Genomic Balance and Sex Chromosome Dosage Compensation

Sex chromosomes originate from a homologous pair of chromosomes becoming restricted to one sex (referred to as Y in males in the X/Y system; W in females in the ZW system) via inhibition of crossing over followed by gene loss. In contrast, most other forms of chromosomal dosage change caused by meiotic or mitotic errors, or experimental aneuploidy, are strongly deleterious or lethal. The viability of individuals with the heteromorphic sex chromosomes in various species comes from the acquisition of some type of dosage compensation that counteracts any issues with “genomic imbalance”. Here we review lessons learned about gene expression modulation from experimentally produced aneuploidy and from evolutionary genomics. These lessons from genome balance principles are applied to how different examples of sex chromosome dosage compensation (Drosophila, mosquito, mammals, nematodes) have evolved to counteract any detrimental global effects on gene expression. New perspectives and questions are raised to revise ideas about sex chromosomal evolution and to direct re-analyses of previous hypotheses.