No abstract

Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. To date, studies of LOY have only been performed in humans, and so it is unclear whether LOY is a natural consequence of our relatively long lifespan or due to exposure to human-specific external stressors. Here, we explored whether LOY could be detected in rats. We applied a locus-specific PCR and target sequencing approach that we used as a proxy to estimate LOY in 339 samples covering eleven tissues from young and old individuals. We detected LOY in four tissues of older rats. To confirm the results from the PCR screening, we re-sequenced 60 full genomes from old rats, which revealed that the Y chromosome is the sole chromosome with low copy numbers. Finally, our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome. This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and conclude that LOY may be a natural process in placental mammals.

Females and males often exhibit different survival in nature, and it has been hypothesized that sex chromosomes may play a role in driving differential survival rates. For instance, the Y chromosome in mammals and the W chromosome in birds are often degenerated, with reduced numbers of genes, and loss of the Y chromosome in old men is associated with shorter life expectancy. However, mosaic loss of sex chromosomes has not been investigated in any non-human species. Here, we tested whether mosaic loss of the W chromosome (LOW) occurs with ageing in wild birds as a natural consequence of cellular senescence. Using loci-specific PCR and a target sequencing approach we estimated LOW in both young and adult individuals of two long-lived bird species and showed that the copy number of W chromosomes remains constant across age groups. Our results suggest that LOW is not a consequence of cellular ageing in birds. We concluded that the inheritance of the W chromosome in birds, unlike the Y chromosome in mammals, is more stable.