A fundamental understanding of microbial genome and species evolution, as well as human genome evolution, is important for public health and medical science. This proposal addresses the concept of codivergence, i.e., the divergence of one gene or species lineage concomitantly with the divergence of another. In this process two or more lineages stay closely associated with one another: In this process two or more lineages stay closely associated with one another: genes with species and hosts with pathogens, parasites or symbionts. Deviations from codivergence that are increasingly recognized in pathogen and human genomes include gene duplications, lateral gene transfers between species, retention of ancestral polymorphisms by balancing selection, and accelerated evolution by neofunctionalization. This project will bring together complementary expertise and cross-train students in algebraic geometry and mathematical biology, molecular biology and evolution of symbiotic systems, and computer science and bioinformatics. The investigators propose to: (1) develop a new statistical model and corresponding methods and algorithms for simultaneous derivation of pairs of gene trees to allow rigorous tests of their codivergence or deviation from codivergence;(2) design and develop software that efficiently implements these new methods;and (3) apply such methods to the large number of genes available from genome sequences in order to better assess the history of speciation and genome evolution. Unlike existing methods based on independently constructed phylogenetic trees, a novel statistical model is proposed based on polyhedral and algebraic geometry to determine whether sets of gene sequences exhibit codivergence. The method will develop two or more trees jointly, to better reflect the properties of codivergent lineages. This approach will be implemented together with phylogenomic tools to characterize ancestral genomes or species, modeling most-recent common ancestor species as """"""""clouds"""""""" of associated gene lineages with related but nonidentical gene tree topologies. Because exact algorithms for these techniques will be computationally impractical for genome-scale data sets, heuristics and approximations will also be developed and tested. The proposed methods will be applicable to a broad array of biological problems, such as identifying codivergent and noncodivergent gene sets in whole genomes, evaluating possible host-parasite codivergence and coevolution, and testing codivergence of modules in multi-modular enzymes. In this project, teams of students, both graduate and undergraduate from all of the represented disciplines, will conduct joint projects. They will learn how to gather sequence data, design and use bioinformatic tools, and analyze biological data with mathematics and statistics to infer gene and species relationships. Additionally, a new phylogenetics course, building on an existing interdisciplinary Informatics Certificate curriculum, will be offered to graduate students.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM086888-04
Application #
8104049
Study Section
Special Emphasis Panel (ZGM1-CBCB-5 (BM))
Program Officer
Eckstrand, Irene A
Project Start
2008-08-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$274,428
Indirect Cost
Name
University of Kentucky
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Saikkonen, Kari; Young, Carolyn A; Helander, Marjo et al. (2016) Endophytic Epichloë species and their grass hosts: from evolution to applications. Plant Mol Biol 90:665-75
Young, Carolyn A; Schardl, Christopher L; Panaccione, Daniel G et al. (2015) Genetics, genomics and evolution of ergot alkaloid diversity. Toxins (Basel) 7:1273-302
Berry, Daniel; Takach, Johanna E; Schardl, Christopher L et al. (2015) Disparate independent genetic events disrupt the secondary metabolism gene perA in certain symbiotic Epichloë species. Appl Environ Microbiol 81:2797-807
Weyenberg, Grady; Huggins, Peter M; Schardl, Christopher L et al. (2014) kdetrees: Non-parametric estimation of phylogenetic tree distributions. Bioinformatics 30:2280-7
Pan, Juan; Bhardwaj, Minakshi; Nagabhyru, Padmaja et al. (2014) Enzymes from fungal and plant origin required for chemical diversification of insecticidal loline alkaloids in grass-Epichloë symbiota. PLoS One 9:e115590
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Pan, Juan; Bhardwaj, Minakshi; Faulkner, Jerome R et al. (2014) Ether bridge formation in loline alkaloid biosynthesis. Phytochemistry 98:60-8
Schardl, Christopher L; Florea, Simona; Pan, Juan et al. (2013) The epichloae: alkaloid diversity and roles in symbiosis with grasses. Curr Opin Plant Biol 16:480-8
Schardl, Christopher L; Young, Carolyn A; Pan, Juan et al. (2013) Currencies of mutualisms: sources of alkaloid genes in vertically transmitted epichloae. Toxins (Basel) 5:1064-88
Schardl, Christopher L; Young, Carolyn A; Hesse, Uljana et al. (2013) Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci. PLoS Genet 9:e1003323

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