Comparative genomics on the vertebrate ParaHox gene cluster. (360G-Wellcome-081233_Z_06_Z)

The clustered Hox genes comprise only 39 of the > 200 homeobox genes in the human genome. The non-Hox homeobox genes are usually studied in isolation, butin fact some are in gene clusters. We found that three (Gsx, Xlox/Pdx, Cdx) form the ParaHox cluster in amphioxus, human, mouse, Xenopus and basal ray-finned fish, but not in zebrafish and pufferfish (where the constituent genes have dispersed). We will use a combination of comparative genomics and experimental assays to ask: (1) How conserved is the ParaHox gene cluster? Totest, we will analyse two species chosen for their positions in vertebrate diversity. (2) When, how and why did the ParaHox cluster disintegrate in teleost fish evolution? We hypothesize that whole genome duplication (WGD) at the base of the teleosts allowed interdigitated ParaHox genes to be dissociated. We will test by comparison between fish branching before and after the WGD, including zebrafish and some non-traditional models. (3) What is the functional reason for the cluster? We hypothesize the genes are trappedby shared enhancers and overlapping gene organisation; we will test this by determining the activity of conserved non-coding regions using Xenopus transgenics. (4) What are the implications for zebrafish as a model?