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A Revised Timeline for the Origin of Plasmodium falciparum as a Human Pathogen

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Abstract

While Plasmodium falciparum is known to have had a strong effect on human evolution, the time period when P. falciparum first infected ancestors of modern humans has remained uncertain. Recent advances demonstrated that P. falciparum evolved from ancestors of gorilla parasites via host switching. Here, we estimate the range of dates during which this host switch may have occurred. DNA sequences of portions of the mitochondrial cytochrome b gene obtained from gorilla parasites closely related to human P. falciparum were aligned and compared against similar sequences from human P. falciparum. Time estimates were calculated by applying a previously established parasite cytochrome b gene mutation rate (0.012 mutations per site per million years) and by modeling uncertainty in a Monte–Carlo simulation. We estimate a 95% confidence interval for when P. falciparum first infected ancestors of modern humans to be 112,000 and 1,036,000 years ago (median estimate, 365,000 years ago). This confidence interval suggests that P. falciparum first infected human ancestors much more recently than the previous recognized estimate of 2.5 million years ago. The revised estimate may inform our understanding of certain aspects of human-malaria co-evolution. For example, this revised date suggests a closer relationship between the entry of P. falciparum in humans and the appearance of many red blood cell polymorphisms considered to be genetic adaptations to malaria. In addition, the confidence interval lies within the timeframe dating the dawn of Homo sapiens, suggesting that P. falciparum may have undergone host switching as a Plasmodia adaptation specific for our species.

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Acknowledgments

We would like to thank Dr. Christine Cserti-Gazdewich, Dr. Marcin Imielinski, and Dr. Daniel Neafsey for their thoughtful contributions to the manuscript.

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Authors and Affiliations

  1. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Room GRJ-235, 55 Fruit Street, Boston, MA, 02114, USA

    Jason M. Baron, John M. Higgins & Walter H. Dzik

  2. Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA

    John M. Higgins

  3. Department of Systems Biology, Harvard Medical School, Boston, MA, USA

    John M. Higgins

Authors
  1. Jason M. Baron
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  2. John M. Higgins
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  3. Walter H. Dzik
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Correspondence to Jason M. Baron.

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Baron, J.M., Higgins, J.M. & Dzik, W.H. A Revised Timeline for the Origin of Plasmodium falciparum as a Human Pathogen. J Mol Evol 73, 297–304 (2011). https://doi.org/10.1007/s00239-011-9476-x

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  • DOI: https://doi.org/10.1007/s00239-011-9476-x

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