國立清華大學 數學系

Abstract: Driven by random genetic drift, subfunctionalization enables the retention of duplicate genes in species with small population, where widespread deleterious mutations may cause complementary loss of subfunctions across gene copies. Thus, duplicates become indispensable to maintain the functional requirements of the ancestral locus. We show that subfunctionalization must be also adaptive since it buffers evolutionarily related dosage imbalances in the concentrations of encoded proteins. Dosage imbalance effects become paramount when proteins rely obligatorily on stabilizing associations to maintain structural integrity. To establish the impact of dosage-related selection pressure on gene duplication, we determined the packing quality of encoded proteins, a structural determinant of dosage sensitivity, and correlate this parameter with the extent of paralog segregation in humans, using species with larger population as controls. Recognizing subfunctionalization as an imbalance buffer enabled us to reconcile its nonadaptive origin with the adaptive impact on the evolution of genetic redundancy.