The genomics of Insulin 5

Advances in the development of sequence databases and novel bioinformatics algorithms have changed the way many new hormones are discovered. Nucleic acid sequence-based queries targeted to conserved features of the insulin/relaxin superfamily, have led to the discovery of a novel member of the relaxin family of hormones, INSL5 [1]. The discovery of a novel gene from DNA sequence permits the rapid analysis of gene expression patterns and chromosomal localization in an attempt to elucidate the normal physiological or pathological role of the hormone. However, the protein to gene discovery path practiced with all previously identified members of this hormone family benefited from the knowledge of the biologically active form of the hormone from the very onset, as well as a bioassay with which to follow the hormone. This is not the case with genomic discoveries since the signalling form of members of this hormone family are usually the product of multiple steps of posttranslational modification and for many members, the structure of the mature form is not obvious. In addition, the varied biological activities and unique organ and cellular location of the current members of the insulin/relaxin family make the elucidation of the biology of its orphan members a difficult task. The first steps toward our understanding of INSL5 biology has focused on experiments necessary to provide information on the structure of the mature hormone, the identification of some of the organ systems affected by its action, and the identification of a population of cells which make this hormone.