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Biological implication for loss of function at major histocompatibility complex loci

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Abstract

Despite relatively frequent gene or segment duplications, the number of functional loci in the major histocompatibility complex (MHC) is relatively small. The dual function of MHC molecules (triggering the immune system and limiting T-cell receptor repertoires) is likely to balance the number of functional loci. The effect of this dual function on the number of functional MHC loci has been argued mainly in the theoretical and computer simulation studies, but the evidence from empirical data has not been fully examined. Here, we attempt to evaluate this effect based on the analysis of nucleotide sequence data. We hypothesized that due to the dual function, even becoming a pseudogene (pseudogenization) of MHC is advantageous for the organisms. To evaluate this hypothesis, we compared the distribution of the waiting time (T W) till pseudogenization for HLA (human MHC) with that of the human olfactory receptor (OR) and bitter taste receptor (T2R) genes. The result shows that T W in HLA has a tendency to be relatively shorter as the emergence time (T) of the gene becomes older, while in OR T W becomes proportionally longer as T becomes older and in T2R it is almost null irrespective of T. Furthermore, T W in HLA is strongly influenced by the extent of functional differentiation in the peptide-binding region. Taken together, these results show that MHC molecules have optimal numbers of functional loci, and these numbers are regulated by the advantageous pseudogenization of duplicated copies.

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Acknowledgments

We thank Dr. Naoyuki Takahata and an anonymous reviewer for helpful comments to the earlier version of this manuscript. This research was supported in part by the Grant-in-Aid for Scientific Research (S) 16107001 from the Japanese Society for the Promotion of Science (JSPS).

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Correspondence to Yoko Satta.

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Supplementary Information 1

Olfactory receptors (OR) (PDF 46.9 KB)

Supplementary Information 2

Bitter taste receptors (T2R) (PDF 27.7 KB)

Supplementary Information 3

Alleles used in the present analysis (PDF 22.4 KB)

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Sawai, H., Go, Y. & Satta, Y. Biological implication for loss of function at major histocompatibility complex loci. Immunogenetics 60, 295–302 (2008). https://doi.org/10.1007/s00251-008-0291-5

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