There is a growing awareness that recent advances in developmental genetics and in complex systems theory, both, will fundamentally change how we think about the evolution of higher organisms. This is also the focus of the research in my lab. The lab consists of a group of theorists, who use mathematical modeling to understand complex adaptations, and a group of molecular and developmental biologists, using comparative sequencing and transgenic techniques to understand the evolution of developmental control genes. The emphasis of the molecular group is on the molecular evolution of Hox genes and their role in the origin and early evolution of tetrapod limbs. Tetrapod limbs are both an important complex adaptation of terrestrial vertebrates and as well as one of the best known developmental model systems from vertebrates. The focus of our mathematical work is on the dynamics of complex adaptations and the evolution of the so-called genotype-phenotype map, i.e. the way how genetic changes relate to phenotypic changes. This requires us to develop new modeling techniques, like the theory of recombination landscapes and the modeling of gene interactions. Another goal is to understand the mechanisms causing the evolution of a modular representation of the phenotype.
Extensive Research Description
Evolution of gene regulation in endometrial stromal cells:
We study the gene regulatory network of endometrial stomal cells and how it evolved. In particular we are interested in the role of transposable elements in providing novel cis-regulatory elements and in the role of transcription factor protein changes to allow the regulation of novel target genes.
Evolution of human parturition and spontaneous decidualization (menstruation):
Humans and higher primates are distinct from most other mammals in that 1) the endometrium differentiates each reproductive cycle even in the absence of a conceptus, and 2) parturition is initiated without systemic progesterone withdrawal. Interestingly these two characteristics are taxonomically co-extensive, i.e. are only found in humans and higher primates. In my lab we try to understand the genetic changes underlying both phenomena. This research is in collaboration with the NIH Perinatology Research Branch at Wayne State University, Detroit, MI.
Evolution of digit identity in birds:
The identity of the three definite digits in the bird wing is a longstanding problem in comparative anatomy. The problem is that these digits have the structure of digits 1, 2, and 3, but develop from embryonic positions 2, 3, and 4. In 1999 my colleague Jacques Gauthier and I proposed that this occurred because of a homeotic digit identity frameshift during the evolution of dinosaurs. Gene expression evidence supports this hypothesis and now we are working towards identifying the genetic changes which gave rise to the digit identity frame shift.
- Wagner, G.P. (2007). The developmental genetics of homology. Nat. Rev. Genet. (6):473-9.
- Lynch, V. J., A. Tanzer, Y. Wang, F. C. Leung, B. Gellersen, and G. P. Wagner 2008 Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals. Proc. Natl. Acad. Sci. USA, 105:14928-14933.
- Wagner, G. P., J. P. Kenny-Hunt, M. Pavlicev, J. R. Peck, D. Waxman and J. Cheverund 2008. Pleiotropic scaling of gene effects an the “cost of complexity.” Nature, 452: 470-472.
- Otto, W., P. F. Stader, F. López-Gialdéz, J. P. Townsend, V. J. Lynch, and G. P. Wagner 2009. Measuring transcription factor binding site turnover: a maximum likelihood approach using phylogenies. Genome Biology and Evolution, 1:85-98.
- Vargas, A. O. and G. P. Wagner 2009. Cartilage formation and digit identity in bird evolution and Cyclopamine-treated wings. Evolution and Development, 11:163-169.
- Wagner, G. P., and V. J. Lynch 2008 The Gene regulatory logic of transcription factor evolution. Trends in Ecology and Evolution, 23: 377-385.
- Wagner, G. P., M. Pavlicev and J. Cheverud 2007. The road to modularity. Nature Reviews Genetics, 8:921-931.
- Wagner, GP, W. Otto, V. Lynch, and PF Stadler 2007. A stochastic model for transcription factor binding site abundance. J. theor, Biol., 247:544-553.
- Kohlsdorf, T and G. P. Wagner 2006 Evidence for the reversibility of digit loss: a phylogenetic study of limb evolution in the genus Bachia (Gymnophthalmidae: Squamata). Evolution 60: 1896-1912.
- Crow K. D., Stadler PF, Lynch V, Amemiya C, Wagner GP (2006) The “fish specific” Hox cluster duplication is coincidental with the origin of teleosts. Mol Biol. & Evol, 23:121-136.
- Wagner, G. P., and J. Gauthier 1999. 1,2,3 = 2,3,4: a solution to the problem of the homology of the digits in the avian hand. Proc. Natl. Acad. Sci. USA, 96, 5111-5116.