| 1. Male mutation bias, or male-driven evolution. As the number of cell divisions is higher in the male germ line compared to the female germ line, the number of mutations originating in males is also higher than in females. The underlying assumption is that mutations are replication-driven. Y chromosome mutates faster than X, while autosomes have intermediate mutation rate. This is because Y is carried only by males, autosomes spend equal amount of time in males and females, and X spends 1/3 of time in males and 2/3 of time in females. Thus, by studying mutations on different types of chromosomes, one can investigate the male-to-female mutation rate ratio. The research focuses on estimating the male-to-female mutation rate ratio for different types of mutations (nucleotide substitutions, insertions and deletions, changes in the microsatellite repeat number) and for different organisms (primates, rodents as well as other mammals). This project is critical for genetic counseling (how important is the age of a male at the time of reproduction?) as well as for our understanding of mutation mechanisms. |
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| 2. Evolution of gene expression. While we now have some information about the evolution of the protein coding genes, there is a paucity of knowledge about evolution of gene expression. For instance, does the divergence in gene expression correlate with the protein sequence divergence? In other words, are the evolution of coding region and the evolution of mRNA expression coupled? One can have some insight into this question by analyzing the tempo of expression divergence between duplicate genes in a genome. A general picture is now achievable thanks to the advent of microarray gene expression technology and the complete sequences of many genomes. Another area of interest is population genetics and molecular evolution of promoters. |
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| The relationship between sequence divergence and the proportion of human gene pairs with diverged expression. (A) Synonymous divergence (KS) is used to represent sequence divergence. Each point represents 30 gene pairs. (B) Nonsynonymous divergence (KA) is used to represent sequence divergence. Each point represents 60 gene pairs. Solid diamonds represent the proportion of gene pairs with diverged expression in at least one tissue, and open diamonds represent proportion of gene pairs with diverged expression in at least two tissues. Solid and punctured lines are the corresponding linear regressions (from Makova and Li, Genome Research, 2003). |
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