Evolutionary theories of ageing assume causal mutations either have beneficial early-life effects which gradually become deleterious with advancing age (antagonistic pleiotropy: AP) or mutations that only have deleterious effects at old age (mutation accumulation: MA). Mechanistically, ageing is predicted to result from damage accumulating in the soma. While this scenario is compatible with AP, it is not immediately obvious how damage would accumulate under MA. In a modified version of the MA theory, it has been suggested that mutations with weakly deleterious effects at young age can also contribute to ageing, if they generate damage that gradually accumulates with age. Mutations with increasing deleterious effects have recently gained support from theoretical work and studies of large-effect mutations. Here we address if spontaneous mutations also have negative effects that increase with age. We accumulate mutations with early-life effects in Drosophila melanogaster across 27 generations and compare their relative effects on fecundity early and late in life. Our mutation accumulation lines on average have substantially lower early-life fecundity compared to controls. These effects were further maintained throughout life, but they did not increase with age. Our results thus suggest that most spontaneous mutations do not contribute to damage accumulation and ageing.

Exposing sires to various environmental manipulations has demonstrated that paternal effects can be non-trivial also in species where male investment in offspring is almost exclusively limited to sperm. Whether paternal effects also have a genetic component (i.e. paternal indirect genetic effects - PIGEs) in such species is however largely unknown, primarily because of methodological difficulties separating indirect from direct effects of genes. PIGEs may nevertheless be important, since they have the capacity to contribute to evolutionary change. Here we use Drosophila genetics to construct a breeding design that allows testing nearly complete haploid genomes (>99%) for PIGEs. Using this technique, we estimate the variance in male lifespan due to PIGEs among four populations and compare this to the total paternal genetic variance (the sum of paternal indirect and direct genetic effects). Our results indicate that a substantial part of the total paternal genetic variance results from PIGEs. A screen of 38 haploid genomes, randomly sampled from a single population, suggests that PIGEs also influence variation in lifespan within populations. Collectively, our results demonstrate that PIGEs may constitute an underappreciated source of phenotypic variation.

Evolution of ageing requires mutations with late-life deleterious effects. Classic theories assume these mutations either have neutral (Mutation Accumulation) or beneficial (Antagonistic Pleiotropy) effects early in life, but it is also possible that they start out as mildly harmful and gradually become more deleterious with age. Despite a wealth of studies on the genetics of ageing, we still have a poor understanding of how common mutations with age-specific effects are and what ageing theory they support. To advance our knowledge on this topic we measure a set of genomic deletions for their heterozygous effects on juvenile performance, fecundity at three ages, and adult survival. Most deletions have age-specific effects, and these are commonly harmful late in life. Many of the deletions assayed here would thus contribute to ageing if present in a population. Taking only age-specific fecundity into account, some deletions support Antagonistic Pleiotropy, but the majority of them better fit a scenario where their negative effects on fecundity become progressively worse with age. Most deletions have a negative effect on juvenile performance, a fact which strengthens the conclusion that deletions primarily contribute to ageing through negative effects that amplify with age.

Lifespan differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened lifespan because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (~20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced lifespan or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in lifespan.

Dietary restriction (DR), a reduction in nutrient intake without malnutrition, is the most reproducible way to extend lifespan in a wide range of organisms across the tree of life, yet the evolutionary underpinnings of the DR effect on lifespan are still widely debated. The leading theory suggests that this effect is adaptive and results from reallocation of resources from reproduction to somatic maintenance, in order to survive periods of famine in nature. However, such response would cease to be adaptive when DR is chronic and animals are selected to allocate more resources to reproduction. Nevertheless, chronic DR can also increase the strength of selection resulting in the evolution of more robust genotypes. We evolved Drosophila melanogaster fruit flies on DR, standard and high adult diets in replicate populations with overlapping generations. After approximately 25 generations of experimental evolution, male DR flies had higher fitness than males from standard and high populations. Strikingly, this increase in reproductive success did not come at a cost to survival. Our results suggest that sustained DR selects for more robust male genotypes that are overall better in converting resources into energy, which they allocate mostly to reproduction.

Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Island's feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population-an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.

