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Proc Natl Acad Sci U S A. 1990 Dec;87(23):9319-23.

Evolution of the insulin superfamily: cloning of a hybrid insulin/insulin-like growth factor cDNA from amphioxus.

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Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, University of Chicago, IL 60637.


Although insulin and the insulin-like growth factors (IGFs) share marked similarities in amino acid sequence and biological activity, their evolutionary origins have not been resolved. To investigate this issue, we recently cloned a cDNA encoding an insulin-like peptide (ILP) from a primitive chordate species, amphioxus (Branchiostoma californiensis). The deduced sequence of amphioxus preproILP indicates that it is a hybrid molecule containing features characteristic of both insulin and IGF. Like proinsulin, amphioxus proILP contains a C-peptide, which is flanked by paired basic residues and is probably removed by proteolysis. However, proILP also contains an extended carboxyl-terminal peptide region that can be divided into D and E domains similar to those of proIGF. Sequence comparisons show that the amphioxus ILP A and B domains are equally homologous to those of human insulin and IGF-I and -II. Based on these results and the exon-intron organization of the amphioxus ILP gene, we propose that IGF emerged at a very early stage in vertebrate evolution from an ancestral insulin-type gene.

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