Wen-Hsiung Li
Academia Sinica
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Primary Section: 27, Evolutionary Biology Secondary Section: 26, Genetics Membership Type:
Member
(elected 2003)
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Research Interests
I have been interested in molecular evolution and evolutionary genomics. There are currently two main projects going on the lab. I. Evolution of regulatory modules and networks The significance of regulatory evolution has been recognized since the 1960s. For example, the conspicuous morphological differences between humans and chimpanzees were suggested to be mainly due to regulatory differences between the two species. However, regulatory evolution has not been much studied in the past mainly because of scarcity of suitable data. Fortunately, advances in molecular biology and genomics in recent years have enabled one to study not only the regulation of single genes, but also the co-regulation of many genes. Thus, one can now pursue detailed investigation of regulatory evolution, including the evolution of regulatory modules, which are sets of co-regulated genes, and will soon be able to study the evolution of the entire regulatory network in closely related eukaryotes. To pursue this project we are using both theoretical and experimental approaches. First, we are developing methods for inferring regulatory modules from microarray data and real time PCR data and for comparing data from different strains or species. The purposes are to infer which genes are on the same module and how modules interact, and to understand how modules diverge between strains or species. Second, we are using yeast as a model organism to obtain microarray data and real time PCR data for the above purposes. II. Evolution of duplicate genes at the genomic level Since Ohno (1970) it has been commonly believed that gene duplication is the primary source of genetic novelties. In the past, however, the study of the evolution of duplicate genes had relied mainly on isozyme data. Taking advantage of the availability of genomic sequence data and functional genomic data, we have been pursuing this topic at the genomic level, e.g, developing methods for detecting duplicate genes in a genome and for estimating the rate of gene duplication in a genome. Our current interests are: (1) The mode and tempo of expression divergence between duplicate genes. We are using microarray and other data to study how often and how fast duplicate genes diverge in expression, because regulatory divergence is commonly thought to be the first step for functional divergence between duplicate genes. (2) Determinants of gene duplicability. What factors determine the retention of both copies of duplicate genes in a genome? We are studying such factors as function, protein complexity (number of subunits in a protein), organismal complexity, etc. (3) The role of duplicate genes in the genetic robustness against null mutation. The deletion or knockout of a gene often shows no discernible phenotypic effect. Is this mainly due to the existence of duplicate genes or due to alternative pathways?
