The preservation of duplicate genes by complementary, degenerative mutations and the origin of organismal complexity

The origin of organismal complexity is thought to be tightly coupled to the evolution of new gene functions arising subsequent to gene duplication. The classical model of gene duplication suggests that one member of a redundant, duplicate gene pair may ultimately either (1) become a pseudogene, or (2) acquire a new adaptive function and become permanently preserved. Because degenerative null mutations are far more frequent than beneficial mutations, most redundant copies will become pseudogenes. Empirical data obtained for polyploid-derived genomes suggests that far more gene duplicates are preserved than the classical model predicts.;This dissertation presents a new conceptual framework, the duplication-degeneration-complementation (DDC) model that recognizes the regulatory complexity of eukaryotic genes, and suggests a third fate for duplicate genes: subfunctionalization. The subfunctionalization hypothesis proposes that both members of a duplicate gene pair may experience complementary degenerative mutations that reduce their joint levels and expression patterns to that of the ancestral gene. The DDC model predicts that the usual mechanism of duplicate-gene preservation is the partitioning of ancestral functions, rather than the evolution of novel functions. Our analytical results and computer simulations show that under reasonable parameters, the probability of subfunctionalization is a viable mechanism for duplicate gene preservation in populations smaller than 105. Furthermore, partial loss-of-function mutations or more subfunctions elevate the probability of preservation. Because duplicate gene preservation may occur in the absence of the evolution of new gene functions, increases in morphological complexity may not accompany increases in gene number.;A current hypothesis suggests large-scale gene duplications facilitated the evolution of morphological innovations that distinguished early vertebrates from ancestral chordates. This hypothesis predicts extant agnathans should bear a record of these events in their genomes. Therefore, we have cloned and analyzed hox genes from lamprey, an agnathan. Our analysis suggests that one hox cluster duplication could have occurred before the evolution of vertebrate developmental innovations.;This dissertation redefines our understanding of the role of gene duplication in the origin of novel gene functions and the mechanisms available for duplicate gene preservation. Previously published and co-authored material is included in this dissertation.