Recent divergence from a common ancestor of human IFN-alpha genes.

Abstract

The two major classes of human type I interferons, leukocyte or α-interferon (IFN-α) and fibroblastor β-interferon (IFN-β) are antigenically distinct and encoded by separate structural genes1. Recently, genomic hybridization experiments have demonstrated the presence of ∼10 or more distinct human IFN-α (Hu IFN-α) genes which code for a family of homologous yet distinct proteins2,3, and 8 of these have been identified and sequenced3. In contrast, no evidence has been found for multiple Hu IFN-β genes3, although heterogeneity of Hu IFN-β mRNA has been observed4,5. The coding sequences of Hu IFN-α and IFN-β genes show weak but appreciable homology, indicating that they were derived from a common ancestor at a remote time6, whereas Hu IFN-α1 (a member of class D) and Hu IFN-α2 (a member of class A) diverged quite recently (∼22 Myr ago)7. We report here that all eight known IFN-α genes diverged from a common ancestor quite recently, at most ∼26 Myr ago. As mammalian divergence is known to have occurred ∼75 Myr ago8, this suggests that the IFN-α multigene family in primates is distinct in organization from that of other mammals. We provide evidence for a much lower rate of evolution for IFN-α G than for other α-interferons, and a rapid evolution of IFN-α E pseudogene similar to that of other pseudogenes9–11. A possible evolutionary origin of size heterogeneity in the 3′-noncoding region of IFN-α mRNAs is also discussed.