Genetic structure of two erythrocyte binding antigens of Plasmodium falciparum reveals a contrasting pattern of selection
| Autor: | Pramita Chowdhury, Srikanta Sen, Sanghamitra Sengupta, Sumana Datta Kanjilal |
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| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Microbiology (medical) Nonsynonymous substitution Protein Conformation In silico Plasmodium falciparum Population Protozoan Proteins Antigens Protozoan Biology Polymerase Chain Reaction Microbiology 03 medical and health sciences Genetic variation Genetics Antigenic variation Humans Glycophorin Glycophorins Malaria Falciparum Selection Genetic education Molecular Biology Gene Phylogeny Ecology Evolution Behavior and Systematics education.field_of_study 030102 biochemistry & molecular biology Genetic Variation Sequence Analysis DNA biology.organism_classification 030104 developmental biology Infectious Diseases biology.protein |
| Zdroj: | Infection, Genetics and Evolution. 57:64-74 |
| ISSN: | 1567-1348 |
| DOI: | 10.1016/j.meegid.2017.11.006 |
| Popis: | Erythrocyte binding antigens 175 (EBA-175) and 140 (EBA-140) play key roles in erythrocyte invasion by binding to glycophorin A (GPA) and C (GPC) respectively in human malaria. Since antigenic variation in malaria endemic region is a major barrier to development of effective vaccine, we explore the nature and pattern of sequence diversity of these two vaccine candidates in Kolkata, India. Population genetic parameters based on parasite sequences representing region II of Pfeba-175 and Pfeba-140 genes were estimated using DnaSP V.5.10 and MEGA version 6.0. A novel molecular docking approach was implemented to assess the binding affinities of Kolkata Pfeba-175 variants with GPA. P. falciparum Kolkata isolates experienced a recent population expansion as documented by negative Tajima's D, Fu & Li's statistics, unimodal mismatch distribution and star-like median-joining network for both loci. Positive selection seemed to play a major role in shaping the diversity of Pfeba-175 (dN/dS=2.45, and McDonald-Kreitman P-value=0.04) with successive accumulation of Q584K/E, E592A and R664S deriving high frequency haplotypes designated here as F2KH3 and F2KH1. In silico molecular docking demonstrated that polypeptides encoded by F2KH1 and F2KH3 were capable of engaging the parasite ligand into energetically favorable interaction with GPA. Our data demonstrated emergence of Pfeba-175 sequences harboring selectively advantageous nonsynonymous substitutions on Pf3D7 sequence background in the Kolkata parasite isolates. A contrasting pattern of Pf3D7-centric expansion of parasite sequences was noted for Pfeba-140. Together, this study provides a firm genetic and biological support favoring a dominant role of EBA-175 in erythrocyte invasion. |
| Databáze: | OpenAIRE |
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