|Khan, Asis - WASHINGTON UNIV ST. LOUIS|
|Taylor, Sonya - WASHINGTON UNIV ST. LOUIS|
|Ajioka, James - UNIV OF CAMBRIDGE, UK|
|Sibley, David - WASHINGTON UNIV ST. LOUIS|
Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 3, 2009
Publication Date: March 6, 2009
Repository URL: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000404
Citation: Khan, A., Taylor, S., Ajioka, J., Rosenthal, B.M., Sibley, D. 2009. Selection at a single Locus leads to widespread expansion of Toxoplasma gondii lineages that are virulent in mice. PLoS Genetics. 5(3): e1000404. Interpretive Summary: Rarely is it possible to determine what genetic factors increase the transmissibility and success of particular parasite strains. This study examined the evolutionary history and functional significance of variation in a particular gene product secreted into host cells by Toxoplasma gondii, a widespread parasite of animals and people. We established that parasites otherwise indisposed virulence became lethal to mice when supplemented with the version of the ROP18 gene found in virulent strains. We identified marked sequence differences between these alternative gene versions (alleles). Interestingly, we also found differences in the extent of expression of this gene's product among natural isolates of the parasite, reflected in the degree of parasite virulence. By comparing this genomic region to a related parasite, we inferred that expression of this gene product has increased over time in virulent parasites. Our findings demonstrate that pathogens can evolve towards stable expression of enhanced virulence due to changes in gene expression at a single locus, which has consequences for understanding transmission dynamics and diseases caused by infectious agents.
Technical Abstract: Adaptations that increase pathogen transmission among animal hosts may affect the spectrum of human disease, however the underlying mechanisms are rarely understood. We elucidated the evolutionary history and functional consequences of diversification in the serine/threonine kinase ROP18, a major pathogenicity determinant of the intracellular parasite Toxoplasma gondii. ROP18 is secreted into the host cell during invasion and its kinase activity enhances parasite growth and virulence. Historical loss of an upstream regulatory element increased ROP18 expression, exposing it to newfound diversifying selection, and resulting in greatly enhanced virulence. The resulting virulent allele of ROP18 is widespread among natural parasite populations where it has driven the successful expansion of T. gondii, demonstrating that sweeping changes can result from alterations in a single gene.