title: Evolution of Hoxa-11 in lineages phylogenetically positioned along the fin-limb transition.
abstract: HOXA11 is a transcription factor implicated in paired appendage development. To identify signatures of evolutionary change in the structural, and putative functional, domains of HOXA11, we studied its evolution in tetrapod and nontetrapod lineages that represent approximately 1.5 billion years of evolutionary time. Here, Hoxa-11 gene proper sequences were determined for frog (Xenopus tropicalis), coelacanth (Latimeria chalumnae), common zebrafish (Danio rerio; Hoxa-11a and Hoxa-11b paralogs), and giant zebrafish (D. aequipinnatus; Hoxa-11b) and aligned against previously published Hoxa-11 sequences of human, mouse, chick, and newt. Based on aligned Hoxa-11 amino acid sequences, the protein was demarcated into three segments: Domains I (N-terminal) and III (homeobox + C-terminal), which varied slightly in rates and patterns of evolution, and a variable, overall hydrophilic region (HyD), which partially overlaps with Domain I. As judged by character reconstructions of HOXA11 Domains I and III, no significant changes in rates of coding sequence evolution occurred in tetrapods (frog and chick), relative to coelacanth (a lobe-finned fish), i.e., across the fin-limb transition. Accelerated rates of Hoxa-11 coding sequence evolution were observed for the mammalian and newt lineages. This was shown to be a gene-specific phenomenon. The duplicated Hoxa-11a and Hoxa-11b genes of zebrafish exhibited accelerated rates of evolution and accumulated substitutions at sites that are conserved among coelacanth and all tetrapods examined. Amino acid sequence comparisons of the HyD of HOXA11 suggested that a putative repressor subdomain, containing stretches of consecutive alanine residues, emerged within the tetrapods. A high degree of nucleotide conservation in the 5' half of the Hoxa-11 intron was observed for tetrapod and nontetrapod lineages. Using electrophoretic mobility shift assays, a 35-bp intron sequence, which is 100% conserved in all Hoxa-11 loci except for the zebrafish Hoxa-11a paralog, was found to bind protein(s) in HeLa and chick whole-cell extracts.
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520-8106, USA. chi-hua.chiu@yale.edu
authors.forename: C H
authors.initials: CH
authors.lastname: Chiu
authors.forename: D
authors.initials: D
authors.lastname: Nonaka
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: C T
authors.initials: CT
authors.lastname: Amemiya
authors.forename: G P
authors.initials: GP
authors.lastname: Wagner
mesh_terms: D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005121:Extremities; D005399:Fishes / Q000235:genetics; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014981:Xenopus / Q000235:genetics; D029867:Xenopus Proteins; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins
chemical_list: C105337:HOXA11 protein, Xenopus; C484298:HOXA11 protein, human; D018398:Homeodomain Proteins; C094041:Hoxa11 protein, mouse; D020033:Protein Isoforms; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C491345:hoxa11a protein, zebrafish; C491346:hoxa11b protein, zebrafish; D004247:DNA; D000409:Alanine