title: Interchromosomal segmental duplications explain the unusual structure of PRSS3, the gene for an inhibitor-resistant trypsinogen.
abstract: Homo sapiens possess several trypsinogen or trypsinogen-like genes of which three (PRSS1, PRSS2, and PRSS3) produce functional trypsins in the digestive tract. PRSS1 and PRSS2 are located on chromosome 7q35, while PRSS3 is found on chromosome 9p13. Here, we report a variation of the theme of new gene creation by duplication: the PRSS3 gene was formed by segmental duplications originating from chromosomes 7q35 and 11q24. As a result, PRSS3 transcripts display two variants of exon 1. The PRSS3 transcript whose gene organization most resembles PRSS1 and PRSS2 encodes a functional protein originally named mesotrypsinogen. The other variant is a fusion transcript, called trypsinogen IV. We show that the first exon of trypsinogen IV is derived from the noncoding first exon of LOC120224, a chromosome 11 gene. LOC120224 codes for a widely conserved transmembrane protein of unknown function. Comparative analyses suggest that these interchromosomal duplications occurred after the divergence of Old World monkeys and hominids. PRSS3 transcripts consist of a mixed population of mRNAs, some expressed in the pancreas and encoding an apparently functional trypsinogen and others of unknown function expressed in brain and a variety of other tissues. Analysis of the selection pressures acting on the trypsinogen gene family shows that, while the apparently functional genes are under mild to strong purifying selection overall, a few residues appear under positive selection. These residues could be involved in interactions with inhibitors.
authors.affiliation: Institute for Systems Biology, Seattle, Washington, USA. lrowen@systemsbiology.org
authors.forename: Lee
authors.initials: L
authors.lastname: Rowen
authors.forename: Eleanor
authors.initials: E
authors.lastname: Williams
authors.forename: Gustavo
authors.initials: G
authors.lastname: Glusman
authors.forename: Elena
authors.initials: E
authors.lastname: Linardopoulou
authors.forename: Cynthia
authors.initials: C
authors.lastname: Friedman
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Ahearn
authors.forename: Jason
authors.initials: J
authors.lastname: Seto
authors.forename: Cecilie
authors.initials: C
authors.lastname: Boysen
authors.forename: Shizhen
authors.initials: S
authors.lastname: Qin
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Amardeep
authors.initials: A
authors.lastname: Kaur
authors.forename: Scott
authors.initials: S
authors.lastname: Bloom
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Trask
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D006801:Humans; D040641:Quantitative Trait Loci / Q000235:genetics*; D012641:Selection, Genetic; D014357:Trypsin / Q000235:genetics*; D014361:Trypsin Inhibitors / Q000235:genetics*; D014362:Trypsinogen / Q000235:genetics*
chemical_list: D014361:Trypsin Inhibitors; D014362:Trypsinogen; C040749:PRSS3 protein, human; D014357:Trypsin