Modelling and Construction of Pan-genome of Plasmodium Species: A Region Wise Analysis

Abstract

Malaria, a mosquito-borne disease, continues to be a global health problem due to antibiotic resistance and mutations by host and environmental factors. It is caused by a single cell protozoan known as Plasmodium, of which P. falciparum and P. vivax are the only prevalent causative agents in Pakistan. Since the genomes are prone to variation from region to region, a single representative isolate is not sufficient to describe the entire heterogeneity of a species across different geographical regions. Modelling the pan-genome could provide us with a better insight into how the parasites develop the genetic variability and determine the minimum set of essential genes and common virulence factors. This study aims to model three pan-genomes region-wise (strains taken globally, only from Asian countries, from Asian countries excluding Pakistan’s closest neighbour India. The Global pan-genome consisted of 2201 core genes (16.61%), 6716 accessory genes (70.7%) and 4329 unique genes (32.68%). The Asian pan-genome was comprised of 2587 core genes (23.06%), 4980 accessory genes (44.39%) and 3650 unique genes (32.53%). The Asian excluding India dataset was found out to be 2593 core genes (24.02%), 4719 accessory genes (43.72%) and 3480 genes (32.24%) as singletons. The study observed that when Pakistan’s closest neighbour India was included in the Asian dataset, it increased the singletons by 170 genes. The pan-genome is found to be open where the gene pool kept on increasing by an average of 150 genes being added on the subsequent addition of a new genome. However, the core genome decreased with the addition of new strains until it became stable. The stable core genome contains three orthologous clusters (OG1.5_2955, OG1.5_ 2969 and OG1.5_3338) directly listed as being involved in the pathogenesis (GO:0009405). They encode Parasitophorus Vacuolar Protein 1(PV1), Apical Membrane Protein 1 (AMA-1) and 6-cysteine protein P47, respectively. These core viral proteins need to be evaluated in future for potential drug and vaccine candidates that can help combat the disease irrespective of its origin or type.