|ADOMAKO-ANKOMAH, YAW - University Of Pittsburgh|
|ENGLISH, ELIZABETH - University Of Pittsburgh|
|DANIELSON, JEFFRY - University Of Pittsburgh|
|PERNAS, LENA - Stanford University School Of Medicine|
|PARKER, MICHELLE - University Of Victoria|
|BOULANGER, MARTIN - University Of Victoria|
|BOYLE, JON - University Of Pittsburgh|
Submitted to: Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2016
Publication Date: 5/1/2016
Citation: Adomako-Ankomah, Y., English, E.D., Danielson, J.J., Pernas, L.F., Parker, M.L., Boulanger, M.J., Dubey, J.P., Boyle, J.P. 2016. Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate. Genetics. 203:283-298.
Interpretive Summary: Toxoplasmosis continues to be a public health problem. It is caused by a sigle celled parasite, Toxoplasma gondii. This parasite can infect all warm blooded hosts, including humans and rodents. Hammondia and Neospora are its closest relatives, so much so that they were considered same parasite, 4 decades ago. Neospora and Hammondia, however have a limited host range and humans and rodents are not its proven hosts. Scientists have started an enquiry in comparing genes among these 3 parasites. In the present study, the authors compared mitochondrial genes that are different in these parasites. These studies will be helpful in understanding genetic basis of pathogenesis, and should be of interest to biologists, and parasitologists.
Technical Abstract: In Toxoplasma gondii, an intracellular parasite of humans and other warm-blooded animals, the ability to associate with host mitochondria (HMA) is driven by a locally expanded gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. The importance of copy number in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we use sequencing and comparative analyses to determine that the MAF1 locus is uniquely amplified in T. gondii compared to its near relatives, and that it displays high variation in copy number and gene content between closely-related T. gondii strains. We used cross-species complementation experiments to determine that the MAF1 locus harbors two classes of distinct paralogs (dubbed “a” and “b”) that differ in their ability to mediate HMA. Specifically, we found that T. gondii and its nearest extant relative Hammondia hammondi harbor “b” paralogs which are HMA-competent, and that this is consistent with a wild type HMA+ phenotype. In contrast Neospora caninum harbors only an “a” paralog and is HMA-. Remarkably, complementation with a single copy of MAF1b, but not MAF1a, is sufficient to confer the HMA phenotype in N. caninum. Moreover, in tissue culture and in a mouse model of infection, MAF1b-expressing (and therefore HMA+) parasites significantly outcompete their MAF1b-null counterparts in vitro and in vivo, an effect that ONLY occurs with MAF1b (and not MAF1a). These data strongly suggest that HMA evolved by neofunctionalization of a duplicate copy of MAF1 in the common ancestor to T. gondii and H. hammondi, and then diversified further via locus expansion in T. gondii. This represents a new example of neofunctionalization of a gene duplicate, and provides strong evidence for the selective advantage that likely maintained, and ultimately fixed, this neofunctionalized gene in T. gondii and H. hammondi.