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

Abstract

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...

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

“…Sultanova et al . [ 48 ] 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.…”

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

“…It is important to note that reduced female lifespan in birds has been document in many species [52–55]. Sultanova et al [48] 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. Although the correlation between the Y size and relative lifespan in mammals was strong, the authors did not find such a correlation for the W in birds.…”

“…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.…”

“…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. Although the correlation between the Y size and relative lifespan in mammals was strong, the authors did not find such a correlation for the W in birds.…”

Epigenetics drive the evolution of sex chromosomes in animals and plants

“…Y toxicity might differ among sex chromosome systems depending on how TE-rich the Y chromosome is. An analysis conducted on several animal species suggests that male longevity is more severely affected when the Y chromosome represents a larger part of the genome [99]. This could offer an explanation for why the Y chromosome is often much smaller than its X counterpart in old sex chromosome systems, an observation that is not well understood.…”