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Our main interest is in the evolutionary and population genetics of speciation and species differentiation, especially at the molecular level. It has also become clear recently that genome-level analyses will complement, and may eventually supplant, the gene-by-gene approach to the question of speciation. The interconnected subjects in this general area are studied in my laboratory as described below:
I. Molecular characterization of the Odysseus gene of speciation (Ods) - This speciation gene we cloned previously (Ting et al. 1998, 2000) causes hybrid male sterility between sibling species of Drosophila. It is a member of the homeobox gene family and has undergone a recent shift from neural to spermatogenic function. As a result, its rate of evolution has been elevated by 100 - 1000 fold. We are investigating: i) the expression patterns of Ods in related Drosophila species by antibody staining; ii) the detailed molecular function by germline transformation and site-directed mutagenesis; iii) the genetic pathway up- and downstream of Ods by genetical and biochemical means; and iv) the long term evolution and short term population genetics of Ods sequences.
II. To systematically investigate the molecular basis of speciation, both within and beyond the Drosophila melanogaster clade, we are currently exploring experimental approaches that may lead to large-scale transgenic studies among even distantly-related species. Recombination machinery of yeast is the main tool of choice when applied to Drosophila.
III. Genetic analysis of behavioral isolation between Drosophila races - This is a system of incipient speciation and is in a species most amenable to genetic analysis, D. melanogaster (Wu et al. 1995; Hollocher et al. 1997a, b). The goal is to complete the high-resolution mapping of genes controlling male and female mating preferences and to analyze the correlation between the two sets of genes. Molecular cloning of these genes is a long term goal.
IV. Molecular basis of natural and sexual selection - Genetic analyses have shown that speciation and species differentiation are driven, to a surprising extent, by sexual selection (Wu and Davis 1993; Wu et al. 1996; Ting et al. 1998). We are using a site-specific gene insertion technique to study the mechanism(s) of selection on an accessory gland protein (Acp) gene in Drosophila. This gene has been suggested by DNA sequence analysis to have evolved rapidly (Tsaur et al. 1997, 1998, 2001), presumably under the strong influence of sexual selection.
V. Genomic analysis (Data) - We are taking advantage of the explosion of DNA sequences in the data bank. A first example is the analysis of the patterns and forces governing the evolutionary rate of male reproductive genes between human and higher primates (Wyckoff et al. 2000). It is almost certain that sexual selection has played a dominant role in shaping the divergence and polymorphism in the genomes of higher primates.
VI Genomic analysis (Theory) - We are formulating theories to model the influence of positive Darwinian selection on the level and pattern of DNA variation in human and Drosophila populations (Fay and Wu 2000, Fay et al. 2001). While human data have been analyzed mainly to extract the historical information, future direction is likely to focus more and more on the dynamic processes driven by Darwinian selection (for example, how the infectious diseases and diet changes associated with agriculture might have affected the spread of advantageous genetic variants).
Finally, students and postdoctoral fellows are strongly encouraged to develop their own projects in the general area of evolutionary genetics.
Selected publications from the Wu laboratory in the last 5 year's
Tsaur, S. C., and C.-I Wu, 1997 Positive selection and the molecular evolution of a gene of male reproduction. Molec. Biol. Evol. 14:544-549.
Hollocher, H., C.-T. Ting, F. Pollack and C.-I Wu, 1997 Incipient speciation by sexual isolation in Drosophila melanogaster : Variation in mating preference among antural isolates. Evolution 51: 1175-1181.
Hollocher, H., C.-T. Ting, M.-L. Wu and C.-I Wu, 1997 Incipient speciation by sexual isolation in Drosophila melanogaster : Extensive divergence without reinforcement. Genetics 147: 1191-1201.
Tsaur, S. C., C.-T. Ting and C.-I Wu, 1998 Positive selection and the molecular evolution of a gene of male reproduction, Acp26Aa of Drosophila: II. Divergence vs. polymorphism. Molec. Biol. Evol. 15:1040 - 1046.
