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Evolution of substrate specificity in a retained enzyme driven by gene loss
Ana Lilia Juárez-Vázquez1, Janaka N Edirisinghe2,3, Ernesto A Verduzco-Castro1
1Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
Elife
|April 1, 2017
Summary
Bacterial gene loss in human cavities leads to enzyme adaptation. The phosphoribosyl isomerase A (priA) gene evolves reduced function as L-histidine and L-tryptophan pathways are lost.
Area of Science:
- Microbial genomics
- Evolutionary biology
- Biochemistry
Background:
- Gene loss is a significant evolutionary mechanism, but its impact on protein function is not well understood.
- Bacterial genomes, particularly those in host-associated environments, undergo dynamic changes including gene reduction.
- Understanding how retained proteins adapt functionally is crucial for comprehending genome evolution.
Purpose of the Study:
- To investigate the link between gene loss and functional adaptation of proteins in bacteria.
- To identify bacterial species undergoing genome reduction and analyze the consequences for metabolic pathways.
- To characterize the evolutionary trajectory of the phosphoribosyl isomerase A (priA) gene in relation to gene loss.
Main Methods:
- Phylogenomic analysis to detect bacterial species with significant gene loss.
- Metabolic modeling to assess the impact of gene loss on metabolic pathways.
- Sequence and X-ray structural analyses of phosphoribosyl isomerase A (PriA) homologs.
- Comparative analysis of PriA enzyme function across different genome sizes.
Main Results:
- Actinomycetaceae genomes from human oral cavities exhibit substantial gene loss, including pathways for L-histidine and L-tryptophan biosynthesis.
- The dual-substrate phosphoribosyl isomerase A (priA) gene shows coevolution with the presence/absence of the L-histidine (his) and L-tryptophan (trp) biosynthesis genes.
- PriA enzymes transition from a bifunctional state in larger genomes to a monofunctional, less efficient state in reduced genomes.
- Mutations arising from relaxed purifying selection drive these functional changes in PriA.
Conclusions:
- Gene loss can be a major driver of functional adaptation in retained enzymes, leading to altered substrate specificity.
- The evolution of PriA's substrate specificity is linked to genome reduction and the loss of associated metabolic pathways.
- This study provides insights into how enzymes adapt to changing metabolic environments driven by gene loss.