Evolution of the interleukin-1 gene family in mammals

Abstract

The phylogeny of interleukin-1 family genes shows that human interleukin-1 alpha (IL-1 alpha) is more closely related to IL-1 alpha of the bovine than to IL-1 alpha of the mouse, whereas human interleukin-1 beta (IL-1 beta) is more closely related to IL-1 beta of the mouse than to IL-1 beta of the bovine. The IL-1 receptor antagonist (IL-1ra) shows homology to the C-terminal region of both IL-1 alpha and IL-1 beta. In the C-terminal region, the IL-1 alpha genes of human and mouse have diverged more from each other at nonsynonymous sites than have either IL-1 beta or IL-1ra; because the same pattern is not seen at synonymous sites, it must be due not to a difference in mutation rate but rather to a greater degree of functional constraint on this region in the IL-1 beta and IL-1ra proteins than in the IL-1 alpha protein. But synonymous sites in IL-1 beta of mouse have evolved more rapidly than in IL-1 beta of human, indicating a higher rate of mutation in the former gene. In the N-terminal region of the protein, nonsynonymous sites have evolved at similar rates in IL-1 alpha and IL-1 beta. The first exon of the IL-1ra gene, which encodes the leader peptide, shows evidence of homology with the first exon of IL-1 beta, which is not translated. Thus, it seems likely that IL-1ra evolved by duplication of an IL-1 beta gene and loss of expression of exons 2-4.

Interleukin-1 in fish

“…It has been estimated that IL-1ra diverged from IL-1 approximately 350 million years ago (Eisenberg et al, 1991), and thus could be absent in fish. It has also been suggested that the common ancestor of IL-1 and the IL-1ra may have undergone alternative splicing to produce the two di#erent molecules (Hughes, 1994). There is as yet no evidence of this in fish.…”

“…The IL-1ra has highest amino acid homology (26%) to IL-1 , and this together with homology between the signal peptide of IL-1ra and the first exon of IL-1 (which is not translated) suggests that IL-1ra evolved from a duplicated IL-1 gene that arose some 350 million years ago ( Fig. 1) (Hughes, 1994). Whilst IL-1ra binds to site A of the IL-1R in a similar manner to IL-1 and IL-1 , it makes a quite di#erent contact with domain 3 and does not interact with the proposed 'receptor trigger site' required for signal transduction (Schreuder et al, 1997).…”

MOLECULAR CLONING OF INTERLEUKIN 1β FROM RAINBOW TROUT ONCORHYNCHUS MYKISS REVEALS NO EVIDENCE OF AN ICE CUT SITE

“…36,37 Furthermore, estimates of when IL-1 and IL-1 diverged (285 million years ago) Identical (*) and similar (. or :) residues identified by the CLUSTAL programme are indicated.…”

From Gene to Organismal Phylogeny: Reconciled Trees and the Gene Tree/Species Tree Problem

“…This indicates that if the mammalian phylogeny used to construct Fig. 9 is correct then the IL-b genes are not orthologous (Hughes, 1994;p. 10).…”

“…The tree has a cost of 14 (4 duplications d 1 -d 4 and 10 losses) and was computed by reconciling the C-terminal region tree for IL-1 (Hughes, 1994;Fig. 2c) with the mammal tree ((((bovine,sheep),pig),human), rabbit,(mouse,rat)).…”