Chapter 15 - All cells have a sex: Sex chromosome function at the cellular level

Abstract

Shortly after the discovery of chromosomes and genes as the conveyers of heritable traits, the identification of two nonhomologous chromosomes, that were differentially expressed in males and females revealed the genetic basis of sex. Early studies suggested that all differences between males and females stemmed from the presence of sex hormones and that the only role sex chromosomes played was to generate the tissues from which those hormones could be released. However, the observation that many pathologies displayed sexually dimorphic penetrance and severity even before puberty (or indeed in utero) hinted that something in addition to sex hormones also underlay sex differences. While the female X chromosome was large enough to house several genes, it was thought that the Y chromosome only contained sufficient DNA to code for the generation of testes and their sex hormones. It is now known that there are multiple homologous genes on the X and Y chromosomes, and that many are involved in human disease and pathophysiology. In addition, genes from the sex chromosomes are expressed in all tissues of the body, including those of the immune system and the brain. This chapter explores the sex hormone independent functions of sex chromosome genes throughout the body, and highlights potential mechanistic underpinnings of how diseases differentially affect males and females. The sex chromosomes are not just expressed in gonadal tissue, but are present in every cell in the body, leading to the implication that all cells have a sex!