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Three insulin-relaxin-like genes in Ciona intestinalis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience. (Hallböök)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience. (Hallböök)
2006 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 27, no 11, 2535-2546 p.Article in journal (Refereed) Published
Abstract [en]

The Ciona intestinalis genome harbors three insulin-like genes: INS-L1, -L2 and -L3. Conserved synteny between the Ciona-human genomes predicts that Ciona INS-Ls are orthologous to the vertebrate insulin-relaxin family, but this relation cannot be inferred from molecular phylogeny. A conserved protein core with six cysteines; typical arrangement of B-, C- and A-protein domains; pro-protein maturation mode; and putative insulin receptor-binding sites were identified in Ciona INS-L proteins. ESTs used to assemble exonic sequences of INS-Ls combined with qRT-PCR analysis provided evidence that the predicted genes are expressed in the developing and adult Ciona. Our results support that Ciona INS-L1 is orthologous to the vertebrate insulin-like/relaxin genes, INS-L2 to insulin genies and INS-L3 to IGF genes. Our analysis also implies that the insulin-like/relaxin ancestor switched receptor type from tyrosine kinase- to GPCR-type, whereas insulin-IGF subfamily retained the tyrosine kinase-type of receptor. We propose that this receptor-switch occurred after the time when urochordates branched from the common chordate lineage, but before the two genome-duplications at the root of the vertebrates.

Place, publisher, year, edition, pages
2006. Vol. 27, no 11, 2535-2546 p.
Keyword [en]
Ciona intestinalis, gene duplication, IGF, insulin, insulin-like protein, relaxin
National Category
Medical and Health Sciences Biological Sciences
URN: urn:nbn:se:uu:diva-95914DOI: 10.1016/j.peptides.2006.06.008ISI: 000242318900001PubMedID: 16920224OAI: oai:DiVA.org:uu-95914DiVA: diva2:170291
Available from: 2007-05-11 Created: 2007-05-11 Last updated: 2012-03-09Bibliographically approved
In thesis
1. Evolutionary Analysis of the Insulin-Relaxin Gene Family from the Perspective of Gene and Genome Duplication Events
Open this publication in new window or tab >>Evolutionary Analysis of the Insulin-Relaxin Gene Family from the Perspective of Gene and Genome Duplication Events
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[pl]
Ewolucyjna Analiza Rodziny Genów Insulin-Relaksyn z Perspektywy Duplikacji Genu i Genomu
Abstract [en]

Paralogs arise by duplications and belong to families. Ten paralogs (insulin; IGF-1 and -2; INSL3-6 and 3-relaxins) constitute the human insulin-relaxin family. The aim of this study was to outline the duplications that gave rise to the vertebrate insulin-relaxin genes and the chromosomal regions in which they reside. Neurotrophin and Trk-receptor families with more than 300, otherwise unrelated, families had paralogs in the regions hosting insulin/relaxin genes, defining two quadruplicate paralogy-regions, namely: insulin/IGF and INSL/relaxin paralogons. Thereby, the localization of insulin/relaxins in human shows that these regions were formed during two genome duplications at the stem of the vertebrates.

We characterized insulin-like genes (INS-L1, -L2 and -L3) in the Ciona intestinalis genome, a species that split from the chordate lineage before the genome duplications. Conserved synteny between the Ciona region hosting the INS-Ls and two human paralogons as well as linkage of the actual paralogons, suggest that a segmental duplication gave rise to the entire region prior to the genome duplications. Synteny together with gene and protein structures demonstrate that INS-L1 is orthologous to the vertebrate INSLs/relaxins, INS-L2 to insulins and INS-L3 to IGFs. This indicates that pro-orthologs of the insulin-relaxin family were formed before Ciona. Our analysis also implies that the INSL/relaxin ancestor switched receptor from tyrosine kinase- to GPCR-type. This probably occurred after the Ciona-stage, but before the genome duplications.

Using genes residing within the analyzed human paralogons that were present in a chromosomal region in the Ciona-human ancestor, we identified 37 segments with conserved synteny between the Drosophila melanogaster and human genomes. Orthologs residing in Ciona-, sea urchin- and the fly syntenic segments imply that such segments approximate an ancestral region from which the human paralogons originated.

To conclude, the human paralogons are remnants of genome duplications that in addition to segmental- and single duplications, shaped the extant vertebrate genomes. Using the quadruplicate paralogy-regions we were able to deduce duplication events of the insulin-relaxin genes and their chromosomal regions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 70 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 260
Neurosciences, insulin, relaxin, insulin-like protein, gene duplication, paralogous region, Ciona intestinalis, conserved synteny, ortholog, Drosophila melanogaster, Neurovetenskap
urn:nbn:se:uu:diva-7892 (URN)978-91-554-6899-6 (ISBN)
Public defence
2007-05-31, B42, Biomedical center, Husargatan 3, 75123, Uppsala, 09:15
Available from: 2007-05-11 Created: 2007-05-11Bibliographically approved

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