Genomic methods have transformed the study of bacterial evolution, adaptation and function by enabling the rapid characterization of virtually any microorganism and microbial community. Such analyses, however, are not without shortcomings: large genomic datasets often require new tools to uncover evolutionarily meaningful patterns; signatures of selection impart little, if any, information about their ecological causes, and most current assessments of microbiomes offer only limited understanding of community contents and functions. For more than two decades, research from my laboratory has combined informatic and experimental approaches to provide new insights into the evolution of microbial genes, genomes and communities. This proposal covers three main Subject Areas, and in each, many of the questions addressed stem from observations first made by comparative genomic analysis. The first Subject Area asks how new genes and functions originate in bacterial genomes. Most models of new gene evolution are based on the duplication and modification of existing genetic information, and ignore questions about how completely new genes can arise de novo. We also ask how those genes that already exist in genomes can assume entirely new functions. The second Subject Area investigates a newly discovered selective agent that governs bacterial genomic base composition. The long-held view is that differences in genomic base composition were caused by inherent biases in the patterns of mutations (a strictly neutral process). But recent comparative sequence analyses demonstrate that mutation in bacteria is universally biased towards A+T, even in GC-rich genomes, indicating a role of selection in shaping base composition. Why and how selection operates on the base composition is not known, and no known processes can explain its mode of action, so we are investigating the source of this newly discovered selective pressure, the mechanism by which it operates, and the extent of its action. The third Subject Area addresses questions about microbial communities, newly answerable due to novel methodologies. We examine the strain-level variation among bacteria in complex communities to answer questions about how specific host-restricted microorganisms co-evolve with hosts. At the other extreme of phylogenetic depth, we will classify the currently unclassifiable organisms that often represent large fractions of microbial communities.
Our aim here is to discover new major lines of descent within the gut microbiome. Finally, we will work at the level of individual cells in complex microbial communities to elucidate how functionally relevant genes-globally importantly antibiotic resistance determinants-are distributed across divergent members of a community.

Public Health Relevance

The research examines the patterns of adaptation in bacteria that are relevant to human health. Projects investigate how pathogenic bacteria acquire new traits and functions to cope with new environments, the causes of differences in mutational rates and bacterial growth rates, the coevolution between bacteria and their hosts, and the distribution and transmission of antibiotic resistance determinants among bacteria that reside the gut microbiome. Recognition of these factors is vital to our understanding of the ways that bacteria evolve and adapt to human hosts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM118038-03
Application #
9490385
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Janes, Daniel E
Project Start
2016-06-01
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78759
Bobay, Louis-Marie; Ochman, Howard (2018) Biological species in the viral world. Proc Natl Acad Sci U S A 115:6040-6045
Traverse, Charles C; Ochman, Howard (2018) A Genome-Wide Assay Specifies Only GreA as a Transcription Fidelity Factor in Escherichia coli. G3 (Bethesda) 8:2257-2264
Raymann, Kasie; Bobay, Louis-Marie; Moran, Nancy A (2018) Antibiotics reduce genetic diversity of core species in the honeybee gut microbiome. Mol Ecol 27:2057-2066
Bobay, Louis-Marie; Ellis, Brian Shin-Hua; Ochman, Howard (2018) ConSpeciFix: classifying prokaryotic species based on gene flow. Bioinformatics 34:3738-3740
Nishida, Alex H; Ochman, Howard (2018) Rates of gut microbiome divergence in mammals. Mol Ecol 27:1884-1897
Raymann, Kasie; Moeller, Andrew H; Goodman, Andrew L et al. (2017) Unexplored Archaeal Diversity in the Great Ape Gut Microbiome. mSphere 2:
Bobay, Louis-Marie; Ochman, Howard (2017) Biological species are universal across Life's domains. Genome Biol Evol :
Traverse, Charles C; Ochman, Howard (2017) Genome-Wide Spectra of Transcription Insertions and Deletions Reveal That Slippage Depends on RNA:DNA Hybrid Complementarity. MBio 8:
Bobay, Louis-Marie; Ochman, Howard (2017) Impact of Recombination on the Base Composition of Bacteria and Archaea. Mol Biol Evol 34:2627-2636
Moeller, Andrew H; Foerster, Steffen; Wilson, Michael L et al. (2016) Social behavior shapes the chimpanzee pan-microbiome. Sci Adv 2:e1500997

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