Phylogenetic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters

Abstract

BackgroundEver 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.ResultsSeven 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 cephalocordate sequences the time window when these duplications could have occurred is wider. All but two gene families also show teleost-specific duplicates.ConclusionBased 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.

Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula

“…In situ hybridization was performed on larval zebrafish and sections of adult brain and other tissues, as described previously (Westerfield, 1995). cRNA probes for adenylate cyclase activating polypeptide 1a (adcyap1a) (Fradinger and Sherwood, 2000), diamine oxidase (Sundström et al, 2008), hypothetical protein LOC335834, protocadherin 10a (pcdh10a) (Woods et al, 2005), pcdh10b (Murakami et al, 2006), and POU domain, class 4, transcription factor 1 (brn3a) (Aizawa et al, 2005) were used for the hybridization reaction. For double hybridizations, a digoxigenin-labeled probe for dao and fluorescein-labeled probe for pcdh10a were visualized with the TSA Plus System (PerkinElmer) and FastRed (Roche), respectively.…”

Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain

“…Finally, we assessed whether the presence of closely located H3K27me3 domains may promote and/or enhance the establishment of long-range interactions. Such an effect, if associated with a functional outcome, could have participated in the maintenance of paralogous syntenic relationships, such as the conserved clustering of Hox, Dlx, and Sp genes, which is found on multiple chromosomes and thus predates the 2R genome duplications that occurred at the root of the vertebrate lineage (23,24). In both ES and forebrain cells, significant K27 BRICKs are unequally distributed, with clusters of multiple K27 BRICKs being separated by large intervals of several megabases (Fig.…”

Aspartyl Aminopeptidase, Encoded by an Evolutionarily Conserved Syntenic Gene, Is Colocalized with Its Cluster in Secretory Granules of Pancreatic Islet Cells

“…Many homologous genes are clustered in genomes and evolutionarily conserved in syntenic segments cross-species, 1,2) including immunoglobulin genes 3) and chemosensory receptor genes. 4) As more genomes are sequenced, more syntenic clustered genes will be identified through comparative genomics, which will dramatically enhance understanding of the significance of functional genomes in the physiology and pathophysiology of life.…”