Wu, C.-I., and H. Hollocher, 1998 Subtle is nature: the genetics of species differentiation and speciation, pp.339-351 in Endless forms: species and speciation, edited by D. Howard and S. Berlocher. Oxford University Press.
Ting, C.-T., S.-C. Tsaur, M.-L. Wu and C.-I Wu, 1998 A rapidly evolving homeobox at the site of a hybrid sterility gene. Science 282: 1501-1504.
Fay, J. C. and C.-I Wu, 1999 A human population bottleneck is not incompatible with the discordance between patterns of mitochondrial vs. nuclear DNA variation. Molec. Biol. Evol. 16:1003 - 1006.
Wyckoff, G. J., W. Wang and C.-I Wu, 2000 Rapid evolution of male reproductive genes in the descent of man. Nature 403: 304 - 309.
Sawamura, K., A. W. Davis and C.-I Wu, 2000 Genetic analysis by means of introgression into Drosophila melanogaster. Proc. Natl. Acad. Sci. 97:2652-2655.
Ting, T.-C., S. C. Tsaur, S.-C., and C.-I Wu, 2000 The phylogeny of closely related species as revealed by the genealogy of a speciation gene, Odysseus. Proc. Natl. Acad. Sci. 97:5313 - 5316.
Fay, J. C. and C.-I Wu, 2000 Hitchhiking under positive Darwinian selection. Genetics 155: 1405-1413.
Wu, C.-I, 2000 Genetics of species differentiation: What is unknown and what will be unknowable? Evol. Biol. 32: 239 - 248. (M. T. Clegg, M. K. Hecht and R. J. MacIntyre, eds.)
Tsaur, S. C., C.-T. Ting and C.-I Wu, 2001 Sex in Drosophila mauritiana: Extremely high level of replacement polymorphism in a male reproductive gene. Molec. Biol. Evol. 18:22-26
Alipaz, J. A., C-I Wu and T. L. Karr, 2001 Sperm-egg incompatibility between races of Drosophila. Proc. Roy. Soc. 268:789-795.
Takahashi, A, S.C. Tsaur, J. A. Coyne and C.-I Wu, 2001 The nucleotide changes governing pheromonal variation in Drosophila and their evolution. Proc. Natl. Acad. Sci.98:3920-3925.
Fay, J. C., G. J. Wyckoff and C.-I Wu, 2001 Positive and negative selection on the human genome. Genetics 158:1227-1234.
Ting, C.T., A. Takahashi and C.-I Wu, 2001 Incipient speciation by sexual selection: concurrent evolution at multiple loci. Proc. Natl. Acad. Sci. 98: 6709-6713 (see also Nature 412:31-32)
Luo, Z.W. and C.-I Wu, 2001 Modeling linkage disequilibrium between a polymorphic marker locus and a locus affecting dichotomous disease traits in natural populations. Genetics 158: 1785-1800.
Wu, C.-I 2001 The genic view of the process of speciation. J. Evol. Biol. 14: 851-865..
Wu, C.-I 2001 Genes and Speciation - A reply. J. Evol. Biol. 14:889-891.
Fay, J. C. and C.-I Wu, 2001 The neutral theory in the genomic era. Curr. Opinion Gen. Dev. 11:642-646.
Fay, J. C., G. J. Wyckoff and C.-I Wu, 2002 Testing the neutral theory of molecular evolution with genomic data. Nature 415: 1024 - 1026.
Luo, Z.W., C.-I Wu, and M. J. Kearsey, 2002 Precision and high-resolution mapping of quantitative trait loci by use of recurrent selection, backcross or intercross schemes. Genetics 161: 915-929.
Wyckoff, G. J., J. Li and C.-I Wu, 2002 Molecular evolution of functional genes on the mammalian Y chromosome. Molec. Biol. Evol. (in press)
Fang, S., A. Takahashi, and C.-I Wu, 2002 A mutation in the promoter of desaturase 2 is correlated with sexual isolation between Drosophila behavioral races. Genetics (in press)