Consequences of the accumulation of haploinsufficient genes on the mating-type chromosomes of fungi and the sex chromosomes of animals. (a) In the diploid yeast cell, loss of one copy of the mating chromosome allows expression of the mating pheromones (typically suppressed in the diploid), generating a mating-competent diploid. The accumulation of haploinsufficient (HI) genes on this chromosome is proposed to be a selective mechanism against its loss, compromising fitness in the chromosome III monosome to such a degree as to preclude diploid mating. (b) In animals, the presence of HI genes on the sex chromosomes should incur a selective penalty in the heterogametic sex. In mammals and Caenorhabditis elegans, X chromosome inactivation in the female halves the expression of the genes along the entire chromosome, resulting in selective pressure against X-linked HI genes in the homogametic sex as well. In contrast, in Drosphila melanogaster males, the expression of the lone X chromosome is doubled, thus any HI genes present on the chromosome should present no detriment to the fitness of either sex.