Mitochondrial population genomic analyses reveal population structure and demography of Indian Plasmodium falciparum

Inference on the genetic diversity of Plasmodium falciparum populations could help in better management of malaria. A very recent study with mitochondrial (mt) genomes in global P. falciparum had revealed interesting evolutionary genetic patterns of Indian isolates in comparison to global ones. However, no population genetic study using the whole mt genome sequences of P. falciparum isolates collected in the entire distribution range in India has yet been performed. We herewith have analyzed 85 whole mt genomes (48 already published and 37 entirely new) sampled from eight differentially endemic Indian locations to estimate genetic diversity and infer population structure and historical demography of Indian P. falciparum. We found 19 novel Indian-specific Single Nucleotide Polymorphisms (SNPs) and 22 novel haplotypes segregating in Indian P. falciparum. Accordingly, high haplotype and nucleotide diversities were detected in Indian P. falciparum in comparison to many other global isolates. Indian P. falciparum populations were found to be moderately sub-structured with four different genetic clusters. Interestingly, group of local populations aggregate to form each cluster; while samples from Jharkhand and Odisha formed a single cluster, P. falciparum isolates from Asom formed an independent one. Similarly, Surat, Bilaspur and Betul formed a single cluster and Goa and Mangalore formed another. Interestingly, P. falciparum isolates from the two later populations were significantly genetically differentiated from isolates collected in other six Indian locations. Signature of historical population expansion was evident in five population samples, and the onset of expansion event was found to be very similar to African P. falciparum. In agreement with the previous finding, the estimated Time to Most Recent Common Ancestor (TMRCA) and the effective population size were high in Indian P. falciparum. All these genetic features of Indian P. falciparum with high mt genome diversity are somehow similar to Africa, but quite different from other Asian population samples.