Skip to content

Research at St Andrews

Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes

Research output: Contribution to journalArticle


Open Access permissions



Whole genome duplication (WGD) was experienced twice by the vertebrate ancestor (2 rounds; 2R), again by the teleost fish ancestor (3R) and most recently in certain teleost lineages (4R). Consequently, vertebrate gene families are often expanded in 3R and 4R genomes. Arguably, many types of ‘functional divergence’ present across 2R gene families will exceed that between 3R/4R paralogues of genes comprising 2R families. Accordingly, 4R offers a form of replication of 2R. Examining if this concept has implications for molecular evolutionary research, we studied insulin-like growth factor (IGF) binding proteins (IGFBPs), whose six 2R family members carry IGF hormones and regulate interactions between IGFs and IGF1-receptors (IGF1Rs). Using phylogenomic approaches, we resolved the complete IGFBP repertoire of 4R-derived salmonid fishes (nineteen genes; thirteen more than human) and established evolutionary relationships/nomenclature with respect to WGDs. Traits central to IGFBP action were determined for all genes, including atomic interactions in IGFBP-IGF1/IGF2 complexes regulating IGF-IGF1R binding. Using statistical methods, we demonstrate that attributes of these protein interfaces are overwhelming a product of 2R IGFBP family membership, explain 49-68% of variation in IGFBP mRNA concentration in several different tissues and strongly predict the strength and direction of IGFBP transcriptional regulation under differing nutritional-states. The results support a model where vertebrate IGFBP family members evolved divergent structural attributes to provide distinct competition for IGFs with IGF1Rs, pre-disposing different functions in the regulation of IGF-signaling. Evolution of gene expression acted to ensure the appropriate physiological production of IGFBPs according to their structural specializations, leading to optimal IGF-signaling according to nutritional-status and the endocrine/local mode of action. This study demonstrates that relatively recent gene family expansion can facilitate inference of functional evolution within ancient genetic systems.


Original languageEnglish
Pages (from-to)1060-1076
JournalMolecular Biology and Evolution
Issue number5
Early online date29 Jan 2013
Publication statusPublished - May 2013

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Demonstration of the use of environmental DNA for the non-invasive genotyping of a bivalve mollusk, the European flat oyster (Ostrea edulis)

    Holman, L., Hollenbeck, C. M., Ashton, T. J. & Johnston, I. A., 19 Nov 2019, In : Frontiers in Genetics. 10, 7 p., 1159.

    Research output: Contribution to journalArticle

  2. Influence of feed ration size on somatic and muscle growth in landlocked dwarf and farmed Atlantic salmon Salmo salar

    Andersen, Ø., Vieira, V., Dessen, J-E. & Johnston, I. A., Apr 2019, In : Journal of Fish Biology. 94, 4, p. 614-620 7 p.

    Research output: Contribution to journalArticle

  3. Genomic tools and selective breeding in molluscs

    Hollenbeck, C. M. & Johnston, I. A., 18 Jul 2018, In : Frontiers in Genetics. 9, 15 p., 253.

    Research output: Contribution to journalReview article

  4. A collaborative European approach to accelerating translational marine science

    Brennecke, P., Ferrante, M., Johnston, I. A. & Smith, D., 5 Jul 2018, In : Journal of Marine Science and Engineering. 6, 3, 12 p., 81.

    Research output: Contribution to journalArticle

Related by journal

  1. Molecular Biology and Evolution (Journal)

    Carolin Kosiol (Member of editorial board)
    2018 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. Purifying selection in corvids is less efficient on islands

    Kutschera, V. E., Poelstra, J. W., Botero-Castro, F., Dussex, N., Gemmell, N. J., Hunt, G. R., Ritchie, M. G., Rutz, C., Wiberg, R. A. W. & Wolf, J. B. W., Feb 2020, In : Molecular Biology and Evolution. 37, 2, p. 469-474 6 p.

    Research output: Contribution to journalArticle

  2. Polymorphism-aware species trees with advanced mutation models, bootstrap and rate heterogeneity

    Schrempf, D., Minh, B. Q., von Haeseler, A. & Kosiol, C., Jun 2019, In : Molecular Biology and Evolution. 36, 6, p. 1294-1301 8 p.

    Research output: Contribution to journalArticle

  3. Horizontal Gene Transfer from Bacteria Has Enabled the Plant-Parasitic Nematode Globodera pallida to Feed on Host-Derived Sucrose

    Danchin, E. G. J., Guzeeva, E. A., Mantelin, S., Berepiki, A. & Jones, J. T., 2 Jun 2016, In : Molecular Biology and Evolution. 33, 6, p. 1571-1579 9 p.

    Research output: Contribution to journalArticle

  4. Genome-wide DNA methylation patterns in wild samples of two morphotypes of threespine stickleback (Gasterosteus aculeatus)

    Smith, G., Smith, C., Kenny, J., Chaudhuri, R. & Ritchie, M. G., Apr 2015, In : Molecular Biology and Evolution. 32, 4, p. 888-895

    Research output: Contribution to journalArticle

  5. Multiple Cross-Species Transmission Events of Human Adenoviruses (HAdV) during Hominine Evolution

    Hoppe, E., Pauly, M., Gillespie, T. R., Akoua-Koffi, C., Hohmann, G., Fruth, B., Karhemere, S., Madinda, N. F., Mugisha, L., Muyembe, J-J., Todd, A., Petrzelkova, K. J., Gray, M., Robbins, M., Bergl, R. A., Wittig, R. M., Zuberbühler, K., Boesch, C., Schubert, G., Leendertz, F. H. & 2 others, Ehlers, B. & Calvignac-Spencer, S., Aug 2015, In : Molecular Biology and Evolution. 32, 8, p. 2072-84 13 p.

    Research output: Contribution to journalArticle

ID: 45159464