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Evolution of the neuropeptide Y family: new genes by chromosome duplications in early vertebrates and in teleost fishes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Larhammar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2008 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 155, no 3, 705-716 p.Article in journal (Refereed) Published
Abstract [en]

Despite sequence information from many vertebrates the evolution of the neuropeptide Y (NPY) family of peptides has been difficult to resolve, particularly among ray-finned fishes. We have used chromosomal location and sequence analyses to identify orthologs and gene duplicates in teleost fish genomes. Our analyses support origin of NPY and peptide YY (PYY) from a common ancestor in early vertebrate evolution through a chromosome duplication. We report here that the teleost tetraploidization generated duplicates of both NPY and PYY and that all four genes are still present in the two sequenced pufferfish genomes Tetraodon nigroviridis and Takifugu rubripes as well as three-spined stickleback, Gasterosteus aculeatus. The zebrafish Danio rerio NPYb gene has probably been lost whereas medaka, Oryzias latipes seems to lack PYYb. Some of the previously published PYY sequences were misidentified and actually constitute NPYb. Our analyses confirm that the peptide previously named PY in some fish species is a duplicate of the PYY gene and hence should be called PYYb. The NPYa and NPYb genes in Takifugu rubripes are predominantly expressed in brain, as detected by RT-PCR, whereas PYYa and PYYb are expressed in several organs including brain, intestine and gonads. Thus, also the resemblance in expression pattern supports the fish gene duplication scenario. Our study shows that when sequence comparisons give ambiguous results, chromosomal location can serve as a useful criterion to identify orthologs. This strategy may help to resolve relationships in several families of short peptides.

Place, publisher, year, edition, pages
2008. Vol. 155, no 3, 705-716 p.
Keyword [en]
tetraploidization, gene duplication, synteny, neuropeptide Y
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-96166DOI: 10.1016/j.ygcen.2007.08.016ISI: 000253272800027OAI: oai:DiVA.org:uu-96166DiVA: diva2:170646
Available from: 2007-09-07 Created: 2007-09-07 Last updated: 2010-09-29Bibliographically 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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