Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

doi:10.1111/evo.13434

Cited by 18 publications

(25 citation statements)

References 52 publications

(82 reference statements)

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“…A recent study further shows that the heterogametic sex tends to exhibit higher mean/maximum lifespan across a wide taxonomic range, but phylogenetic signal and sexual selection could contribute to explain this relationship [10]. In addition, recent experimental evidence shows that “unguarding” the X chromosome in females erases the sex gap in lifespan in Drosophila melanogaster [11, 12] but see [13]. A second hypothesis focuses on the role of the heteromorphic Y (or W) chromosome.…”

Section: Mainmentioning

confidence: 99%

“…Moreover, this phenomenon influences chromatin integrity and gene expression profiles genome-wide [16], and is more acute in old males than in old females [17, 18]. Therefore, in D. melanogaster there is solid evidence of substantial “toxic Y” effects, via both the accumulation of deleterious mutations and repetitive DNA elements, resulting in increased mortality of the heterogametic sex [13, 14]. However, the role of the “toxic Y” hypothesis in explaining broad patterns of sex differences in ageing has yet to be addressed.…”

Section: Mainmentioning

confidence: 99%

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Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect

Sultanova

Downing

Carazo

2020

Preprint

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26Sex-specific lifespans are ubiquitous across the tree of life and exhibit broad taxonomic 27 patterns that remain a puzzle, such as males living longer than females in birds and vice versa 28 in mammals. The prevailing "unguarded-X" hypothesis (UXh) explains this by differential 29 expression of recessive mutations in the X/Z chromosome of the heterogametic sex (e.g., 30females in birds and males in mammals), but has only received indirect support to date. An 31 alternative hypothesis is that the accumulation of deleterious mutations and repetitive 32 elements on the Y/W chromosome might lower the survival of the heterogametic sex ("toxic 33 Y" hypothesis). Here, we report lower survival of the heterogametic relative to the 34 homogametic sex across 138 species of birds, mammals, reptiles and amphibians, as expected 35 if sex chromosomes shape sex-specific lifespans. We then analysed bird and mammal 36 karyotypes and found that the relative sizes of the X and Z chromosomes are not associated 37 with sex-specific lifespans, contrary to UXh predictions. In contrast, we found that Y size 38 correlates negatively with male survival in mammals, where toxic Y effects are expected to be 39 particularly strong. This suggests that small Y chromosomes benefit male lifespans. Our 40 results confirm the role of sex chromosomes in explaining sex differences in lifespan, but 41indicate that, at least in mammals, this is better explained by "toxic Y" rather than UXh 42 effects. 43 44 45 46 47 48 MAIN 52Sexual dimorphism in lifespan is widespread across the tree of life, including among tetrapods 53[1]. Which sex lives longer varies considerably in both direction and magnitude. For example, 54 females live three times longer than males in the brown antechinus, a small marsupial, while 55 males are twice as likely as females to survive from one year to the next in Arabian babblers, 56 a passerine bird [2, 3]. In humans, the lifespan gap is estimated to be 4.8 years -female life 57 expectancy is 74.7 years while male life expectancy is 69.9 years [4]. Understanding the 58 dynamic nature of sex differences in lifespan across taxa remains an unsolved problem in 59 evolutionary biology. To date, empirical studies have focused on adaptive hypotheses 60 stemming from sex-specific differences in how natural selection operates on females and 61 males [1, 5-8]. Despite their prominent role in explaining sex differences in ageing, adaptive 62processes seem unable to explain the observation that the homogametic sex tends to live 63 longer than the heterogametic sex across a wide taxonomic range [1, 9]. 64 65There are at least two reasons why sex chromosomes should directly contribute to the 66 evolution of different female and male lifespans [9, 10]. First, the unguarded X hypothesis 67 (UXh) predicts increased mortality of the heterogametic sex due to the expression of 68 deleterious recessive mutations that accumulate in the non-recombining parts of the X (or Z) 69 chromosome [10]. Because these mutations are masked in the homogametic s...

