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Evolution of Vertebrate Endocrine and Neuronal Gene Families: Focus on Pituitary and Retina
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The duplication of genes followed by selection is perhaps the most prominent way in which molecular biological systems gain multiplicity, diversity and functional complexity in evolution. Whole genome duplications (WGDs) therefore have the potential of generating an extraordinary amount of evolutionary innovation. It is now accepted that the vertebrate lineage has gone through two rounds of WGD in its early stages, after the divergence of invertebrate chordates and before the emergence of jawed vertebrates. These basal vertebrate WGDs are called 2R for two rounds of whole genome duplication. An additional WGD called 3R occurred early in the evolution of teleost fishes, before the radiation of this species-rich group. This thesis describes the evolution of several endocrine and neuronal gene families in relation to the vertebrate WGDs, through a comparative genomic approach including both phylogenetic analyses and chromosomal location data across a wide range of vertebrate taxa.

These results show that numerous endocrine gene families have expanded in 2R and in several cases also in 3R. These include the gene families of oxytocin and vasopressin receptors (OT/VP-R), somatostatin receptors (SSTR) and insulin-like growth factor binding proteins (IGFBP). For the OT/VP-R and SSTR families, previously undescribed subtypes were identified. The protein hormone family that includes growth hormone (GH), prolactin (PRL) and somatolactin (SL) acquired a new PRL gene in 2R, however the origins of GH, PRL and SL likely predate 2R. The corresponding family of receptors diversified during different time periods through a combination of local duplications and 3R.

Neuronal gene families of the visual system have also expanded in 2R and 3R. The results presented here demonstrate that the vertebrate repertoire of visual opsin genes arose in 2R as part of chromosomal blocks that also include the OT/VP-R genes. The gene families including the transducin alpha, beta and gamma subunits also arose in 2R, hinting at the importance of these events in the diversification and specialization of phototransduction cascades for rods and cones.

Thus, the whole genome duplications have been important contributors to the evolution of both vision and endocrine regulation in the vertebrates.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2013. , 55 s.
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 856
Nyckelord [en]
phylogenetics, evolution, molecular evolution, gene family evolution, genome duplication, gene duplication, oxytocin receptor, vasopressin receptor, visual opsin, transducin, growth hormone, prolactin, somatolactin, growth hormone receptor, prolactin receptor, somatostatin receptor, SSTR, IGFBP
Nyckelord [sv]
evolution, molekylär evolution, fylogeni
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-191829ISBN: 978-91-554-8579-5 (tryckt)OAI: oai:DiVA.org:uu-191829DiVA: diva2:587276
Disputation
2013-03-01, B7:101a, Uppsala Biomedical Centre, BMC, Husargatan 3, Uppsala, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2013-02-07 Skapad: 2013-01-14 Senast uppdaterad: 2013-04-02
Delarbeten
1. The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes
Öppna denna publikation i ny flik eller fönster >>The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes
2012 (Engelska)Ingår i: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 175, nr 1, 135-143 s.Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes.

Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-166957 (URN)10.1016/j.ygcen.2011.10.011 (DOI)000299065800016 ()22057000 (PubMedID)
Tillgänglig från: 2012-01-17 Skapad: 2012-01-17 Senast uppdaterad: 2013-02-14Bibliografiskt granskad
2. The vertebrate ancestral repertoire of five visual opsins was established in the two rounds of early vertebrate genome doublings
Öppna denna publikation i ny flik eller fönster >>The vertebrate ancestral repertoire of five visual opsins was established in the two rounds of early vertebrate genome doublings
Visa övriga...
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-191828 (URN)
Tillgänglig från: 2013-01-14 Skapad: 2013-01-14 Senast uppdaterad: 2013-02-14
3. Expansion of transducin subunit gene families in early vertebrate tetraploidizations
Öppna denna publikation i ny flik eller fönster >>Expansion of transducin subunit gene families in early vertebrate tetraploidizations
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2012 (Engelska)Ingår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 100, nr 4, 203-211 s.Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Hundreds of gene families expanded in the early vertebrate tetraploidizations including many gene families in the phototransduction cascade. We have investigated the evolution of the heterotrimeric G-proteins of photoreceptors, the transducins, in relation to these events using both phylogenetic analyses and synteny comparisons. Three alpha subunit genes were identified in amniotes and the coelacanth, GNAT1-3; two of these were identified in amphibians and teleost fish, GNAT1 and GNAT2. Most tetrapods have four beta genes, GNB1-4, and teleosts have additional duplicates. Finally, three gamma genes were identified in mammals, GNGT1, GNG11 and GNGT2. Of these, GNGT1 and GNGT2 were found in the other vertebrates. In frog and zebrafish additional duplicates of GNGT2 were identified. Our analyses show all three transducin families expanded during the early vertebrate tetraploidizations and the beta and gamma families gained additional copies in the teleost-specific genome duplication. This suggests that the tetraploidizations contributed to visual specialisations.

