Dynamics of mammalian X and Y chromosomes in evolution and development

Abstract

The evolution of the heterologous sex chromosomes in mammals is a fascinating phenomenon that has been the topic of many investigations and heated debates. X and Y evoived from a pair of homoiogous autosomes, and the Y chromosome has lost most of its genes along the way, while the X stayed intact, and even gained importance. This evolutionary process has led to gene dosage inequality of X chromosomal genes between males and females. In addition, in males, a dosage inequality was also created between autosomal genes that are expressed from two copies and X linked genes that are expressed from one copy. To restore the balance, dosage compensation mechanisms have co-evolved with the progressing divergence between X and Y. Placental mammals equalize these dosage inequalities by upregulating gene expression from one of the X chromosomes in both sexes, and inactivation of one X in diploid female cells by the X chromosome inactivation (XCI) machinery. XCI occurs at a very early stage of mammalian development, in the early embryo, and is regulated by many factors. Furthermore, during spermatogenesis, the X and Y chromosomes are inactivated by a process called meiotic sex chromosome inactivation (MSCI). The overall aim of the work presented and discussed in this thesis is to gain more insight into the evolutionary origin, dynamics, and fate of the mammalian sex chromosomes in relation to their functions in sex determination, gametogenesis, and development.