TY - JOUR
T1 - Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes
AU - MacQueen, Daniel John
AU - Garcia de la Serrana Castillo, Daniel
AU - Johnston, Ian Alistair
N1 - This work was supported by the Marine Alliance for Science and Technology for Scotland pooling initiative, funded by the Scottish Funding Council (grant number HR09011) and contributing institutions.
PY - 2013/5
Y1 - 2013/5
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.
U2 - 10.1093/molbev/mst017
DO - 10.1093/molbev/mst017
M3 - Article
SN - 0737-4038
VL - 30
SP - 1060
EP - 1076
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
IS - 5
ER -