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Published online on March 31, 2006, 10.1073/pnas.0600643103
PNAS | April 11, 2006 | vol. 103 | no. 15 | 5864-5868
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BIOLOGICAL SCIENCES / EVOLUTION
Reactivation by exon shuffling of a conserved HLA-DR3-like pseudogene segment in a New World primate species

Gaby G. M. Doxiadis{dagger},{ddagger}, Marit K. H. van der Wiel{dagger}, Herbert P. M. Brok§, Natasja G. de Groot{dagger}, Nel Otting{dagger}, Bert A. ’t Hart, Jon J. van Rood||,{dagger}{dagger}, and Ronald E. Bontrop{dagger}

Departments of {dagger}Comparative Genetics and Refinement, §Animal Science, and Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands; and ||Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, E3-Q, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

Contributed by Jon J. van Rood, February 1, 2006

The common marmoset (Callithrix jacchus), a New World monkey species with a limited MHC class II repertoire, is highly susceptible to certain bacterial infections. Genomic analysis of exon 2 sequences documented the existence of only one DRB region configuration harboring three loci. Two of these loci display moderate levels of allelic polymorphism, whereas the -DRB*W12 gene appears to be monomorphic. This study shows that only the Caja-DRB*W16 and -DRB*W12 loci produce functional transcripts. The Caja-DRB1*03 locus is occupied by a pseudogene, given that most of the transcripts, if detected at all, show imperfections and are present at low levels. Moreover, two hybrid transcripts were identified that feature the evolutionarily conserved peptide-binding motif characteristic for the Caja-DRB1*03 gene. Thus, the severely reduced MHC class II repertoire in common marmosets has been expanded by reactivation of a pseudogene segment as a result of exon shuffling.

MHC | non-human primates | selection | immune response | evolution

Freely available online through the PNAS open access option.

Author contributions: G.G.M.D., B.A.t.H., J.J.v.R., and R.E.B. designed research; M.K.H.v.d.W., H.P.M.B., and N.O. performed research; H.P.M.B. and B.A.t.H. contributed new reagents/analytic tools; G.G.M.D., M.K.H.v.d.W., and N.G.d.G. analyzed data; and G.G.M.D. and R.E.B. wrote the paper.

Conflict of interest statement: No conflicts declared.

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AM114038–AM114059 and AM180875).

{ddagger}To whom correspondence may be addressed at: Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ, Rijswijk, The Netherlands. E-mail: doxiadis{at}bprc.nl

{dagger}{dagger}To whom correspondence may be addressed. E-mail: vanrood{at}europdonor.nl

© 2006 by The National Academy of Sciences of the USA


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