Human chromosome 5
Human chromosome 5

One of the genes I’m interested in is an aminopeptidase called “ERAP1″1 that’s involved in antigen presentation.2 ERAP1 is a member of a family of closely-related genes, roughly 50% identity, that in humans and many other mammals are adjacent on a chromosome. That is, on human chromosome 5 (figure to the right), there are three genes side by side: ERAP1; ERAP2; and LNPEP, all of which are clearly the result of gene-duplication events at some point. Several other mammals have the same arrangement. The neighbouring (non-ERAP-related) genes are the same, also, for that matter.

In mice and rats, however, there’s a different arrangement. ERAP1 is on chromosome 13, LNPEP is on chromosome 17, and there’s no ERAP2.

So it seemed that the most likely scenario was the in the rodent lineage, there was a chromosome break right between ERAP1 and LNPEP, right in the middle of ERAP2, that destroyed ERAP2. However, it was also possible (though I thought less likely) that there was a fusion — that having ERAP1 and LNPEP on different chromosomes was the basal situation, but that the chromosomes merged in the non-rodent lineage, with a gene duplication arising from the chromosome fusion. Or something like that.

Fish have members of the ERAP family, but I wasn’t confident in assigning them to ERAP1, ERAP2, or LNPEP — the mammalian genes are too similar for me to be confident in my feeble bioinformatic understanding.

Playpus ERAPs

But the platypus genome that just come out gives a lot of support to the idea that rodents split their chromosome from the basal patterns. To the left (click for a larger version) is the appropriate platypus chromosome. ERAP1 (here called “similar to type I tumor necrossis factor receptor shedding aminopeptidase regulator”) and LNPEP (here called “similar to leucyl/cystinyl aminopeptidase”) are on the same chromosome, and in between them is “LOC10081647″ — something the annotation called a pseudogene, which it may well be, but it’s ERAP2. I haven’t had time to do any careful alignments, but it aligns more closely with mammalian ERAP2 than anything else.

So almost certainly mice and rats lost ERAP2, though it may have been a pseudogene at that point, and other species either kept a functional ERAP2, or somewhere along the line turned a pseudogene into a functional enzyme.

This is not a big deal and likely won’t lead anywhere, but it’s an answer to a piece of trivia that’s been bothering me a little on and off for about 5 years. So yay for the platypus genome.

  1. by us, anyway: York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, Rock KL (2002) The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol 3:1177–184. [↩]
  2. For example, York IA, Brehm MA, Zendzian S, Towne CF, Rock KL (2006) Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance. Proc Natl Acad Sci U S A 103:9202–9207.[↩]