A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications

The dominance of wild-type alleles and the concomitant recessivity of deleterious mutant alleles might have evolved by natural selection or could be a by-product of the molecular and physiological mechanisms of gene action. We compared the properties of human haplosufficient genes, whose wild-type alleles are dominant over loss-of-function alleles, with haploinsufficient (recessive wild-type) genes, which produce an abnormal phenotype when heterozygous for a loss-of-function allele. The fraction of haplosufficient genes is the highest among the genes that encode enzymes, which is best compatible with the physiological theory. Haploinsufficient genes, on average, have more paralogs than haplosufficient genes, supporting the idea that gene dosage could be important for the initial fixation of duplications. Thus, haplo(in)sufficiency of a gene and its propensity for duplication might have a common evolutionary basis.