Evidence for internal homology in bovine preproparathyroid hormone.

By means of a statistical method for detecting distant evolutionary relationships between proteins, we found a high probability that internal homologies exist in preproparathyroid hormone, the biological precursor of proparathyroid hormone and parathyroid hormone. The regions so defined were -27 to +22 of preproparathyroid hormone vs. +26 to +74 parathyroid hormone and -23 to +29 of preproparathyroid hormone vs. +30 to +81 of parathyroid hormone. Examination of these regions for possible similarities of internal secondary structure (beta turns, alpha helix, and beta sheet) by a second type of predictive formulation indicated that most of the regions calculated to be related on an evolutionary basis were likewise homologous in terms of structure. These results and other considerations suggest that a primitive form of parathyroid hormone, possibly of pituitary origin, existed (or still exists). Parathyroid hormone of higher species likely was formed by gene doubling and fusion of the primitive gene.