Functional Diversification of Gene Duplicates under the Constraint of Protein Structure

Gene differentiation subsequent to duplication plays a pivotal role in the evolutionary process, facilitating the generation of new functional genes. This dynamic process involves alterations in gene characteristics including protein structure, expression patterns, cellular localization, and enzymatic activity, which collectively contribute to the advent of novel functions. However, there are still relatively few reports on how multiple genes differentiate after duplication. Here we show the functional diversification of Glycoside Hydrolase Family 50 (GH50) agarases in the deep-sea bacterium Agarivorans ablus JK6, uncovering the evolutionary mechanisms behind the emergence of new enzymatic functions post-duplication. By leveraging AlphaFold for precise protein structure prediction and integrating phylogenetic analysis with experimental methods, we shed light on the structural adaptations and sequence alterations driving these enzymes’ functional differentiation. Our findings establish a distinct link between structural changes and the creation of new hydrolysis products, underscoring the significance of gene duplication in broadening the enzymatic repertoire of organisms. Furthermore, the study elucidates how these adaptations contribute to the ecological success of A.ablus JK6, highlighting the role of gene duplication in expanding the enzymatic toolkit for environmental adaptation. Through exhaustive biochemical characterization and enzymatic activity assays, we furnish insights into the agarases’ adaptive evolution, providing a thorough perspective on how genetic and structural elements contribute to the biochemical diversity and ecological prowess of marine bacteria, and also suggests new pathways for the development of bioengineered enzymes with enhanced functionalities.