| 1. |
- Iinatti Brengdahl, Martin, 1990-, et al.
(författare)
-
Age-specific effects of deletions: Implications for ageing theories
- 2022
-
Annan publikationabstract
- 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.
|
|
| 2. |
- Iinatti Brengdahl, Martin, et al.
(författare)
-
Age-specific effects of deletions: implications for aging theories
- 2023
-
Ingår i: Evolution. - : OXFORD UNIV PRESS. - 0014-3820 .- 1558-5646. ; 77:1, s. 254-263
-
Tidskriftsartikel (refereegranskat)abstract
- The evolution of aging 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 aging, we still have a poor understanding of how common mutations with age-specific effects are and what aging 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 3 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 aging 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 that strengthens the conclusion that deletions primarily contribute to aging through negative effects that amplify with age.
|
|
| 3. |
- Malacrino, Antonino, et al.
(författare)
-
Ageing desexualizes the Drosophila brain transcriptome
- 2022
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - London : The Royal Society Publishing. - 0962-8452 .- 1471-2954. ; 289:1980
-
Tidskriftsartikel (refereegranskat)abstract
- General evolutionary theory predicts that individuals in low condition should invest less in sexual traits compared to individuals in high condition. Whether this positive association between condition and investment also holds between young (high condition) and senesced (low condition) individuals is however less clear, since elevated investment into reproduction may be beneficial when individuals approach the end of their life. To address how investment into sexual traits changes with age, we study genes with sex-biased expression in the brain, the tissue from which sexual behaviours are directed. Across two distinct populations of Drosophila melanogaster, we find that old brains display fewer sex-biased genes, and that expression of both male-biased and female-biased genes converges towards a sexually intermediate phenotype owing to changes in both sexes with age. We further find that sex-biased genes in general show heightened age-dependent expression in comparison to unbiased genes and that age-related changes in the sexual brain transcriptome are commonly larger in males than females. Our results hence show that ageing causes a desexualization of the fruit fly brain transcriptome and that this change mirrors the general prediction that low condition individuals should invest less in sexual phenotypes.
|
|
| 4. |
- Naresh, Vinesh Shenoi, et al.
(författare)
-
A genome-wide test for paternal indirect genetic effects on lifespan in Drosophila melanogaster
- 2022
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 289:1974
-
Tidskriftsartikel (refereegranskat)abstract
- 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 (more than 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.
|
|
| 5. |
- Naresh, Vinesh Shenoi, et al.
(författare)
-
On aging and age-specific effects of spontaneous mutations
- 2023
-
Ingår i: Evolution. - : Oxford University Press. - 0014-3820 .- 1558-5646. ; 77:8, s. 1780-1790
-
Tidskriftsartikel (refereegranskat)abstract
- Evolutionary theory assumes that mutations that cause aging either have beneficial early-life effects that gradually become deleterious with advancing age (antagonistic pleiotropy [AP]) or that they only have deleterious effects at old age (mutation accumulation [MA]). Mechanistically, aging 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 aging, 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 suggest that most spontaneous mutations do not contribute to damage accumulation and aging.
|
|
| 6. |
- Shenoi Naresh, Vinesh, et al.
(författare)
-
A genome-wide test for paternal indirect genetic effects on lifespan in Drosophila melanogaster
- 2022
-
Annan publikationabstract
- 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.
|
|
