Welcome to the Yi Lab

Research Interests

I am interested in understanding the genetic basis of genome evolution. Here are some of the current projects in the lab.
(Click on titles for more information and recent publications.)

Role of Mutational Origins on Genome Evolution

Mutations, especially point mutations (single nucleotide substitutions) are the main source of evolution, and instrumental in evolutionary and phylogenetic analyses. Traditionally, molecular origins of mutations were not considered in such studies. However, point mutations vary dramatically in terms of their distinctive molecular origins. For example, the most frequent types of mutations in humans and other vertebrates (over 25%) are those that are caused by methylation, while the majority of other types of point mutations occur by errors in DNA replication (for example, see (Kim et al. 2006, Yi et al. 2002, Elango et al. 2006). Since methylation and replication are two drastically different cellular mechanisms, we are investigating effects of mutational origins on evolutionary and phylogenetic studies. Here are some recent papers on this topic, on mutational origins and molecular clock (Kim et al. 2006) and evolution of nucleotide composition (Elango et al. in review).

We plan to expand this research direction to at least two more projects. First is to investigate the role of methylation-origin mutations on mammalian genome evolution in general. We have successfully implemented a computational method that can analyze methylation-origin and replication-origin mutations separately using sequence data from closely related species. Using this method, we will investigate the following specific questions: (1) do rates of methylation-origin mutations differ among different mammalian groups? The answer to this question will reveal how rapidly levels of methylation evolve. (2) Do rates of replication-dependent mutations per generation stay constant over time or do they increase as organismal complexity increases? We are also working on modeling and analyzing the effect of heterogeneous mutational inputs on molecular evolution and phylogenetics. Since mutational origins play drastically different roles on several aspects of molecular and genome evolution, it is imperative that we consider evolutionary models that explicitly account for such effect. We hope to (1) develop a computational tool for molecular evolutionary analyses, and (2) analyze the model to investigate the effect of methylation-origin mutations in mammalian genome evolution. Furthermore, we have continued interest in evaluating the effect of molecular interactions between different processes such as recombination and mutations on genome evolution (for example, Yi et al. 2004).

Kim, S.-H.*, Elango, N.*, Warden, C., Vigoda, E., and Yi, S. (2006). Heterogenous genomic molecular clocks in primates. PLoS Genetics, 2: e163. * equal contribution [Full Text]

Elango, N., J. W. Thomas, NISC Comparative Sequencing Group, and Yi, S. (2006). Variable molecular clocks in hominoids. Proc. Natl. Acad. Sci. USA. 103:1370-1375. [Abstract] [PDF, Supplementary Material]

Yi, S., Summers, T. J., Pearson, N. M., and W-H. Li. (2004). Recombination has little effect on the rate of sequence divergence in pseudoautosomal boundary 1 among humans and great apes. Genome Research, 14:37-43. [Abstract] [PDF]

Yi, S., Ellsworth, D. and W-H. Li. (2002). Slow molecular clocks in Old World monkeys, apes, and humans. Molecular Biology and Evolution. 19:2192-2198. [Abstract] [PDF]