Mammalian genome evolution through the lens of the sex chromosomes
Open Access
- Author:
- Wilson Sayres, Melissa Ann
- Graduate Program:
- Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 18, 2011
- Committee Members:
- Kateryna Dmytrivna Makova, Dissertation Advisor/Co-Advisor
Kateryna Dmytrivna Makova, Committee Chair/Co-Chair
Webb Colby Miller, Committee Member
Stephen Wade Schaeffer, Committee Member
Eddie Holmes, Committee Member
Laura Carrel, Committee Member - Keywords:
- evolution
genomes
evolution
sex chromosomes
mammals - Abstract:
- I begin this dissertation by conducting a comprehensive review of mammalian sex chromosome evolution, then proceed to describe my novel contributions to the field, and conclude by summarizing the significance and possible future directions of my research. Chromosomal sex determination is such an efficient mechanism of determining sex that it has arisen, independently, in multiple lineages, spanning species as diverse as plants, animals and fungi. Sex chromosomes can be either male or female heterogametic, and the heterogametic sex can be different between closely related species. Mammals have a male-heterogametic sex chromosome system where both males and females have two copies of each autosome (non-sex chromosome), males have a single X chromosome and a single, degenerating, Y chromosome, and females have two X chromosomes. Since the sex chromosomes diverged from an ancestral autosomal pair, the X has remained relatively gene-rich, while the Y has lost most of its genes through the accumulation of deleterious mutations in its nonrecombining regions. Curiously, I found that genes on the X and Y acquired distinct evolutionary rates immediately following the suppression of recombination between the two sex chromosomes. The Y-linked genes evolved at higher rates, while the X-linked genes maintained the lower evolutionary rates of the ancestral autosomal genes. These distinct rates have been maintained throughout the evolution of X and Y. Specifically, I found that in human, most X gametologs and, curiously, also most Y gametologs evolved under stronger purifying selection than similarly aged autosomal paralogs. The unique mRNA/protein expression patterns and functions acquired by Y (versus X) gametologs likely contributed to their retention. My analyses of X-linked genes that do, or likely did, have homologous Y-linked sequence suggests that most features of X-linked genes investigated do not have the power to determine which Y-linked genes will be lost or retained over time. Specifically, I concluded that there are no significant differences in the expression, association with disease, or selective constraints of X-linked genes, whether they do or do not have functional Y-homologs. In contrast, I discovered that the X-inactivation status of an X-linked gene is remarkably successful in predicting whether an X-linked gene has Y-linked sequence (68% success rate) or whether its homologous Y sequence has been completely lost (92% success rate). Lastly, because they spend different amounts of time in the male and female germlines, I compared differences in the substitution rates on the X chromosome and autosomes to approximate the ratio of the male mutation rate to the female mutation rate, α. In mammals, although α varies, I confirmed that it is generally greater than 1, indicating a male mutation bias (i.e., that there are more mutations incorporated into the male germline than the female germline). By correlated variations in life history traits with α, and, separately, with genome substitution rates, I showed that variations in predictors of generation time are the strongest predictors of variations in both α and sex-averaged substitution rates at unconstrained sites. I found that variation in predictors of metabolic rate are secondarily important to predicting variation in both α and substitution rates, losing their significance when included in multiple regression models that include predictors of generation time. Finally, contrary to many expectations, I showed that variations in sperm competition, which occurs when sperm from multiple males must compete to fertilize the eggs of a single female, does not have significant predictive power of the variation in α or substitution rates across mammals.