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Book Summary:
Genomic sequence variation is the hallmark of life and is key to understanding diversity and adaptation among the numerous microorganisms on earth. Some genes are well conserved among all extant species to provide essential function in part required for survival. Some evolve fast to support needs of adapting to altering environment. By comparing genes from many species, this thesis establishes the existence of a special class of genes which have a modular architecture composed of both highly variable and well conserved domains. The variable domains usually do not meet any criteria to be catalogued in the conserved domain databases, and for the most part, their function remains unknown. These genes are called segmentally variable genes (SVGs), as distinguished from the well-conserved and lineage-specific ones. The variable domains in SVGS are suggested to perform important binding functions responsible for protein-protein, protein-nucleic acid, or protein-small molecule interactions. By comparing sequences of closely related genome strains, this thesis then studies genes with fast-evolving regions which reveal sequence variation and genome evolution over a relatively short evolutionary time scale. Among the ones identified are those involved in host-pathogen interactions, defense mechanisms etc., and many with unknown roles. The experimental studies in this thesis confirm the expected molecular function from one of the computational predictions on a SVG family, methionyl aminopeptidase activity, and suggest new functional clues for the variable domain. The last modular architecture in microbial genomes studied in this thesis is the conserved gene clusters. A new method is described for accurately detecting the conserved clusters in microbial genomes by utilizing information from genome phylogeny trees. The results uncover the relationship between genes and provide another adaptation mechanism of microbial genes at the genome level. |
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