title: Phylogenetic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters.
abstract: BACKGROUND
  Ever since the theory about two rounds of genome duplication (2R) in the vertebrate lineage was proposed, the Hox gene clusters have served as the prime example of quadruplicate paralogy in mammalian genomes. In teleost fishes, the observation of additional Hox clusters absent in other vertebrate lineages suggested a third tetraploidization (3R). Because the Hox clusters occupy a quite limited part of each chromosome, and are special in having position-dependent regulation within the multi-gene cluster, studies of syntenic gene families are needed to determine the extent of the duplicated chromosome segments. We have analyzed in detail 14 gene families that are syntenic with the Hox clusters to see if their phylogenies are compatible with the Hox duplications and the 2R/3R scenario. Our starting point was the gene family for the NPY family of peptides located near the Hox clusters in the pufferfish Takifugu rubripes, the zebrafish Danio rerio, and human.
  
  
  RESULTS
  Seven of the gene families have members on at least three of the human Hox chromosomes and two families are present on all four. Using both neighbor-joining and quartet-puzzling maximum likelihood methods we found that 13 families have a phylogeny that supports duplications coinciding with the Hox cluster duplications. One additional family also has a topology consistent with 2R but due to lack of urochordate or cephalochordate sequences the time window when these duplications could have occurred is wider. All but two gene families also show teleost-specific duplicates.
  
  
  CONCLUSIONS
  Based on this analysis we conclude that the Hox cluster duplications involved a large number of adjacent gene families, supporting expansion of these families in the 2R, as well as in the teleost 3R tetraploidization. The gene duplicates presumably provided raw material in early vertebrate evolution for neofunctionalization and subfunctionalization.
authors.affiliation: Department of Neuroscience, Uppsala University, Box 593, 75124 Uppsala, Sweden. Gorel.Sundstrom@neuro.uu.se
authors.forename: Görel
authors.initials: G
authors.lastname: Sundström
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Larsson
authors.forename: Dan
authors.initials: D
authors.lastname: Larhammar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D020440:Gene Duplication; D005801:Genes, Homeobox; D006801:Humans; D005810:Multigene Family; D009478:Neuropeptide Y / Q000235:genetics*; D010802:Phylogeny; D016415:Sequence Alignment; D023741:Takifugu / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
chemical_list: D009478:Neuropeptide Y