Abstract
Insulin has not only made major contributions to the field of clinical medicine but has also played central roles in the advancement of fundamental molecular biology, including evolution. Insulin is essential for the health of vertebrate species, yet its function has been modified in species-specific manners. With the advent of genome sequencing, large numbers of insulin coding sequences have been identified in genomes of diverse vertebrates and have revealed unexpected changes in the numbers of genes within genomes and in their sequence that likely impact biological function. The presence of multiple insulin genes within a genome potentially allows specialization of an insulin gene. Discovery of changes in proteolytic processing suggests that the typical two-chain hormone structure is not necessary for all of inulin’s biological activities.
Highlights
Insulin is well-characterized as a key regulator of blood glucose levels in vertebrates [1]
The discovery of insulin 100 years ago, led to a revolution in clinical medicine, as it allowed an effective treatment for diabetes [5]
In addition to its critical role in the history of clinical medicine, insulin has played key roles in the development of many revolutionary technologies that are commonplace in molecular biology, including protein sequencing [7] and the deduction of the three-dimensional structures of proteins [8]
Summary
Insulin is well-characterized as a key regulator of blood glucose levels in vertebrates [1]. While the relationships among these genes cannot be fully resolved by phylogenetic analysis, due to their short protein lengths, information derived from their locations within the genome has helped to largely resolve the order and timing of the gene duplication events that generated this gene family [18,19,20,21] As summarized, these studies suggest that the initial gene duplication event that originated this gene family separated an ancestor for the insulin and insulin-like growth factor (IGF1 and IGF2) genes from an ancestor of the insulin-like (INSL) and relaxin (RXN) genes. Insulin genes from diverse species representing multiple classes of vertebrates, including fish, frogs, and birds, have been characterized that share with the human gene a similar three exon (two coding) gene structure, and encode homologous protein sequences [30, 33]. In most vertebrates only a single insulin gene has been found, multiple copies of this gene, including some with differing gene structures, have been found in some species
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