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Section: Mainmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect

Sultanova

Downing

Carazo

2020

Preprint

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“…However, it is difficult to imagine how these effects could mediate female-specific responses in reproductive aging when condition is altered, especially here where we controlled for maternal effects. No support for the unguarded-X hypothesis was found in the most direct test of this hypothesis yet (Brengdahl et al 2018a), but more indirect tests have found patterns consistent with this possibility (Pipoly et al 2015;Carazo et al 2016;Sultanova et al 2018). In any case, it also seems difficult to construct a scenario where X-linked recessive mutations could cause a response in female but not male reproductive aging when condition is altered.…”

Section: Genetic Quality and Sex-specific Aging 767mentioning

confidence: 99%

“…Here we briefly describe the creation of our A2 inbred lines; see figure S1B in Brengdahl et al (2018a) for more detail. We began by randomly sampling 44 males from a recently made replica of the Dahomey population that had a marked A2 balancer (CyO, Duox Cy , cn 2 , dpy lvl , pr 1 ) backcrossed into it and maintained in a heterozygous state.…”

Section: Creation Of Chromosome Homozygote Linesmentioning

confidence: 99%

Genetic Quality Affects the Rate of Male and Female Reproductive Aging Differently in Drosophila melanogaster

Brengdahl¹,

Kimber²,

Maguire-Baxter³

et al. 2018

The American Naturalist

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Dryad data: https://dx.doi.org/10.5061/dryad.5089j74.abstract: Males and females often maximize fitness by pursuing different reproductive strategies, with males commonly assumed to benefit more from increased resource allocation into current reproduction. Such investment should trade off with somatic maintenance and may explain why males frequently live shorter than females. It also predicts that males should experience faster reproductive aging. Here we investigate whether reproductive aging and life span respond to condition differently in male and female Drosophila melanogaster, as predicted if sexual selection has shaped male and female resourceallocation patterns. We manipulate condition through genetic quality by comparing individuals inbred or outbred for a major autosome. While genetic quality had a similar effect on condition in both sexes, condition had a much larger general effect on male reproductive output than on female reproductive output, as expected when sexual selection on vigor acts more strongly on males. We find no differences in reproductive aging between the sexes in low condition, but in high condition reproductive aging is relatively faster in males. No corresponding sex-specific change was found for life span. The sex difference in reproductive aging appearing in high condition was specifically due to a decreased aging rate in females rather than any change in males. Our results suggest that females age slower than males in high condition primarily because sexual selection has favored sex differences in resource allocation under high condition, with females allocating relatively more toward somatic maintenance than males.

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“…According to the refugium hypothesis proposed here, we predict that in species with a high toxicity index (i.e., excess of intact TEs on the SLCs and/or paucity thereof in the rest of the genome) this toxic effect to be more accentuated (Figure 2A and B). The toxic-Y hypothesis has been recently investigated from a theoretical point of view in vertebrates with both XY and ZW systems [47] and put in contrast to the classic "unguarded-X" hypothesis [48][49][50], which proposes that the expression of recessive mutations on X/Z chromosomes is the cause of the shorter lifespan in the heterogametic sex. Sultanova et al [47] used the sizes of Y and W relative to X and Z as a proxy for toxicity, i.e., assuming that smaller SLCs are more repetitive.…”

Section: Sex-biased Implications For Mutational Loadmentioning

confidence: 99%

The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities

Peona

Palacios-Gimenez

Blommaert

et al. 2020

Preprint

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It is a broadly observed pattern that the non-recombining regions of sex-limited chromosomes (Y and W) accumulate more repeats than the rest of the genome, even in species like birds with a low genome-wide repeat content. Here we show that in birds with highly heteromorphic sex chromosomes, the W chromosome has a transposable element (TE) density of >55% compared to the genome-wide density of <10%, and contains over half of all full-length (thus potentially active) endogenous retroviruses (ERVs) of the entire genome. Using RNA-seq and protein mass spectrometry data, we were able to detect signatures of female-specific ERV expression. We hypothesise that the avian W chromosome acts as a refugium for active ERVs, likely leading to female-biased mutational load that may influence female physiology similar to the "toxic-Y" effect in Drosophila. Furthermore, Haldane's rule predicts that the heterogametic sex has reduced fertility in hybrids. We propose that the excess of W-linked active ERVs over the rest of the genome may be an additional explanatory variable for Haldane's rule, with consequences for genetic incompatibilities between species through TE/repressor mismatches in hybrids. Together, our results suggest that the sequence content of female-specific W chromosomes can have effects far beyond sex determination and gene dosage.

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Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis

Cited by 18 publications

References 52 publications

Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect

Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect

Genetic Quality Affects the Rate of Male and Female Reproductive Aging Differently in Drosophila melanogaster

The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities

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