GYPA, encoding glycophorin A (GPA), is associated with the MNS blood group system. GPA is the most abundant erythrocyte sialoglycoprotein, yet its primary function remains unclear. It serves as the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the malarial parasite Plasmodium falciparum, suggesting its importance in malaria-related selective pressures [1].

Observed patterns of variation in GYPA suggest it has been subject to balancing selection in malaria-endemic areas and in Europeans. Resequencing GYPA in individuals from malaria-endemic (sub-Saharan Africa and South India) and non-endemic (Europe and East Asia) regions showed evidence of balancing selection in malaria-endemic populations and Europeans, but not in East Asians, Oceanians, and Americans. This indicates that malaria may act as a selective pressure on GYPA, and another selective force may be at play in Europeans [1]. MNS blood group-related genes, including GYPA, have obvious polymorphism. Analysis of full-length mRNA sequences of GYPA from different phenotype-combined samples detected exon-6 deletion in one sample, while the other four had complete full-length GYPA mRNA, laying a foundation for studying GYPA gene structure and MNS blood group antigen expression [2].

In summary, GYPA is crucial in the context of the MNS blood group and malaria-related selective pressures. The discovery of its balancing selection in certain populations and its gene polymorphism enhance our understanding of its role in evolution and disease-related processes, especially in malaria-endemic regions [1,2].

References:

1. Bigham, Abigail W, Magnaye, Kevin, Dunn, Diane M, Weiss, Robert B, Bamshad, Michael. 2018. Complex signatures of natural selection at GYPA. In Human genetics, 137, 151-160. doi:10.1007/s00439-018-1866-3. https://pubmed.ncbi.nlm.nih.gov/29362874/

2. Liang, Yan-Lian, Wu, Fan, Liang, Shuang, Xu, Yun-Pin, Su, Yu-Qing. . [Polymorphism of the Full-Length mRNA Sequences of MNS blood group-related genes GYPA, GYPB and GYPE]. In Zhongguo shi yan xue ye xue za zhi, 31, 1537-1542. doi:10.19746/j.cnki.issn.1009-2137.2023.05.045. https://pubmed.ncbi.nlm.nih.gov/37846713/