# Evolutionary dynamics of zoonotic malaria

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $620,102

## Abstract

Dozens of malaria species, of the genus Plasmodium, infect human and nonhuman primates worldwide. At
least eight of these parasite species have moved from primate reservoirs into human populations, including
historical host expansion of P. vivax and P. falciparum, the two primary malaria-causing agents in humans
worldwide. As we make progress towards elimination of these common malaria parasites, emerging host
switches or expansions that introduce new or rare malaria parasites into human population are an increasing
barrier to global elimination. Indeed, in parts of Southeast Asia, a zoonotic malaria parasite is now the main
cause of clinical malaria. The lack of genomic resources for zoonotic malaria strains, particularly from wild
primates, has been a major barrier to understanding the emergence of malaria parasites and their risk for
spread in human populations. Using the emerging zoonotic parasite from Brazil, P. simium, as a case study,
we combine whole-genome sequencing of multiple parasite and their host populations to characterize the
genetic basis of host specificity and evolution in malaria parasites. P. simium is an ideal system because it is a
close relative of the well-studied P. vivax, and importantly, has recently shifted host ranges twice, first from
historical human P. vivax into primates, and more recently back into humans. To interpret this new genomic
data, we will combine experimental techniques with development of a whole-genome simulation framework
that incorporated aspects of parasite lifecycle to better interpret neutral genetic diversity. This opens up recent
developments in simulation-based inference techniques that we will use to infer the population history of South
American malaria parasites, the timing of zoonoses, and identify loci under selection in multiple hosts. The
function of candidate loci identified from computational approaches will then be tested with a specially-
developed transgenic line expressing P. simium genes and computational modeling of protein structures from
host and parasites. In sum, we combine insights from parasite genomics with complementary analyses of
whole genomes from their wild primate hosts—from computational methods development to functional
experiments—giving insight into the selective pressures that parasites face inside hosts and host-specific
susceptibility.

## Key facts

- **NIH application ID:** 10768776
- **Project number:** 5R01AI175622-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Amy Goldberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $620,102
- **Award type:** 5
- **Project period:** 2023-01-25 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768776

## Citation

> US National Institutes of Health, RePORTER application 10768776, Evolutionary dynamics of zoonotic malaria (5R01AI175622-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10768776. Licensed CC0.

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