The sexes share the same autosomal genomes, yet sexual dimorphism is common due to sex-specific gene expression. When present, XX and XY karyotypes trigger alternate regulatory cascades that determine sex-specific gene expression profiles. In mammals, secretion of testosterone (T) by the testes during foetal development is the master switch influencing the gene expression pathways (male vs. female) that will be followed, but many genes have sex-specific expression prior to T secretion. Environmental factors, like endocrine disruptors and mimics, can interfere with sexual development. However, sex-specific ontogeny can be canalized by the production of epigenetic marks (epimarks) generated during early ontogeny that increase sensitivity of XY embryos to T and decrease sensitivity of XX embryos. Here, we integrate and synthesize the evidence indicating that canalizing epimarks are produced during early ontogeny. We will also describe the evidence that such epimarks sometimes carry over across generations and produce mosaicism in which some traits are discordant with the gonad. Such carryover epimarks are sexually antagonistic because they benefit the individual in which they were formed (via canalization) but harm opposite-sex offspring when they fail to erase across generations and produce gonad-trait discordances. SA-epimarks have the potential to: i) magnify phenotypic variation for many sexually selected traits, ii) generate overlap along many dimensions of the masculinity/femininity spectrum, and iii) influence medically important gonad-trait discordances like cryptorchidism, hypospadias and idiopathic hirsutism.

Hos många arter uppvisar könen en rad skillnader.Dessa omfattar vanligtvis deras utseende så väl som beteende. Vad är det egentligen som orsakar evolution av könsskillnader, hur är den möjlig då könen har i princip samma gener, och kan detta tänkas ha konsekvenser för hur vi människor fungerar?

The X chromosome constitutes a unique genomic environment because it is present in onecopy in males, but two copies in females. This simple fact has motivated several theoreticalpredictions with respect to how standing genetic variation on the X chromosome should differfrom the autosomes. Unmasked expression of deleterious mutations in males and alower census size are expected to reduce variation, while allelic variants with sexually antagonisticeffects, and potentially those with a sex-specific effect, could accumulate on theX chromosome and contribute to increased genetic variation. In addition, incomplete dosagecompensation of the X chromosome could potentially dampen the male-specific effectsof random mutations, and promote the accumulation of X-linked alleles with sexually dimorphicphenotypic effects. Here we test both the amount and the type of genetic variation onthe X chromosome within a population of Drosophila melanogaster, by comparing the proportionof X linked and autosomal trans-regulatory SNPs with a sexually concordant anddiscordant effect on gene expression. We find that the X chromosome is depleted for SNPswith a sexually concordant effect, but hosts comparatively more SNPs with a sexually discordanteffect. Interestingly, the contrasting results for SNPs with sexually concordant anddiscordant effects are driven by SNPs with a larger influence on expression in females thanexpression in males. Furthermore, the distribution of these SNPs is shifted towards regionswhere dosage compensation is predicted to be less complete. These results suggest thatintrinsic properties of dosage compensation influence either the accumulation of differenttypes of trans-factors and/or their propensity to accumulate mutations. Our findings documenta potential mechanistic basis for sex-specific genetic variation, and identify the X as areservoir for sexually dimorphic phenotypic variation. These results have general implicationsfor X chromosome evolution, as well as the genetic basis of sex-specificevolutionary change.

The effective population size (N-e) is a fundamental parameter in population genetics that influences the rate of loss of genetic diversity. Sexual selection has the potential to reduce N-e by causing the sex-specific distributions of individuals that successfully reproduce to diverge. To empirically estimate the effect of sexual selection on N-e, we obtained fitness distributions for males and females from an outbred, laboratory-adapted population of Drosophila melanogaster. We observed strong sexual selection in this population (the variance in male reproductive success was approximate to 14 times higher than that for females), but found that sexual selection had only a modest effect on N-e, which was 75% of the census size. This occurs because the substantial random offspring mortality in this population diminishes the effects of sexual selection on N-e, a result that necessarily applies to other high fecundity species. The inclusion of this random offspring mortality creates a scaling effect that reduces the variance/mean ratios for male and female reproductive success and causes them to converge. Our results demonstrate that measuring reproductive success without considering offspring mortality can underestimate N-e and overestimate the genetic consequences of sexual selection. Similarly, comparing genetic diversity among different genomic components may fail to detect strong sexual selection.