Biomaterial Database

Coevolution of insulin-like growth factors, insulin and their receptors and binding proteins in New World Monkeys. 2015

Michael Wallis

Biochemistry and Biomedicine Group, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK. Electronic address: M.Wallis@sussex.ac.uk.

Previous work has shown that the evolution of both insulin-like growth factor 1 (IGF1) and insulin shows an episode of accelerated change on the branch leading to New World Monkeys (NWM). Here the possibility that this is accompanied by a corresponding episode of accelerated evolution of IGF1 receptor (IGF1R), insulin receptor (IR) and/or IGF binding proteins (IGFBPs) was investigated. Analysis of receptor sequences from a range of primates and some non-primate mammals showed that accelerated evolution did indeed occur on this branch in the case of IGF1R and IR, but not for the similar insulin receptor-related receptor (IRRR) which does not bind insulin or IGF1. Marked accelerated evolution on this branch was also seen for some IGFBPs, but not the mannose 6-phosphate/IGF2 receptor or epidermal growth factor receptor. The rate of evolution slowed before divergence of the lineages leading to the NWM for which sequences are available (Callithrix and Saimiri). For the IGF1R and IR, the accelerated evolution was most marked for the extracellular domains (ectodomains). Application of the branch-site method showed dN/dS ratios significantly greater than 1.0 for both receptor ectodomains and for IGFBP1, and allowed identification of residues likely to have been subject to selection. These residues were concentrated in the N-terminal half of the IGF1R ectodomain but the C-terminal half of the IR ectodomain, which could have implications for the formation of hybrid receptors. Overall the results suggest that adaptive coevolution of IGF1, insulin and their receptors and some IGFBPs occurred during the evolution of NWM. For the most part, the residues that change on this branch could not be associated with specific functional aspects (ligand binding, receptor dimerization, glycosylation) and the physiological significance of this coevolution remains to be established.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D002144	Callithrix	A genus of the subfamily CALLITRICHINAE occurring in forests of Brazil and Bolivia and containing seventeen species.	Callithrix jacchus,Hapale,Marmoset, Common,Marmoset, Short-Tusked,Marmosets,Common Marmoset,Common Marmosets,Marmoset,Marmoset, Short Tusked,Short-Tusked Marmoset,Short-Tusked Marmosets
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012453	Saimiri	A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.	Monkey, Squirrel,Squirrel Monkey,Monkeys, Squirrel,Saimirus,Squirrel Monkeys
D013002	Somatomedins	Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism.	Sulfation Factor,Somatomedin,Factor, Sulfation
D017451	Receptors, Somatomedin	Cell surface receptors that bind somatomedins and trigger intracellular changes which influence the behavior of cells. Studies have disclosed two types of receptors for this family of peptide hormones. The type I receptor is homologous to the insulin receptor and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor which is important in trafficking of lysosomal enzymes.	Receptors, Insulin-Like Growth Factors,Somatomedin Receptors,Insulin-Like Growth Factor Receptor,Insulin-Like Growth Factor Receptors,Somatomedin Receptor,Insulin Like Growth Factor Receptor,Insulin Like Growth Factor Receptors,Receptor, Somatomedin,Receptors, Insulin Like Growth Factors
D051078	Platyrrhini	An infraorder of New World monkeys, comprised of the families AOTIDAE; ATELIDAE; CEBIDAE; and PITHECIIDAE. They are found exclusively in the Americas.	Monkeys, New World,Monkey, New World,New World Monkey,New World Monkeys,World Monkey, New,World Monkeys, New
D018969	Insulin-Like Growth Factor Binding Proteins	A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)	IGF Binding Protein,IGF-Binding Protein,IGF-Binding Proteins,IGFBP,Insulin-Like Growth Factor Binding Protein,Somatomedin-Binding Protein,Somatomedin-Binding Proteins,Binding Protein, IGF,IGF Binding Proteins,Insulin Like Growth Factor Binding Protein,Protein, IGF Binding,Protein, IGF-Binding,Protein, Somatomedin-Binding,Somatomedin Binding Protein,Somatomedin Binding Proteins
D019143	Evolution, Molecular	The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.	Molecular Evolution,Genetic Evolution,Evolution, Genetic