Evolution of an antifreeze protein by neofunctionalization under escape from adaptive conflict

Abstract

The evolutionary model escape from adaptive conflict (EAC) posits that adaptive conflict between the old and an emerging new function within a single gene could drive the fixation of gene duplication, where each duplicate can freely optimize one of the functions. Although EAC has been suggested as a common process in functional evolution, definitive cases of neofunctionalization under EAC are lacking, and the molecular mechanisms leading to functional innovation are not well-understood. We report here clear experimental evidence for EAC-driven evolution of type III antifreeze protein gene from an old sialic acid synthase (SAS) gene in an Antarctic zoarcid fish. We found that an SAS gene, having both sialic acid synthase and rudimentary ice-binding activities, became duplicated. In one duplicate, the N-terminal SAS domain was deleted and replaced with a nascent signal peptide, removing pleiotropic structural conflict between SAS and ice-binding functions and allowing rapid optimization of the C-terminal domain to become a secreted protein capable of noncolligative freezingpoint depression. This study reveals how minor functionalities in an old gene can be transformed into a distinct survival protein and provides insights into how gene duplicates facing presumed identical selection and mutation pressures at birth could take divergent evolutionary paths.Antarctic eelpouts | thermal hysteresis | tandem repeats | positive selection G ene duplication is well-recognized as an important source of new genes and functions (1), but the underlying evolutionary mechanisms are far from clear (2-5). Most conceptual models propose that mutational changes, whether neutral [mutation during nonfunctionality (MDN) or duplication degeneration complementation (DDC) model] (3, 6, 7) or directional (adaptational models) (3, 4), occur in the daughter duplicate after gene duplication, leading to subfunctionalization (partitioning of ancestral functions and specialization in one of them) and in rare instances, a new function (neofunctionalization). An alternate model, escape from adaptive conflict (EAC), recognizes that an ancestor with an emergent function besides its primary function could be subject to selection and acquire adaptive changes before gene duplication, but inadvertent pleiotropic conflicts between the two functions constrain further improvements (6,8). Gene duplication resolves the conflict, allowing daughter duplicates to separately optimize one of the functions (8-10). Resolution of adaptive conflicts created by natural selection as an intrinsic driving force of gene duplication during sub-or neofunctionalization is elegantly logical and may occur frequently, because it potentially applies whenever the ancestor gene experiencing positive selection is a generalist capable of more than one function. In fact, widespread observations of gene sharing and promiscuous function of many enzymes have raised considerable interest in the EAC model (3,11,12). However, thus far, only two studies provided evidence of gene duplication u...

Molecular basis and genetic improvement of economically important traits in aquaculture animals

“…To identify candidate cold tolerance-related and cold change-related genes, a large-scale EST sequencing of multi-tissues including brain, liver, head kidney, and ovary had been performed in Antarctic notothenioid (Dissostichus mawsoni), and some important cold-specific expressed genes had been identified by comparative transcriptome analyses between D. mawsoni and non-notothenioid warm-water teleost fishes [133,134]. Moreover, the molecular origination of antifreeze protein III (AFP III) was demonstrated to come from a duplicate copy of sialic acid synthase (SAS) gene, supporting the evolutionary mechanism by neofunctionalization under escape from adaptive conflict [135].…”

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