Cloning of rabbit interleukin-1 beta: differential evolution of IL-1 alpha and IL-1 beta proteins

We have cloned the rabbit IL-1 beta cDNA, which encodes a 268 amino acid precursor similar in length to other sequenced IL-1 precursors. Comparison of all published IL-1 alpha and IL-1 beta sequences respectively indicates that the IL-1 alpha gene family is evolving faster than the IL-1 beta family, and that the two genes diverged approximately 270 million years ago. Surprisingly, there are differences in the regions preferentially conserved within the two families. The IL-1 alpha family is most conserved at the amino terminus whereas the IL-1 beta family is most conserved in the carboxy-terminal half. This is despite the fact that the carboxy-terminal half encodes the active portion of both molecules and would be expected to adopt a similar beta-sheet structure in IL-1 alpha as in the published X-ray structure of mature IL-1 beta. These findings suggest that differences in the function and properties of the IL-1 alpha and IL-1 beta precursor molecules may have been conserved. These differences may therefore provide an explanation for the existence of two IL-1 molecules.