<p>Paralogs arise by duplications and belong to families. Ten paralogs (insulin; <i>IGF-1</i> and <i>-2</i>; <i>INSL3-6</i> 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.</p><p>We characterized insulin-like genes (<i>INS-L1</i>, <i>-L2</i> and <i>-L3</i>) in the <i>Ciona intestinalis</i> genome, a species that split from the chordate lineage before the genome duplications. Conserved synteny between the Ciona region hosting the <i>INS-Ls</i> 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 <i>INS-L1</i> is orthologous to the vertebrate <i>INSLs</i>/relaxins, <i>INS-L2</i> to insulins and <i>INS-L3</i> to <i>IGFs</i>. 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.</p><p>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 <i>Drosophila melanogaster</i> 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.</p><p>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.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-7892 |
| Date | January 2007 |
| Creators | Olinski, Robert Piotr |
| Publisher | Uppsala University, Developmental Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 260 |
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