uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Evolution of the insulin-like growth factor binding protein (IGFBP) family
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Dept of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Show others and affiliations
2011 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 152, no 6, 2278-2289 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2011. Vol. 152, no 6, 2278-2289 p.
Keyword [en]
IGFBP, IGF, growth regulation, genomics
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-129521DOI: 10.1210/en.2011-0047ISI: 000290788500015PubMedID: 21505050OAI: oai:DiVA.org:uu-129521DiVA: diva2:344172
Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2013-12-09Bibliographically approved
In thesis
1. Evolution of Vertebrate Endocrine and Neuronal Gene Families: Focus on Pituitary and Retina
Open this publication in new window or tab >>Evolution of Vertebrate Endocrine and Neuronal Gene Families: Focus on Pituitary and Retina
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 55 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 856
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, evolution, molekylär evolution, fylogeni
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-191829 (URN)978-91-554-8579-5 (ISBN)
Public defence
2013-03-01, B7:101a, Uppsala Biomedical Centre, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2013-02-07 Created: 2013-01-14 Last updated: 2013-04-02

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ocampo Daza, DanielSundström, GörelBergqvist, Christina ALarhammar, Dan
By organisation
PharmacologyDepartment of Neuroscience
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 221 hits
ReferencesLink to record
Permanent link

Direct link