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My major interest is in the processes and mechanisms of molecular and genomic evolution, using both experimental and theoretical approaches. Current projects include:

I. Evolution of gene regulation.

The importance of regulatory evolution has been proposed long ago (for instance, in the conspicuous morphological differences between human and chimp), but it has not been well studied due to experimental limitations. Making use of recent advances we are pursuing the following studies:

(1) Evolution of gene regulation in yeast strains and species. Our major question is whether evolution of gene regulation is mainly due to changes in cis elements or in trans factors. We are using microarrays and real time PCR to study expression differences, computational analysis of genomic data to identify sites of interest, and site-directed mutagenesis and fitness assays to test effects of regulatory changes.

(2) Evolution of gene expression patterns in mammals. Using data in the public domain, and in collaboration with other labs, we are investigating changes in tissue expression patterns between species or duplicate genes.

(3) Evolution of cis-regulatory modules and gene networks. Using statistical and experimental approaches we are identifying cis elements and gene networks, and studying how they have evolved.

II. Evolution of duplicate genes.

Gene duplication is a major source of raw material during genome evolution, and the analysis of duplicate genes provides insight into many evolutionary processes. We study patterns of duplicate gene survival across diverse genomes and what factors, such as gene structure, expression, or protein interaction, influence these patterns. We also study rates and mechanisms of structural and functional divergence in duplicate genes.

III. Development of statistical methods and computational analysis of genomic data.

The huge amount of genomic data currently available is a tremendous resource for understanding the organization and evolution of genomes. We are currently developing tools for analysis of segmental duplications, protein interaction data, and genomic

Recent Publications

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

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

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.

Wolfe, K. and W.-H. Li (2003)

Molecular evolution meets the genomics revolution. Nature Genetics Supplement 33: 255-265.

Yang, J., R. Lusk & W.-H. Li (2003)

Organismal complexity, protein complexity, and gene duplicability. Proc. Natl. Acad. Sci. USA. 100: 15661-15665.

Qin, H., H.H.S. Lu, W.B. Wu & W.-H. Li (2003)

Evolution of the yeast protein interaction network. Proc. Natl. Acad. Sci. USA. 100: 12820-12824.

Gu, Z., S. A. Rifkin, K. P. White, & W.H. Li (2004)

Duplicate genes increase gene expression diversity within and between Species. Nat. Genet 36, 577-579.

Yi, S., T. J. Summers, N. M. Pearson, & W.-H. Li (2004)

Recombination has little effect on the rate of sequence divergence in pseudoautosomal boundary 1 among humans and great apes. Genome Res. 14:37-43.