Abstract
In this first lecture, I present the various mechanisms, both genetic and epigenetic, that have been exploited throughout evolution to determine sex in different organisms. In mammals, where an XX (female)/XY (male) system exists, the transcription factor Sry determines male sex, while the absence of Sry and the nuclear hormone receptor DAX1 contribute to female sex.
Nevertheless, the rules seem complex, as recent research indicates that a delicate balance exists between male and female signaling pathways for sex determination. Moreover, this balance seems to be different during embryogenesis and in adulthood.
Next, I analyze how differences in gene content between males and females can pose a dosing problem. The Y chromosome often carries far fewer genes than the X chromosome - the presence of two X chromosomes in females versus one in males can have detrimental effects. We know that chromosomal monosomies or trisomies are almost always fatal to normal organisms.
On the other hand, changes in the number of copies of a single gene can cause problems (haploid insufficiency). Therefore, maintaining correct gene dosage at multiple scales (from single genes to whole chromosomes) is important. Various dose compensation strategies have evolved in different species. Inactivation of one of the two X chromosomes in XX individuals (with or without Y) is the strategy exploited in mammals.
