Our long-term objectives are to understand the mechanisms of DNA evolution and to elucidate the evolutionary history of genes and organisms.
The specific aims for the next five years are to study: 1. Methods for estimating the number of nucleotide substitutions under nonequilibrium conditions. 2. Methods of tree reconstruction. a. Statistical tests. New tests will be developed. Within population variation effects will be incorporated. The rigorousness and efficiency of the bootstrap approach will be examined. b. Tree reconstruction under unequal rates of evolution. A method suitable for inferring deep branchings in the living world, e.g., the origin of eukaryotes, will be developed. The reliability of outgroups will be studied. 3. Deletions and insertions in sequence evolution: their frequency and location of occurrence, the size of gap events and the relative frequencies of spontaneous deletion and insertion. These questions will be studied in pseudogenes, introns, spacer regions and coding regions. The hypothesis that spontaneous deletion occurs more often than spontaneous insertion will be tested. 4. Population genetics of short tandem repeats and the rate and pattern of mutation to new length alleles. 5. Evolution of cellular fatty acid- and retinol-binding proteins and related proteins. A phylogenetic tree will be constructed for members of this superfamily, and used to infer how different structural domains have been modified in evolution. One interesting question is whether heart fatty acid-binding protein (FABP) is more distantly related to liver and intestine FABPs than to other members of the superfamily. The rate of evolution will be calculated and used to infer the stringency of structural requirements in each domain of the proteins. The hypothesis that serum retinol binding protein is related to members of this superfamily will be tested. 6. The origin, age, and phylogeny of eukaryotes. The origin of the eukaryotic nucleus and the date of the eukaryote-prokaryote divergence will be inferred. The phylogeny of eukaryotic microorganisms will be reconstructed with particular interests in the earliest branching in eukaryotes, the date of this branching, and the evolutionary position of the ciliates and the dinoflagellates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030998-16
Application #
2900564
Study Section
Genetics Study Section (GEN)
Project Start
1982-07-01
Project End
2000-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Ha, Misook; Hong, Soondo; Li, Wen-Hsiung (2013) Predicting the probability of H3K4me3 occupation at a base pair from the genome sequence context. Bioinformatics 29:1199-205
Tseng, Yan Yuan; Li, Wen-Hsiung (2012) Classification of protein functional surfaces using structural characteristics. Proc Natl Acad Sci U S A 109:1170-5
Rest, Joshua S; Bullaughey, Kevin; Morris, Geoffrey P et al. (2012) Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast. PLoS One 7:e32274
Woo, Yong H; Li, Wen-Hsiung (2012) Evolutionary conservation of histone modifications in mammals. Mol Biol Evol 29:1757-67
Lin, Zhenguo; Li, Wen-Hsiung (2012) Evolution of 5' untranslated region length and gene expression reprogramming in yeasts. Mol Biol Evol 29:81-9
Yun, Jieun; Frankenberger, Casey A; Kuo, Wen-Liang et al. (2011) Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. EMBO J 30:4500-14
Lin, Zhenguo; Li, Wen-Hsiung (2011) The evolution of aerobic fermentation in Schizosaccharomyces pombe was associated with regulatory reprogramming but not nucleosome reorganization. Mol Biol Evol 28:1407-13
Lin, Zhenguo; Li, Wen-Hsiung (2011) Expansion of hexose transporter genes was associated with the evolution of aerobic fermentation in yeasts. Mol Biol Evol 28:131-42
Chen, Sean Chun-Chang; Chuang, Trees-Juen; Li, Wen-Hsiung (2011) The relationships among microRNA regulation, intrinsically disordered regions, and other indicators of protein evolutionary rate. Mol Biol Evol 28:2513-20
Tseng, Yan Yuan; Li, Wen-Hsiung (2011) Evolutionary approach to predicting the binding site residues of a protein from its primary sequence. Proc Natl Acad Sci U S A 108:5313-8

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