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

Daniel J Macqueen, Daniel Garcia de la Serrana, Ian A Johnston

Research output: Contribution to journalArticle

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Abstract

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
Number of pages17
JournalMolecular Biology and Evolution
Volume30
Issue number5
Early online date29 Jan 2013
DOIs
Publication statusPublished - 2013

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Insulin-Like Growth Factor Binding Proteins
insulin-like growth factor binding proteins
somatomedins
salmonid
Somatomedins
Vertebrates
Fishes
vertebrate
genome
vertebrates
Genome
protein
fish
gene
Genes
genes
receptors
teleost
nutritional status
ancestry

Keywords

  • evolutionary genomics
  • functional evolution
  • gene family expansion
  • genome duplication
  • insulin-like growth factor system
  • insulin-like growth factor binding proteins

Cite this

Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes. / Macqueen, Daniel J; de la Serrana, Daniel Garcia; Johnston, Ian A.

In: Molecular Biology and Evolution, Vol. 30, No. 5, 2013, p. 1060-1076.

Research output: Contribution to journalArticle

Macqueen, Daniel J ; de la Serrana, Daniel Garcia ; Johnston, Ian A. / Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes. In: Molecular Biology and Evolution. 2013 ; Vol. 30, No. 5. pp. 1060-1076.
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N2 - 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.

AB - 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.

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