MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

Abstract

The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.

Keywords: Haplotyping; MHC; Next-generation sequencing; Non-human primates.

Fig. 1

Phylogenetic tree of Paan-A transcripts. The evolutionary history was inferred by using the maximum likelihood method based on the Jukes–Cantor model. Evolutionary analyses were conducted in MEGA7. The Paan-A*14 alleles are indicated by a blue background, and the alleles with a canonical Bw6 motif are indicated in blue, whereas Paan-A alleles with an identical Bw6 motif are shown in green

Fig. 2

Phylogenetic tree of Paan-B transcripts. The evolutionary history was inferred using the neighbour-joining method. The optimal tree with the sum of branch length = 1.85719168 is shown. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (1000 replicates) are shown next to the branches. Evolutionary analyses were conducted in MEGA7. The Paan-B*02 alleles are indicated by a blue background. Allele names are written without colon, e.g. Paan-B*0212 instead of the official allele designation Paan-B*02:12

Fig. 3

Paan-AB haplotypes defined by A-STR typing and NGS sequencing. B*02 alleles are given in bold. Possible crossing-over events between the A and B region or within the B region are illustrated by different colours. The D6S2859 lengths in brackets indicate that they are detected in most but not all animals within the respective haplotype; n.d. equals not detected; A? indicates that no A allele could be defined for this haplotype