Cloning of rabbit interleukin-1β: differential evolution of IL-1α and IL-1β proteins

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