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Phylogenetic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology. (Larhammar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology. (Larhammar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology. (Larhammar)
2008 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, Vol. 8, 254- p.Article in journal (Other academic) Published
Abstract [en]


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.


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


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.

Place, publisher, year, edition, pages
2008. Vol. 8, 254- p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-96167DOI: 10.1186/1471-2148-8-254ISI: 000260127200001PubMedID: 18803835OAI: oai:DiVA.org:uu-96167DiVA: diva2:170647
Available from: 2007-09-07 Created: 2007-09-07 Last updated: 2014-11-13Bibliographically approved
In thesis
1. Evolution of the Neuropeptide Y System in Vertebrates with Focus on Fishes
Open this publication in new window or tab >>Evolution of the Neuropeptide Y System in Vertebrates with Focus on Fishes
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gene families in vertebrates often contain more dulicates (paralogs) than in invertebrates. This has been attributed to genome duplications, i.e., tetraploidizations. Two of the gene families that have expanded in vertebrate evolution are the neuropeptide Y (NPY) family of peptides and the neuropeptide Y receptors (NPYR) that are involved in many brain functions including appetite regulation.

Two NPYR genes, Y2 and Y7, were cloned in the rainbow trout. Although they arose from a common ancestral gene in early vertebrate evolution, their ligand-binding properties are very similar. Two NPYR genes were cloned in the coelacanth Latimeria chalumnae and found to be orthologs of Y5 and Y6 discovered in mammals.

Analyses of gene families close to the NPYR genes in the pufferfishes T. nigroviridis and T. rubripes showed that at least 25 additional gene families had an evolutionary history similar to the NPYR family, thereby providing evidence for fish specific-duplications of these chromosomes. Cloning and phylogenetic analysis of 22 NPYR gene fragments from several ray-finned fishes showed that basal species seem to have the same repertoire as tetrapods. Despite the tetraploidization in the teleost fish lineage, many teleosts seem to have fever genes than the gnathostome ancestor due to gene loss. Only one duplicate seems to have survived.

The NPY peptide family was found to have expanded in the teleost tetraploidization with duplicates of both NPY and PYY (peptide YY) in some teleosts. Fourteen neighboring gene families were found to have evolved in a similar manner as the NPY-family genes. Positional information fascilitated orthology assignment of peptide genes in teleost fishes and allowed correction of previously misidentified genes.

In summary, the evolutionary history of the NPY and NPYR gene families involve large-scale duplication events coinciding with the proposed tetraploidizations. The appearance of new genes in early vertebrates and in teleost fishes probably had important implications for the evolution of new functions in this system.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 272
Molecular biology, neuropeptide Y, GPCR, evolution, gene duplication, vertebrates, ray-finned fishes, Molekylärbiologi
urn:nbn:se:uu:diva-8189 (URN)978-91-554-6958-0 (ISBN)
Public defence
2007-09-28, B22, BMC, Husargatan 3, Uppsala, 10:15
Available from: 2007-09-07 Created: 2007-09-07Bibliographically approved

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