Abstract
Abnormalities in chromosome dose can reduce organismal fitness and viability by disrupting the balance of gene expression. Unlike imbalances in chromosome dose that cause pathologies, differences in X-chromosome dose that determine sex are well tolerated. Dosage compensation mechanisms have evolved in diverse species to balance X-chromosome gene expression between sexes. Mechanisms underlying nematode X-chromosome counting to determine sex revealed how small quantitative differences in molecular signals are translated into dramatically different developmental fates. Mechanisms underlying X-chromosome dosage compensation revealed the interplay between chromatin modification and three-dimensional chromosome structure imposed by an X-specific condensin complex to regulate gene expression over vast chromosomal territories. In a surprising twist of evolution, this dosage-compensation condensin complex also regulates lifespan and tolerance to proteotoxic stress.