Human Genetics

, Volume 137, Issue 2, pp 151–160 | Cite as

Complex signatures of natural selection at GYPA

  • Abigail W. Bigham
  • Kevin Magnaye
  • Diane M. Dunn
  • Robert B. Weiss
  • Michael Bamshad
Original Investigation

Abstract

The human MN blood group antigens are isoforms of glycophorin A (GPA) encoded by the gene, GYPA, and are the most abundant erythrocyte sialoglycoproteins. The distribution of MN antigens has been widely studied in human populations yet the evolutionary and/or demographic factors affecting population variation remain elusive. While the primary function of GPA is yet to be discovered, it serves as the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the malarial parasite, Plasmodium falciparum, a major selective pressure in recent human history. More specifically, exon two of GYPA encodes the receptor-binding ligand to which P. falciparum binds. Accordingly, there has been keen interest in understanding what impact, if any, natural selection has had on the distribution of variation in GYPA and exon two in particular. To this end, we resequenced GYPA in individuals sampled from both P. falciparum endemic (sub-Saharan Africa and South India) and non-endemic (Europe and East Asia) regions of the world. Observed patterns of variation suggest that GYPA has been subject to balancing selection in populations living in malaria endemic areas and in Europeans, but no such evidence was found in samples from East Asia, Oceania, and the Americas. These results are consistent with malaria acting as a selective pressure on GYPA, but also suggest that another selective force has resulted in a similar pattern of variation in Europeans. Accordingly, GYPA has perhaps a more complex evolutionary history, wherein on a global scale, spatially varying selective pressures have governed its natural history.

Notes

Acknowledgements

AWB was supported by a training fellowship from the NIH–National Human Genome Research Institute (T32HG00035). The authors thank Anita Beck, Kati Buckingham, and Heidi Gildersleeve for thoughtful discussions on the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

439_2018_1866_MOESM1_ESM.docx (67 kb)
Supplementary material 1 (DOCX 66 kb)
439_2018_1866_MOESM2_ESM.xlsx (112 kb)
Supplementary material 2 (XLSX 112 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of AnthropologyThe University of MichiganAnn ArborUSA
  2. 2.Department of Human GeneticsThe University of ChicagoChicagoUSA
  3. 3.Department of Human GeneticsThe University of UtahSalt Lake CityUSA
  4. 4.Departments of Pediatrics and Genome SciencesThe University of WashingtonSeattleUSA

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