Molecular Evolution of Glycophorins

Abstract

Humans and closely related apes have four glycophorin‐encoding genes, three of which form a small paralogous gene family. These genes encode sialoglycoproteins that localise to the plasma membrane of the red blood cell. Although the biological function of these proteins is not well understood, and their presence does not appear necessary for human viability or normal health, all four glycophorin‐encoding genes show evidence of accelerated evolution through positive natural selection. This selection is likely caused by a coevolutionary dynamic between glycophorins and Plasmodium falciparum receptors that use these molecules to gain entry into the red blood cell.

Key Concepts:

  • Gene duplication, followed by DNA sequence divergence and non‐homologous recombination, has shaped the GYPA‐GYPB‐GYPC gene family.

  • Positive natural selection, likely mediated by Plasmodium falciparum, has caused accelerated amino acid evolution at all glycophorin‐encoding genes.

Keywords: glycophorins; sialoglycoproteins; malaria; natural selection; gene duplication

Figure 1.

Two successive duplication events created the GYPAGYPBGYPE gene family in gorillas, chimpanzees and humans. GYPA represents the ancestral gene, which initially duplicated to form a precursor GYPB/E gene. Subsequently, this precursor duplicated to form GYPB and GYPE. Several additional structural changes have also affected these genes. A, The GYPB/E precursor gene acquired a novel 3′ sequence through nonhomologous recombination. This novel sequence replaced ancestral exons 6 and 7. B, In gorillas, GYPA contains two alleles that differ with respect to whether exon 3 is included in the final messenger ribonucleic acid (mRNA) transcript. C, In humans, ancestral exon 3 has been eliminated from the GYPB transcript. D, In all species, ancestral exon 3 has been eliminated from the final GYPE transcript. Ancestral exon 4 is also eliminated in humans and chimpanzees.

Figure 2.

Schematic representation of glycophorins C and D (GYPC and GYPD). The two proteins are encoded by separate in‐frame start codons from a single transcript. GYPC is encoded by the upstream start codon and has 63 amino acid residues on the exterior of the red blood cell (and a total of 128 amino acid residues in the entire protein). GYPD has 42 amino acids outside of the cell (and a total of 107 amino acid residues). The two proteins differ with respect to the extent of extracellular glycosylation (O‐linked glycans are indicated by red dots, N‐linked glycans in blue). Within the cell, the two proteins are identical, and both bind with protein 4.1.

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Further Reading

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Reid ME and Lomas‐Francis C (2004) The Blood Group Antigen Factsbook. Amsterdam, Boston: Elsevier/Academic Press.

Williams TN (2006) Red blood cell defects and malaria. Molecular and Biochemical Parasitology 149: 121–127.

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Wilder, Jason A(Sep 2010) Molecular Evolution of Glycophorins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022861]