Mable BK et al. (2015), Copy number variation and genetic diversity of ...

XB-ART-51229

Immunogenetics 2015 Oct 01;6710:591-603. doi: 10.1007/s00251-015-0860-3.

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Copy number variation and genetic diversity of MHC Class IIb alleles in an alien population of Xenopus laevis.

Mable BK , Kilbride E , Viney ME , Tinsley RC .

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Xenopus laevis (the African clawed frog), which originated through hybridisation and whole genome duplication, has been used as a model for genetics and development for many years, but surprisingly little is known about immune gene variation in natural populations. The purpose of this study was to use an isolated population of X. laevis that was introduced to Wales, UK in the past 50 years to investigate how variation at the MHC compares to that at other loci, following a severe population bottleneck. Among 18 individuals, we found nine alleles based on exon 2 sequences of the Class IIb region (which includes the peptide binding region). Individuals carried from one to three of the loci identified from previous laboratory studies. Genetic variation was an order of magnitude higher at the MHC compared with three single-copy nuclear genes, but all loci showed high levels of heterozygosity and nucleotide diversity and there was not an excess of homozygosity or decrease in diversity over time that would suggest extensive inbreeding in the introduced population. Tajima's D was positive for all loci, which is consistent with a bottleneck. Moreover, comparison with published sequences identified the source of the introduced population as the Western Cape region of South Africa, where most commercial suppliers have obtained their stocks. These factors suggest that despite founding by potentially already inbred individuals, the alien population in Wales has maintained substantial genetic variation at both adaptively important and neutral genes.

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Species referenced: Xenopus laevis
Genes referenced: mhc2-dab myh6 rbm45 rel rtn3 tbx2

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Fig. 1. Comparison of MHC Class IIb sequences from Welsh X. laevis (XLA-HAP), published laboratory X. laevis (accession number indicated) and a domestic dog sequence from the DRB1 locus (DRB1*00101). Hypervariable regions (HVR; shaded) and antigen binding sites (ABS, asterisks) are as defined in Marsden et al. (2009) for canid haplotypes based on human HLA sequences described in Bondinas et al. (2007). Amino acid numbers start from the beginning of the exon 2 region sequenced for Welsh Xenopus. Bold indicates amino acids conserved among all Xenopus haplotypes and underlined are those also conserved across highly divergent canid species (domestic dogs and African Wild Dogs; taken from Marsden et al. 2009). In total, 21/64 amino acids were conserved among dogs and all Xenopus, with one occurring in an HVR but none at predicted ABS. Residues found to be under positive selection using the REL method, as implemented in datamonkey, are indicated by italics; the strongest selection was found at sites 3, 16 and 62, corresponding to one ABS in each of the HVR. Positive selection was detected at these sites for all other methods used as well (IFEL, FEL, MEME, SLAC). REL was the least conservative test, but sites 48 and 58 were also identified by most other methods; these are also at predicted ABS sites

Fig. 2. Mid-point rooted maximum likelihood genealogy for Class IIb sequences from Wales and published sequences, indicating the three putative loci described by Kobari et al. (1995); ‘type’ refers to the reference sequence for each locus reported in that paper. Bootstrap support (500 replicates) indicated when greater than 60 %. The Welsh sequences clearly cluster into DAB-like and DBB-like sequence types, but the remaining sequences do not resolve into a clearly distinctive grouping. For ease of comparison, they were designated as DCB. DAB-like genotypes segregated as expected for a single locus, but DCB (designated as Welsh haplotypes 5 and 8) and DBB were predominantly present as homozygotes. At least one sequence designated as DAB was present in all individuals sampled whereas DBB and DCB appeared to show presence/absence variation (PAV) among individuals (see Table 1)

References [+] :

Aguilar, High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. 2004, Pubmed