A genome-wide test for paternal indirect genetic effects on lifespan in<i>Drosophila melanogaster</i>

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.

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Age-specific effects of deletions: implications for aging theories

Brengdahl

Kimber

Shenoi

et al. 2022

Evolution

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On aging and age-specific effects of spontaneous mutations

et al. 2023

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OBJECTIVE The effects of the Renin Angiotensin Aldosterone System in cardiovascular system has been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity and cardiovascular structure and function. METHODS We studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and plasma renin activity blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded. RESULTS The aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m 2 higher left ventricle mass index (p=0.04) and 0.11 ml/m 2 higher left atrium minimal volume index (p < 0.01). Additionally, higher log-transformed aldosterone was associated with lower left atrium maximum strain and left atrium emptying fraction (βstandardized = -0.12, p < 0.01 and - 0.15, p < 0.01, respectively). Aldosterone levels were not significantly associated with aortic measures. Log-transformed plasma renin activity was associated with lower left ventricle end diastolic volume index (βstandardized = 0.08, p=0.05). Plasma renin activity levels were not significantly associated with left atrium and aortic structural or functional differences. CONCLUSIONS Higher levels of aldosterone and plasma renin activity are associated with concentric left ventricle remodeling changes. Moreover, aldosterone was related to deleterious left atrium remodeling changes.

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A genome-wide test for paternal indirect genetic effects on lifespan inDrosophila melanogaster

et al. 2022

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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.

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A genome-wide test for paternal indirect genetic effects on lifespan inDrosophila melanogaster

Cited by 3 publications

References 77 publications

Age-specific effects of deletions: implications for aging theories

Age-specific effects of deletions: implications for aging theories

On aging and age-specific effects of spontaneous mutations

A genome-wide test for paternal indirect genetic effects on lifespan inDrosophila melanogaster

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