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Evolution of a malaria resistance gene in wild primates

Nature volume 460, pages 388–391 (2009)Cite this article

Abstract

The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax1,2,3. We identified variation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons4,5. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans6,7,8. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.

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Figure 1: Schematic of the baboon FY gene (not to scale).
Figure 2: Genotype at the FY cis -regulatory A/G SNP is associated with Hepatocystis infection.
Figure 3: Allelic imbalance is associated with FY cis -regulatory genotype.
Figure 4: FY cis -regulatory variation drives differential expression in vitro.

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Accession codes

Data deposits

Sequence data have been deposited in NCBI GenBank under the accession numbers FJ952954–FJ955880, FJ955882–FJ955885, FJ955887–FJ955896 and FJ955899–FJ956699.

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Acknowledgements

We thank the Office of the President of the Republic of Kenya and the Kenya Wildlife Service for permission to work in Amboseli National Park, and the Institute of Primate Research for local sponsorship. We thank the wardens and staff of Amboseli National Park, and the pastoral communities of Amboseli and Longido for cooperation. We thank J. Altmann for providing access to long-term data and contributing samples, and J. Altmann and Y. Gilad for providing comments on the manuscript. R. S. Mututua, S. Sayialel, and J. K. Warutere assisted with sample collection. The Integrated Primate Biomaterials and Information Resource, the Coriell Institute, J. Rogers and R. Sapolsky provided access to DNA samples from Mikumi and Masai Mara respectively. G. Gibson, T. F. C. Mackay, L. Goering and D. Tan provided access to a pyrosequencer at NC State University. M. Akinyi assisted with sample collection and analysis. A. D. Pfefferle assisted with sequencing. S. Mukherjee advised and assisted with statistical tests. Financial support came from the National Science Foundation (to S.C.A. and J.T.); the American Society of Primatologists (to J.T.); Duke University and the Duke chapter of Sigma Xi (to J.T.); and the Duke Institute for Genome Sciences and Policy (to G.A.W.).

Author Contributions J.T., S.C.A. and G.A.W. designed the study, analysed the results, and wrote the paper. J.T. and S.C.A. collected blood samples; S.C.A. provided the long-term data on Amboseli National Park. J.T. gathered the allelic imbalance and sequence data; A.P., T.F.S. and J.T. collected the transfection assay data; T.F.S. and J.T. collected the genotyping data; A.J.B. and J.T. collected the Hepatocystis data. G.A.W. and S.C.A. provided funding support.

Author information

Author notes

  1. Susan C. Alberts and Gregory A. Wray: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Duke University,

    Jenny Tung, Alexander Primus, Andrew J. Bouley, Susan C. Alberts & Gregory A. Wray

  2. Institute for Genome Sciences and Policy, Duke University,,

    Jenny Tung, Alexander Primus, Tonya F. Severson, Susan C. Alberts & Gregory A. Wray

  3. Department of Evolutionary Anthropology, Duke University, Durham, North Carolina 27708, USA,

    Susan C. Alberts & Gregory A. Wray

  4. Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya

    Susan C. Alberts

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  1. Jenny Tung
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Corresponding author

Correspondence to Jenny Tung.

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Tung, J., Primus, A., Bouley, A. et al. Evolution of a malaria resistance gene in wild primates. Nature 460, 388–391 (2009). https://doi.org/10.1038/nature08149

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