title: Evolutionary history and adaptive significance of the polymorphic Pan I in migratory and stationary populations of Atlantic cod (Gadus morhua).
abstract: The synaptophysin (SYP) family comprises integral membrane proteins involved in vesicle-trafficking events, but the physiological function of several members has been enigmatic for decades. The presynaptic SYP protein controls neurotransmitter release, while SYP-like 2 (SYPL2) contributes to maintain normal Ca(2+)-signaling in the skeletal muscles. The polymorphic pantophysin (Pan I) of Atlantic cod shows strong genetic divergence between stationary and migratory populations, which seem to be adapted to local environmental conditions. We have investigated the functional involvement of Pan I in the different ecotypes by analyzing the 1) phylogeny, 2) spatio-temporal gene expression, 3) structure-function relationship of the Pan I(A) and I(B) protein variants, and 4) linkage to rhodopsin (rho) recently proposed to be associated with different light sensitivities in Icelandic populations of Atlantic cod. We searched for SYP family genes in phylogenetic key species and identified a single syp-related gene in three invertebrate chordates, while four members, Syp, Sypl1, Sypl2 and synaptoporin (Synpr), were found in tetrapods, Comoran coelacanth and spotted gar. Teleost fish were shown to possess duplicated syp, sypl2 and synpr genes of which the sypl2b paralog is identical to Pan I. The ubiquitously expressed cod Pan I codes for a tetra-spanning membrane protein possessing five amino acid substitutions in the first intravesicular loop, but only minor structural differences were shown between the allelic variants. Despite sizable genomic distance (>2.5 Mb) between Pan I and rho, highly significant linkage disequilibrium was found by genotyping shallow and deep water juvenile settlers predominated by the Pan I(A)-rho(A) and Pan I(B)-rho(B) haplotypes, respectively. However, the predicted rhodopsin protein showed no amino acid changes, while multiple polymorphic sites in the upstream region might affect the gene expression and pigment levels in stationary and migratory cod. Alternatively, other strongly linked genes might be responsible for the sharp settling stratification of juveniles and the different vertical behavior patterns of adult Atlantic cod.
authors.affiliation: Nofima, P.O. Box 5010, N-1430 Ås, Norway; Department of Animal and Aquaculture Sciences, University of Life Sciences, P.O. Box 5003, N-1430 Ås, Norway. Electronic address: oivind.andersen@nofima.no.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Andersen
authors.affiliation: Nofima, Muninbakken 9-13, N-9291 Tromsø, Norway. Electronic address: hanne.johnsen@nofima.no.
authors.forename: Hanne
authors.initials: H
authors.lastname: Johnsen
authors.affiliation: Institute of Chemistry of Molecular Recognition-CNR and Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, 00168 Rome, Italy. Electronic address: mariacristina.derosa@icrm.cnr.it.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: De Rosa
authors.affiliation: Department of Arctic and Marine Biology, UiT The Arctic University of Norway, N-9037 Tromsø, Norway. Electronic address: kim.praebel@uit.no.
authors.forename: Kim
authors.initials: K
authors.lastname: Præbel
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, S-75007 Uppsala, Sweden. Electronic address: suzana.stjelja@gmail.com.
authors.forename: Suzana
authors.initials: S
authors.lastname: Stjelja
authors.affiliation: Department of Animal and Aquaculture Sciences, University of Life Sciences, P.O. Box 5003, N-1430 Ås, Norway. Electronic address: tina.graceline@nmbu.no.
authors.forename: Tina Graceline
authors.initials: TG
authors.lastname: Kirubakaran
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, 00168 Rome, Italy. Electronic address: davide.pirolli@rm.unicatt.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Pirolli
authors.affiliation: Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, P.O. Box 1066 Blindern, N-0316 Oslo, Norway. Electronic address: sissel.jentoft@ibv.uio.no.
authors.forename: Sissel
authors.initials: S
authors.lastname: Jentoft
authors.affiliation: Department of Arctic and Marine Biology, UiT The Arctic University of Norway, N-9037 Tromsø, Norway. Electronic address: svein-erik.fevolden@uit.no.
authors.forename: Svein-Erik
authors.initials: SE
authors.lastname: Fevolden
mesh_terms: D063147:Animal Distribution / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D019295:Computational Biology; D019143:Evolution, Molecular; D005260:Female; D048389:Gadus morhua / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D005828:Genetics, Population; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012243:Rhodopsin / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity; D016708:Synaptophysin / Q000235:genetics*
chemical_list: D016708:Synaptophysin; D012243:Rhodopsin
keywords: Atlantic cod; Ecotypes; Pan I; Polymorphism; Rhodopsin; Synaptic vesicle