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Unlike some other immune-system gene families, whose genes are all clustered together on one chromosome, the 10 human TLR genes are distributed between five chromosomes. This reflects the ancient, invertebrate origin of the Toll-like receptors, which were present before the two genome-wide duplications that occurred during the early evolution of the vertebrates around 500 million years ago. On the basis of sequence similarities, the Toll-like receptors form four evolutionary lineages (I, II, III, and IV) that are descendants of the four Toll-like receptor loci formed by these two ancient genome duplications.
