Chi-Hua Chiu Assistant Professor Departments of Genetics and Anthropology, Center for Human Evolutionary Studies

Evolutionary and Developmental Genetics Research

There is a growing awareness that recent advances in evolutionary genomics and developmental genetics can provide significant insights into evolution and the nature of biodiversity. This is the central theme of research in my lab.

In one area of study, we use evolution-based strategies for investigating how molecular processes such as gene duplication and regulatory element (enhancer) evolution have shaped the genomes of higher organisms (e.g. human and zebrafish). The P.I. has used this approach for understanding evolution of regulation of the beta-type globin gene cluster in mammals. The lab currently focuses on the HOX genes, which originated early in metazoan phylogeny and are distributed throughout the animal kingdom. HOX genes, which encode transcription factors that play an important role in embryonic development, are organized in clusters in the genome. These clusters display tandem gene duplication, gene loss, gene sequence divergence, functional divergence, and regulatory element evolution. HOX clusters also display the phenomenon of colinearity, in which the position of a gene in the cluster is related to its expression dynamics in the developing embryo. The study of HOX genes, therefore, provides the opportunity to understand the relationship between genome organization and gene expression. Finally, the lab is initiating projects which will focus on identifying and tracing through primate phylogeny the functionally important regulatory mutations of genes involved in cognitive disorders in humans, especially genes that act early in brain development.  This research involves large scale DNA sequencing, evolutionary sequence analysis, the construction and screening of large-insert BAC or PAC genomic libraries as well as recombinogenic methods for modifying BAC/PAC large-insert clones for expression studies. Taxa of interest include fish (zebrafish, bichir), mouse, and different primate lineages (galago, baboon, apes, human).

The second and related area of study is evolutionary developmental biology or "evo-devo", which seeks to explain the evolution and development of morphological characters as well as the evolution of their underlying genetic and developmental mechanisms using a comparative approach. We currently use the tetrapod limb as a model system, with focus on the genetic basis for evolutionary diversity in the hands and feet of primates. This research combines developmental biology methodologies using traditional animals models such as mouse and chick with functional tests (e.g. transgenic expression assays) in order to identify sequence changes in developmental patterning and growth genes that are associated with interspecific differences in adult primate limb morphologies.

Selected Publications

Wagner GP, Chiu C-H. 2001. The tetrapod limb: A definition and a hypothesis on its origin. Mol Dev Evol, in press.

Chiu C-H, Nonaka D, Xue L, Amemiya CT, Wagner GP. 2000. Evolution of Hoxa-11 in lineages phylogenetically positioned along the fin-limb transition. Mol Phyl Evol 17: 305-316.

Chiu C-H, Amemiya CT, Carr JL, Bhargava J, Hwang JK, Shashikant CS, Ruddle FH, Wagner GP. 2000. A recombinogenic targeting method to modify large-inserts for cis-regulatory analysis in transgenic mice: construction and expression of a 100-kb, zebrafish Hoxa-11b-lacZ reporter gene. Dev Genes Evol 210: 105-109.

Wagner GP, Chiu C-H, Laubichler M. 2000. Developmental evolution as a mechanistic science: The inference from developmental mechanisms to evolutionary processes. Amer Zool 40: 819-831.

Hansen TF, Carter A, Chiu C-H. 2000. Gene conversion may aid adaptive peak shifts. Journal of Theoretical Biology 207: 495-511.

Chiu C-H, Schneider H, Slightom JL, Gumucio DL, Goodman, M. 1997. Dynamics of cis-regulatory evolution in primate beta-globin gene clusters: Cis-mediated acquisition of simian gamma fetal expression patterns. Gene 205: 47-57.

Chiu C-H, Schneider H, Schneider MPC, Sampaio I, Meireles C, Slightom JL, Gumucio DL, Goodman M. 1996. Reduction of two functional gamma-globin genes to one: An evolutionary trend in New World monkeys (Infraorder Platyrrhini). Proc Natl Acad Sci USA 93: 6510-6515.