Evolutionary genetics of malaria parasites
Plasmodium, the causative agent of malaria, is one of the most interesting parasites that impacts human health worldwide. It is a parasite with a complex life cycle, that involves sexual reproduction in the mosquito (vector), and asexual stages in different tissues of its vertebrate host. It infects many different vertebrate hosts, including several species of non-human primates, and most of the evidence suggests that the four Plasmodium species infecting humans, might have resulted from a host shift from a non-human parasite. We are interested in improving our understanding of the evolutionary history of Plasmodium vivax, and develop new approaches for understanding the evolution of its genomic architecture and the generation of antigenic variation. Some of our recent work has led us to show how the effective population size (Ne) of Plasmodium vivax changes along the chromosomes with a clear increase towards sub-telomeric regions. We are still working on additional analyses to better understand the implications of this pattern on the evolution of genomic architecture in P. vivax.
Our previous work (see publications) suggests that Plasmodium vivax is more closely related to parasites infecting macaques than it is to parasite species infecting african primates. This work was followed by a more thorough analysis where we estimated the time to most recent common ancestor (TMRCA) of Plasmodium vivax populations, using full mitochondrial genomes, under the coalescent that revealed Asian populations being the oldest populations of this particular species of Plasmodium.
Our interest in understanding the demographic history of Plasmodium vivax is not only an academic exercise, but also a necessary step towards understanding the ecological scenario in which selection has acted, how adaptation to the human host has historically occurred, and how drug resistance rises and spread in the population. Because recombination is tied to transmission, understanding the dynamics of seasonal epidemics and the overall historical changes will eventually help us make predictions about the speed at which adaptive evolution can occur in this species.
In my laboratory, we are currently developing protocols for DNA enrichment and whole genome sequencing of Plasmodium parasites to expand on previous work we have done to understand the demographic history of the parasite and identify signatures of selection in this organism.
Cornejo OE, Fisher D, Escalante AA. (2015) Genome-wide patterns of genetic polymorphism and signatures of selection in Plasmodium vivax. Genome Biology and Evolution 7(1): 106-119. (Highlighted in Nature Reviews Microbiology in the News and Analysis – Genome Watchsection, March 2015)
Pacheco MA, Battistuzzi FU, Junge RE, Cornejo OE, Williams CV, Landau I, Rabetafika L, Snounou G, Jones-Engel L, Escalante AA. (2011) Timing the origin of human malarial: the lemur puzzle. BMC Evolutionary Biology. doi: 10.1186/1471-2148-11-299.
Krief S, Escalante AA, Pacheco MA, Mugisha L, André C, Halbwax M, Fischer A, Krief JM, Kasenene JM, Crandfield M, Cornejo OE, Chavatte JM, Lin C, Letourneur F, Grüner AC, McCutchan TF, Rénia L, Snounou G. On the diversity of malaria parasites in African Apes and the origin of Plasmodium falciparum from Bonobos. PLoS Pathogens 6(2): e1000765. doi:10.1371/journal.ppat.1000765.
Cornejo OE, Escalante AA. (2006) The origin and age of Plasmodium vivax. Trends in Parasitology, 22(12): 558-563.
Escalante AA, Cornejo OE, Freeland DE, Poe AC, Durrego E, Collins WE, Lal AA. (2005) A monkey’s tale: The origin of Plasmodium vivax as a human malaria parasite. Proceedings of the National Academy of Sciences (USA) 102(6).
Escalante AA, Cornejo OE, Rojas A, Udhayakumar V, Lal AA. (2004) Assessing the effect of natural selection in malaria parasites. Trends in Parasitology, 20(8): 388-395.