Fig. 1.

Evolutionary history of the IL-1 receptor family. a Chromosomal gene location as evidence of ancestral relationship of IL-1 family members. The highly conserved nature of surrounding genes and sequence homology suggests two or one separate evolutionary families: IL-1R1, IL-1R2, IL-18R1, IL-1RL2, IL-1RL2 and IL-18RAP all form a cluster on the same chromosome, indicating gene duplication events. IL-1RAPL2 also has the MAP4K4 gene nearby indicating a duplication and translocation of that part of the chromosome. The ARX gene indicates that IL-1RAPL1 likely formed from a duplication of IL-1RAPL2. IL-1RAP shares no nearby genes but demonstrates high sequence identity with the IL-18RAP gene inferring homology. This suggests there is clear evidence that all the IL-1R superfamily genes have a common ancestor except for the SIGIRR gene, which has relatively low sequence identity and no chromosomal anatomy evidence to support shared ancestry. b Composite evolutionary history of the IL-1 family of cytokines constructed by overlaying the evidence from chromosomal location and clade IL-1 family gene profile on to the maximum likelihood tree from Supplementary Data 1. Dotted lines represent less established evidence of shared ancestry. The percentage of trees in which the associated group clustered together is shown next to the branches from 1000 bootstrap replications. Branches, which occur in <50% of trees were collapsed. The tree is drawn to scale, with branch lengths measured in the number of amino acid replacements per site. The analysis involved 231 amino acid sequences with an alignment length of 64 positions in the final data set. All positions containing gaps and missing data were eliminated. Scale bar is 0.5 replacements per site