Genomic studies on gene duplication.

Abstract

Using yeast <italic>Saccharomyces cerevisiae</italic> as the main model organism, I addressed three fundamental questions on gene duplication. I first investigated the functional divergence after gene duplication, revealing a general pattern of rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in the evolution of duplicate genes, which leads to a new model termed sub-neo-functionalization. I then examined the factors that could affect gene duplicability. Consistent with the sub-neo-functionalization model, I showed that complex genes are preferentially duplicated in yeast genomes, and that duplicate genes have longer protein sequences, more functional domains, and more <italic>cis</italic>-regulatory motifs than singleton genes. Thus, gene duplication increases both gene number and average gene complexity, two important factors in the origin of genomic and organismal complexity. In the last part of the thesis I evaluated the hypothesis of functional compensation between duplicate genes, which is the prevailing explanation for the phenotypic discrepancy between deleting a singleton gene and deleting a duplicate gene. After thoroughly analyzing all available functional data, I failed to find unequivocal evidence for the compensation hypothesis. Instead, old duplicates were found to have similar levels of phenotypic effects as singletons. The smaller phenotypic effect of deleting a young duplicate than deleting a singleton is primarily due to preferential duplication of less important genes and dilution of essentiality after duplication by subfunctionalization. My work highlights the strength of comparative functional genomics in evolutionary studies, and provides new views on the evolution of duplicate genes.