The evolutionary history of Plasmodium falciparum from mitochondrial and apicoplast genomes of China-Myanmar border isolates

Abstract

Background: The frequent communication between African and Southeast Asian (SEA) countries has led to the risk of imported malaria cases in the China-Myanmar border (CMB) region. Therefore, tracing the origins of new malaria infections is important in the maintenance of malaria-free zones in this border region. A new genotyping tool based on a robust mitochondrial (mt) /apicoplast (apico) barcode was developed to estimate genetic diversity and infer the evolutionary history of Plasmodium falciparum across the major distribution ranges. However, the mt/apico genomes of P. falciparum isolates from the CMB region to date are poorly characterized, even though this region is highly endemic to P. falciparum malaria.

Methods: We have sequenced the whole mt/apico genome of 34 CMB field isolates and utilized a published data set of 147 mt/apico genome sequences to present global genetic diversity and to revisit the evolutionary history of the CMB P. falciparum.

Results: Genetic differentiation based on mt/apico genome of P. falciparum revealed that the CMB (Lazan, Myanmar) isolates presented high genetic diversity with several characteristics of ancestral populations and shared many of the genetic features with West Thailand (Mae Sot; WTH) and to some extent West African (Banjul, Gambia; Navrongo, Ghana; WAF) isolates. The reconstructed haplotype network displayed that the CMB and WTH P. falciparum isolates have the highest representation (five) in the five ancestral (central) haplotypes (H1, H2, H4, H7, and H8), which are comparatively older than isolates from other SEA populations as well as the WAF populations. In addition, the highest estimate of the time to the Most Recent Common Ancestor (TMRCA) of 42,400 (95% CI 18,300-82100) years ago was presented by the CMB P. falciparum compared to the other regional populations. The statistically significant negative values of Fu's Fs with unimodal distribution in pairwise mismatch distribution curves indicate past demographic expansions in CMB P. falciparum with slow population expansion between approximately 12,500-20,000 ybp.

Conclusions: The results on the complete mt/apico genome sequence analysis of the CMB P. falciparum indicated high genetic diversity with ancient population expansion and TMRCA, and it seems probable that P. falciparum might have existed in CMB, WTH, and WAF for a long time before being introduced into other Southeast Asian countries or regions. To reduce the impact of sample size or geographic bias on the estimate of the evolutionary timeline, future studies need to expand the range of sample collection and ensure the representativeness of samples across geographic distributions. Additionally, by mapping global patterns of mt/apico genome polymorphism, we will gain valuable insights into the evolutionary history of P. falciparum and optimised strategies for controlling P. falciparum malaria at international borders.

Keywords: Plasmodium falciparum; Apicoplast; China-Myanmar border; Evolutionary history; Mitochondrial.

Fig. 1

Reconstructed haplotype network of global Plasmodium falciparum isolates with whole mt/apico genome sequences. China-Myanmar border haplotypes are indicated by red color, West Africa by blue, West Cambodia by green, Vietnam by yellow, Laos by purple, and West Thailand by pink. The size of the circle is proportional to the haplotype frequency

Fig. 2

Mismatch distribution of pairwise number of differences at the China-Myanmar border for Plasmodium falciparum. The bars represent observed frequency of the pairwise differences among mt/apico genome sequences, and the line represents the expected curve for a population that has undergone a demographic expansion. Observed mismatch distribution was compared with that expected under the sudden demographic expansion model with a parametric bootstrap of 1000 replicates

Fig. 3

Bayesian skyline plot of China-Myanmar border Plasmodium falciparum showing changes in effective population size (Ne) through time. The Y-axis represents the effective population size on a logarithmic scale, and the X-axis represents time thousands of years ago. The thick solid blue line is the median estimate, and the blue shaded area represents the 95% highest probability density (HPD) intervals for effective population size