1. Nuclearly encoded mitochondrial genes and their role in the adaptation to mechanical transmission in African trypanosomes.
- Author
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Greif, Gonzalo, Rodríguez, Matias, Robello, Carlos, and Alvarez Valin, Fernando
- Subjects
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MITOCHONDRIAL DNA , *MITOCHONDRIA , *AFRICAN trypanosomiasis , *LIFE cycles (Biology) , *TSETSE-flies , *GENOME editing , *PLANT mitochondria , *PHYSIOLOGICAL adaptation - Abstract
African trypanosomiasis comprises a group of diseases caused by various species of Trypanosoma of the Salivaria group, which affect both humans (sleeping sickness) and domestic and wild animals (Nagana). Trypanosoma vivax, the main cause of Nagana, is naturally vectored by the tsetse fly, whose distribution is restricted to the sub-Saharan zone of the African continent. In the proboscis of these insects, T. vivax undergoes a stage of its life cycle (epimastigote) of rapid cell division. During this replicative phase, trypanosomes need to carry out oxidative phosphorylation, due to the lack of nutrients in this environment. In contrast, in the stage of the life cycle that occurs in mammalian blood (rich in glucose), glycolysis is the almost exclusive source of energy supply. Thus, the respiratory chain plays a key role exclusively during passage through the insect vector. T. vixax was introduced to the American continent several centuries ago, where due to the absence of its natural vector (the tsetse fly), these parasites are transmitted by several species of hematophagous flies (Tabanidae and Stomoxys). These flies function as exclusively mechanical vectors (similar to an "infected needle"), so the parasite does not go through the replicative epimastigote phase that depends on mitochondrial respiration. This absence of respiratory requirement led us to propose that the mitochondrial genome of T. vivax, which encodes some protein subunits of the respiratory chain, should have undergone changes in response to the new lifestyle based on mechanical transmission. Analysis of the mitochondrial genomes of Venezuelan and one African strain (Y486) allowed us to identify several loss-of-function mutations (reading frame shifts). The mitochondrial editing system of these trypanosomes was drastically reduced in American T. vivax, with loss of guide RNAs linked to most of the mitochondrial genes that require such modifications. Expanding the range of American strains, we observed that most likely the incursion into America occurred several times, and in each of these independently occurred degradation of the coding capacity of the mitochondrial genomes. We then analyzed the adaptation to mechanical transmission of mitochondrial genes encoded in the nucleus (about 700 genes) and it is to be expected that many of these genes are changing in response to this drastic "environmental" modification. This same process analyzed in several strains of T. vivax that have acquired adaptation to mechanical transmission independently, as well as in T. evansi, offers the opportunity to study an adaptive process occurring simultaneously and independently in several lineages. Another affected system is the variable surface protein (VSG) coding system, associated with antigenic variation, since mechanical transmission implies not going through the phase in which parasites perform recombination (epimastigote). This surely affects the capacity to generate variability and has promoted important changes, which is reflected in the fact that some American strains present a substantial reduction of genomic regions encoding VSG genes. [ABSTRACT FROM AUTHOR]
- Published
- 2022