4.3 Article

Conservation of sequence motifs suggests that the nonclassical MHC class I lineages CD1/PROCR and UT were established before the emergence of tetrapod species

期刊

IMMUNOGENETICS
卷 70, 期 7, 页码 459-476

出版社

SPRINGER
DOI: 10.1007/s00251-017-1050-2

关键词

MHC; Classical; Nonclassical; Phylogeny; Motifs

资金

  1. JSPS KAKENHI [22580213]
  2. Norwegian Veterinary Institute
  3. Grants-in-Aid for Scientific Research [22580213] Funding Source: KAKEN

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Humans have a number of nonclassical major histocompatibility complex (MHC) class I molecules that are quite divergent from the classical ones, and that may have separated from the classical lineage in pre-mammalian times. To estimate when in evolution the respective nonclassical lineages separated from the classical lineage, we first identified phylogenetic marker motifs within the evolution of classical MHC class I; the selected motifs are rather specific for and rather stably inherited within clades of species. Distribution of these motifs in nonclassical MHC class I molecules indicates that the lineage including the nonclassical MHC class I molecules CD1 and PROCR separated from the classical lineage before the emergence of tetrapod species, and that the human nonclassical MHC class I molecules FCGRT, MIC/ULBP/RAET, HFE, MR1, and ZAG show similarity with classical MHC class I at the avian/reptilian level. An MR1-like alpha 1 exon sequence was identified in turtle. Our system furthermore indicates that the lineage UT, hitherto only found in non-eutherian mammals, predates tetrapod existence, and we identified UT genes in reptiles. If only accepting wide distribution of a lineage among extant species as true evidence for ancientness, the oldest identified nonclassical MHC class I lineage remains the fish-specific lineage Z, which was corroborated in the present study by finding both Z and classical-type MHC class I sequences in a primitive fish, the bichir. In short, we gained important new insights into the evolution of classical MHC class I motifs and the probable time of origin of nonclassical MHC class I lineages.

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