My major interest is in the processes and mechanisms of molecular evolution. We conduct both experimental and theoretical (statistical) studies. My current experimental projects include: 1. Molecular evolutionary genetics of color vision. Our goal is to understand the genetics, evolution, and mechanism of color vision in mammals by a combination of molecular, evolutionary, and statistical approaches. 2. Molecular clocks and rate variation among regions of a genome. We study rate differences among evolutionary lineages and we examine the regional mutation hypothesis, which postulates that the rate and pattern of mutation vary among genomic regions. From such studies we try to infer the factors (e.g., generation time, recombination rate, GC content) that may affect the rate and pattern of mutation and also the evolutionary factors responsible for rate differences among lineages. 3. Coevolution of growth hormone and its receptor. Coevolution at the molecular level remains poorly understood, though the study of coevolution may greatly increase our understanding of the process of molecular evolution. The coevolution of growth hormone and its receptor in mammals provides a fascinating system. For example, while growth hormone has been well conserved in many mammals (e.g., pig, whale, and horse), it has evolved at an extremely rapid rate in humans and Old World monkeys. On the other hand, human growth hormone receptor binds only primate growth hormone, though non-primate growth hormone receptors can bind primate growth hormone. We are therefore interested in studying how the coevolution of human growth hormone and its receptor has occurred.

The theoretical group is pursuing evolutionary genomics. We develop statistical methods and conduct statistical analyses of genomic sequence data and functional genomic data. The huge amount of genomic data generated by various genome projects is a tremendous resource for studying molecular evolution and for understanding the organization and evolution of genomes. This research requires development of tools for comparative genomics and data mining and also a systematic analysis of data. One of our current foci is the evolution of duplicate genes at the genomic level. We study how often gene duplication occurs in a genome, the factors that determine the fate of duplicate genes, how fast and how often duplicate genes diverge in expression, and how duplicate genes diverge in function.

Recent Publications

Shyue, S.-K., D. Hewett-Emmett, H. G. Sperling, D.M. Hunt, J.K. Bowmaker, J.D. Mollon and W.-H. Li (1995)

Adaptive evolution of colour vision genes in higher primates. Science 269:1265-1267

Tan, Y. and W.-H. Li (1999)

Trichromatic vision in prosimians. Nature 402:36.

Makova, K. D. and W.-H. Li (2002)

Strong male-driven evolution of DNA sequences in humans and apes. Nature 416:624-626.

Yi, S., D. L. Ellsworth, and W.-H. Li (2002)

Slow molecular clocks in Old World monkeys, apes and humans. Mol. Biol. Evol. 19:2191-2198.

Liu, J.-C., K. Makova, R.M. Adkins, S. Gibson, and W.-H. Li (2001)

Episodic evolution of growth hormone in primates and emergence of the species specificity of human growth hormone receptor. Mol. Biol. Evol. 18:945-953.

Yi, S., B. Bernat, G. Pál, A. Kossiakoff, and W.-H. Li (2002)

Functional promiscuity of squirrel monkey growth hormone receptor toward both primate and nonprimate growth hormones. Mol. Biol. Evol. 19:1083-1092.

Gu, Z., D. Nicolae, H. H.-S Lu, and W.-H. Li (2002)

Rapid divergence in expression between duplicate genes inferred from microarray gene expression data. Trend Genetics 18:609-613.

Gu, Z., L. M. Steinmetz, X. Gu, C. Scharfe, R. W. Davis, and W.-H. Li (2003)

Role of duplicate genes in genetic robustness against null mutations. Nature 421:63-66.