A New Method for Estimating Species Age Supports the Coexistence of Malaria Parasites and Their Mammalian Hosts

Abstract

Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including the speciation event that led to the subgenera Drosophila and Sophophora, and age of the melanogaster species subgroup. We applied this approach to hundreds of loci from seven mammalian Plasmodium species. We demonstrate the existence of a molecular clock specific to individual Plasmodium proteins, and estimate the relative age of mammalian-infecting Plasmodium. These analyses indicate that: 1) the split between the human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred 6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites originated 22 times earlier than the split between P. falciparum and P. reichenowi. Calibrating the absolute divergence times for Plasmodium with eukaryotic substitution rates, we show that the split between P. falciparum and P. reichenowi occurred 3.0–5.5 Ma, and that mammalian Plasmodium parasites originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium evolved contemporaneously with their hosts, with little evidence for parasite host-switching on an evolutionary scale, and provide a solid timeframe within which to place the evolution of new Plasmodium species.

Diversification by host switching and dispersal shaped the diversity and distribution of avian malaria parasites in Amazonia

“…Our estimates of the timing of cladogenic events differ from previous studies (Bensch et al 2013, Silva et al 2015. The greatest conflict was with Silva et al (2015), who estimated an older time of origin and radiation of mammalian Plasmodium compared to Ricklefs and Outlaw (2010).…”

“…Our estimates of the timing of cladogenic events differ from previous studies (Bensch et al 2013, Silva et al 2015. The greatest conflict was with Silva et al (2015), who estimated an older time of origin and radiation of mammalian Plasmodium compared to Ricklefs and Outlaw (2010). To assess the effect of using different published clock rates, we ran an alternative BEAST dating scheme using the most recent molecular clock substitution rate published by Pacheco et al (2018) and compared that to our analysis using the substitution rate published by Ricklefs and Outlaw (2010).…”

Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution

“…Regarding the estimation of divergence times using genomic information, different methods were recently used for Plasmodium, such as the one implemented in G-PhoCS 28 or the one developed by Silva et al 29 . G-PhoCS uses a Bayesian MCMC approach to infer, based on the information provided by multiple loci, the divergence time between species.…”

“…This method has been applied in two recent studies for Plasmodium parasites: one aiming at estimating the relative split times between the two P. ovale sub-species and between P. malariae and P. malariae-like 14 ; the other to estimate the divergence time within the Laverania subgenus, a subgenus including P. falciparum and all its closest aperelatives 13 . The Silva method is based on the estimate of the sequence divergence in different proteins and comparison of this divergence measured between different lineages 29 . In this method, the regression slope of the divergence between the proteins in two lineages reflects their relative age.…”

“…P. vivax-like samples were identified either by amplifying and sequencing the Plasmodium Cytochrome b (Cytb) gene as described in Ollomo et al or directly from samples already studied for other Plasmodium species 29,38 . This allowed the detection of 11 P. vivax-like samples, 10 from chimpanzees and 1 from an Anopheles moucheti mosquito.…”