Dr. Wen-Hsiung Li

Evolutionary Biology, Genetics, Genomics

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.

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.

1. Liang H, Li WH. (2007) Gene essentiality, gene duplicability and protein connectivity in human and mouse. Trends Genet. 23(8):375-378
2. Shih AC, Hsiao TC, Ho MS, Li WH. (2007) Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution. Proc Natl Acad Sci U S A.104(15):6283-6288.
3. Hanada K, Zhang X, Borevitz JO, Li WH, Shiu SH. (2007) A large number of novel coding small open reading frames in the intergenic regions of the Arabidopsis thaliana genome are transcribed and/or under purifying selection. Genome Res. 17(5):632-640.
4. Saunders MA*, Liang H*, Li WH.(2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci U S A. 104(9):3300-5. [* equally contributed]
5. Ha M, Li WH, Chen ZJ. (2007) External factors accelerate expression divergence between duplicate genes. Trends Genet. 23(4):162-166.
6. Saunders MA, Good JM, Lawrence EC, Ferrell RE, Li WH, Nachman MW. (2006) Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth. Am J Hum Genet. 79(6):1089-1097.
7. Chen FC, Chen CJ, Li WH, Chuang TJ. Human-specific insertions and deletions inferred from mammalian genome sequences.(2007) Genome Res. 17(1):16-22.
8. Lin YS, Byrnes JK, Hwang JK, Li WH. (2006) Codon-usage bias versus gene conversion in the evolution of yeast duplicate genes. Proc Natl Acad Sci U S A.103(39):14412-14416.
9. Shiu SH, Byrnes JK, Pan R, Zhang P, Li WH. (2006) Role of positive selection in the retention of duplicate genes in mammalian genomes. Proc Natl Acad Sci U S A. 103(7):2232-2236.
10. Tan Y, Yoder AD, Yamashita N, Li WH. (2005) Evidence from opsin genes rejects nocturnality in ancestral primates. Proc Natl Acad Sci U S A. 102(41):14712-14716.
11. Tsai HK, Lu HH, Li WH. (2005) Statistical methods for identifying yeast cell cycle transcription factors. Proc Natl Acad Sci U S A. 102(38):13532-13537.
12. Li WH, Yang J, Gu X. (2005) Expression divergence between duplicate genes. Trends Genet. 21(11):602-607.
13. Li WH, Saunders MA. (2005) News and views: the chimpanzee and us. Nature 437(7055):50-51.
14. Gu Z, Rifkin SA, White KP, Li WH. (2004) Duplicate genes increase gene expression diversity within and between species. Nat Genet. 36(6):577-579.
15. Yi S, Summers TJ, Pearson NM, Li WH.(2004) Recombination has little effect on the rate of sequence divergence in pseudoautosomal boundary 1 among humans and great apes. Genome Res.14(1):37-43.