transfer experiments demonstrated that this plastic response in egg size is reversible. Interestingly, this pattern parallels an almost universal temperature-induced developmental response in ectotherm body size. In both cases, however, we do not yet understand the underlying mechanisms or the potential adaptive significance. By cross-transferring the experimentally manipulated eggs between temperatures, we showed that the larger eggs produced at a lower temperature had a higher hatching success, and yielded larger hatchlings with a slightly higher probability of reaching maturity and shorter larval development time (at ...

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.

Genotype x environment interaction QTL mapping in plants: lessons from Arabidopsis

Plant growth and development are influenced by the genetic composition of the plant (G), the environment (E), and the interaction between them (G×E). To produce suitable genotypes for multiple environments, G×E should be accounted for and assessed in plant-breeding programs. Here, we review the genetic basis of G×E and its consequence for quantitative trait loci (QTL) mapping in biparental and genome-wide association (GWA) mapping populations. We also consider the implications of G×E for understanding plant fitness trade-offs and evolutionary ecology.

Genes encoding longevity: from model organisms to humans

Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance and repair mechanisms that minimize age‐related accumulation of permanent damage. Here, we describe the evolutionary conserved genes that are involved in lifespan regulation of model organisms and humans, and explore the reasons of discrepancies that exist between the results found in the various species. In general, the accumulated data have revealed that when moving up the evolutionary ladder, together with an increase of genome complexity, the impact of candidate genes on lifespan becomes smaller. The presence of genetic networks makes it more likely to expect impact of variation in several interacting genes to affect lifespan in humans. Extrapolation of findings from experimental models to humans is further complicated as phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar. Finally, currently used methodologies may have only little power and validity to reveal genetic variation in the population. In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain.

The evolutionary genetics of ageing and longevity

Evolutionary theories of ageing are based on the observation that the efficacy of natural selection decreases with age. This is because, even without ageing, individuals will die of environmental causes, such as predation, disease and accidents. Ageing is thought to have evolved as the result of optimising fitness early in life. A second process, namely the progressive accumulation of mutations with effects late in life, will reinforce this result. Longevity of a species is therefore determined by the amount of environmental mortality caused by the ecology of a species. The experimental data concerning the relative roles of both processes are reviewed here. Recent discoveries of the levelling of mortality curves, and of age specific mutations in mutation accumulation lines of Drosophila melanogaster, require adjustments to the original models of the evolution of ageing and species longevity. These adjustments do not invalidate the underlying rationale of evolutionary theories of ageing. With current developments in QTL mapping and genetic association studies, the unravelling of the ageing process has the potential to progress rapidly.

How does egg size relate to body size in butterflies

Although arthropod egg size is an evolutionarily and ecologically significant trait, there is still a poor understanding of the specific factors determining it. For butterflies there is evidence from an interspecific comparison that egg size is related to adult size, suggesting a morphological constraint. Using laboratory populations of the tropical butterfly Bicyclus anynana, we show that larger eggs produce larger hatchlings, and that there is considerable intra-populational variation in egg size. However, the correlation between egg size and female size is weak and explains only 1% of the variation found within a population; even development time is a slightly better predictor for egg size than female size. We conclude that there is no evidence that body size imposes a constraint on the evolution of egg size within butterfly populations. However, populations that have diverged in body size under artificial selection show correlated responses in egg size. Thus, correlations between body size and egg size may represent an emergent property, visible only when a large range of differences in body size is considered.

Differences in the selection response of serially repeated color pattern characters: Standing variation, development, and evolution

BackgroundThere is spectacular morphological diversity in nature but lineages typically display a limited range of phenotypes. Because developmental processes generate the phenotypic variation that fuels natural selection, they are a likely source of evolutionary biases, facilitating some changes and limiting others. Although shifts in developmental regulation are associated with morphological differences between taxa, it is unclear how underlying mechanisms affect the rate and direction of evolutionary change within populations under selection.Here we focus on two ecologically relevant features of butterfly wing color patterns, eyespot size and color composition, which are similarly and strongly correlated across the serially repeated eyespots. Though these two characters show similar patterns of standing variation and covariation within a population, they differ in key features of their underlying development. We targeted pairs of eyespots with artificial selection for coordinated (concerted selection) versus independent (antagonistic selection) change in their color composition and size and compared evolutionary responses of the two color pattern characters.ResultsThe two characters respond to selection in strikingly different ways despite initially similar patterns of variation in all directions present in the starting population. Size (determined by local properties of a diffusing inductive signal) evolves flexibly in all selected directions. However, color composition (determined by a tissue-level response to the signal concentration gradient) evolves only in the direction of coordinated change. There was no independent evolutionary change in the color composition of two eyespots in response to antagonistic selection. Moreover, these differences in the directions of short-term evolutionary change in eyespot size and color composition within a single species are consistent with the observed wing pattern diversity in the genus.ConclusionBoth characters respond rapidly to selection for coordinated change, but there are striking differences in their response to selection for antagonistic, independent change across eyespots. While many additional factors may contribute to both short- and long-term evolutionary response, we argue that the compartmentalization of developmental processes can influence the diversification of serial repeats such as butterfly eyespots, even under strong selection.

Cooler butterflies lay larger eggs: developmental plasticity versus acclimation

We use a full factorial design to investigate the effects of maternal and paternal developmental temperature, as well as female oviposition temperature, on egg size in the butterfly Bicyclus anynana. Butterflies were raised at two different temperatures and mated in four possible sex–by–parental–temperature crosses. The mated females were randomly divided between high and low oviposition temperatures. On the first day after assigning the females to different temperatures, only female developmental temperature affected egg size. Females reared at the lower temperature laid larger eggs than those reared at a higher temperature. When eggs were measured again after an acclimation period of 10 days, egg size was principally determined by the prevailing temperature during oviposition, with females ovipositing at a lower temperature laying larger eggs. In contrast to widely used assumptions, the effects of developmental temperature were largely reversible. Male developmental temperature did not affect egg size in either of the measurements. Overall, developmental plasticity and acclimation in the adult stage resulted in very similar patterns of egg size plasticity. Consequently, we argue that the most important question when testing the significance of acclamatory changes is not at which stage a given plasticity is induced, but rather whether plastic responses to environmental change are adaptive or merely physiological constraints.

Evolution of Sexual Dimorphism in the Lepidoptera

Among the animals, the Lepidoptera (moths and butterflies) are second only to beetles in number of described species and are known for their striking intra- and interspecific diversity. Within species, sexual dimorphism is a source of variation in life history (e.g., sexual size dimorphism and protandry), morphology (e.g., wing shape and color pattern), and behavior (e.g., chemical and visual signaling). Sexual selection and mating systems have been considered the primary forces driving the evolution of sexual dimorphism in the Lepidoptera, and alternative hypotheses have been neglected. Here, we examine opportunities for sexual selection, natural selection, and the interplay between the two forces in the evolution of sexual differences in the moths and butterflies. Our primary goal is to identify mechanisms that either facilitate or constrain the evolution of sexual dimorphism, rather than to resolve any perceived controversy between hypotheses that may not be mutually exclusive.