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Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2008 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, Vol. 8, no 1, 184- p.Article, review/survey (Refereed) Published
Abstract [en]


One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY) receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes) and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10.


Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs) showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains) and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events). RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs.


We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate tetraploidizations forming a paralogon comprising human chromosomes 4, 5, 8 and 10 and one teleost tetraploidization. The combination of positional and phylogenetic data further strengthens the identification of orthologs and paralogs in the NPY receptor family.

Place, publisher, year, edition, pages
2008. Vol. 8, no 1, 184- p.
National Category
URN: urn:nbn:se:uu:diva-96164DOI: 10.1186/1471-2148-8-184ISI: 000257683600001PubMedID: 18578868OAI: oai:DiVA.org:uu-96164DiVA: diva2:170644
Available from: 2007-09-07 Created: 2007-09-07 Last updated: 2011-01-13Bibliographically 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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