Nyckelord
G-protein, Gene duplication, Phototransduction, Teleost fish, Tetraploidization, Transducin
Nationell ämneskategori
Naturvetenskap
Identifikatorer
urn:nbn:se:uu:diva-181018 (URN)10.1016/j.ygeno.2012.07.005 (DOI)000308731600001 ()
Tillgänglig från: 2012-09-14 Skapad: 2012-09-14 Senast uppdaterad: 2015-03-11Bibliografiskt granskad
4. Evolution of the growth hormone (GH), prolactin (PRL) and somatolactin (SL) family
Öppna denna publikation i ny flik eller fönster >>Evolution of the growth hormone (GH), prolactin (PRL) and somatolactin (SL) family
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-191827 (URN)
Tillgänglig från: 2013-01-14 Skapad: 2013-01-14 Senast uppdaterad: 2013-02-14
5. The growth hormone receptor (GHR) and prolactin receptor (PRLR) gene family expanded in the basal teleost tetraploidization
Öppna denna publikation i ny flik eller fönster >>The growth hormone receptor (GHR) and prolactin receptor (PRLR) gene family expanded in the basal teleost tetraploidization
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-191826 (URN)
Tillgänglig från: 2013-01-14 Skapad: 2013-01-14 Senast uppdaterad: 2013-02-14
6. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements.
Öppna denna publikation i ny flik eller fönster >>The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements.
2012 (Engelska)Ingår i: BMC Evolutionary Biology, ISSN 1471-2148, Vol. 12, 231- s.Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Somatostatin and its related neuroendocrine peptides have a wide varietyof physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results: We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomalrearrangements. These events obscure the paralogy relationships but are still tractable thanks tothe many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions: Two ancestral SSTR-bearing chromosome regions were duplicated in the two basalvertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

Nyckelord
Somatostatin receptors, Whole genome duplications, Chromosome rearrangements
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-189967 (URN)10.1186/1471-2148-12-231 (DOI)000314219500001 ()
Tillgänglig från: 2013-01-05 Skapad: 2013-01-05 Senast uppdaterad: 2013-02-26Bibliografiskt granskad
7. Evolution of the insulin-like growth factor binding protein (IGFBP) family
Öppna denna publikation i ny flik eller fönster >>Evolution of the insulin-like growth factor binding protein (IGFBP) family
Visa övriga...
2011 (Engelska)Ingår i: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 152, nr 6, 2278-2289 s.Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The evolution of the insulin-like growth factor binding protein  (IGFBP) gene family has been difficult to resolve. The early discovery of IGFBP gene synteny with the HOX (homeobox) gene clusters suggested that IGFBP was quadrupled along with HOX in the ancestral vertebrate chromosome duplications. However, some recent articles have favored independent serial duplications of the IGFBP genes. By combining sequence-based phylogenies and chromosome information from multiple vertebrate species, we conclude that chromosome duplications did indeed expand the IGFBP repertoire. After the ancestral chordate IGFBP gene had undergone a local gene duplication, resulting in a gene pair adjacent to a HOX cluster, chromosome quadruplication of this pair took place in the two basal vertebrate tetraploidizations (2R). Subsequently one gene was lost from two of the four pairs, leading to six IGFBP genes in the fish-tetrapod ancestor. These six genes are presently found in placental mammals. In teleost fishes the situation is more complex: their third tetraploidization (3R) doubled the IGFBP repertoire from six to twelve members whereupon differential losses have occurred. The five sequenced teleost fish genomes retain 9-11 of IGFBP genes. This scenario is supported by the phylogenies of three adjacent gene families, namely the epidermal growth factor receptors (EGFR) and the Ikaros and distal-less (Dlx) transcription factors, in addition to the HOX clusters. The great ages for the IGFBP genes strongly suggest that they evolved distinct functions early in vertebrate evolution.

Nyckelord
IGFBP, IGF, growth regulation, genomics
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-129521 (URN)10.1210/en.2011-0047 (DOI)000290788500015 ()21505050 (PubMedID)
Tillgänglig från: 2010-08-18 Skapad: 2010-08-18 Senast uppdaterad: 2013-12-09Bibliografiskt granskad

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