Authors

SA Pimenta-Carvalho⁵; LV Almeida⁵; A Coqueiro-dos-Santos⁵; RP Baptista³; GF Rodrigues-Luiz⁴; CN Costa⁷; MS Cardoso⁵; CA Grace⁶; DC Jeffares¹; R McCulloch²; D Bartholomeu⁵; JL Reis-Cunha⁶;  ¹ University of York, UK;  ² Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, UK;  ³ University of Georgia, United States;  ⁴ Campinas State University (UNICAMP), Brazil;  ⁵ Federal University of Minas Gerais - UFMG, Brazil;  ⁶ York Biomedical Research Institute, Department of Biology, University of York, UK;  ⁷ Federal University of Piauí, Teresina, Brazil

Discussion

Aneuploidy, the presence of an aberrant number of chromosomes in a cell, usually results in severe abnormalities in multicellular eukaryotes as humans. However, some unicellular eukaryotes rely on aneuploidy as a mechanism to allow rapid adaptation to changing environments, having a positive fitness in stress conditions and promoting drug resistance. Aneuploidies have been largely described in protozoan parasites as Leishmania and Trypanosoma cruzi,  where duplicated chromosomes vary in different hosts and can promote drug resistance. Interestingly, the closely related parasite Trypanosoma brucei is mainly euploid. Hence, to evaluate if aneuploidies are an ancestral or a recent feature in trypanosomatids we estimated the chromosome copy number variation in 13 Trypanosomatidae species, including Angomonas, Crithidia, Leptomonas and T. vivax, using whole genome sequencing and read depth coverage variations. Aside from T. brucei, T. evansi and T. vivax, all the remaining species have evidence of aneuploidies, including Paratrypanosoma confusum, an early-branching trypanosomatid, indicating that it is an ancestral character in these parasites. The presence of aneuploidies could be detrimental in T. brucei clade, as their genome is packed in a lower number of larger chromosomes. Next, we evaluated if there were consistent chromosomal duplications in the evaluated species. Leishmania chromosome 31 is constantly supernumerary, a fact reassured by our analysis of ~200 isolates from L. donovani and L. infantum populations in Africa, Asia and Brazil. This chromosome had an increased nucleotide diversity (π), which is expected, as having extra copies per cell results in more sites to be randomly mutated. In addition, redundant copies of genes could allow a rapid adaptation and diversification without loss of function. Regarding the other trypanosomatid species, the chromosomes that have most of its genes orthologous to Leishmania chromosome 31 were also consistently supernumerary, even in the euploid T. brucei clade where regions of this chromosome are duplicated into two sequences, chromosomes 4 and 8. This suggests that there are important genes enrolled in the parasite survival in these sequences. We evaluated the function of these shared duplicated genes and we found genes involved in parasite’s osmoregulation and response to stress, as well as diverse cytoskeleton mediated processes such as cell morphogenesis, flagellar motility and cell division. We evaluated the function of these shared duplicated genes and we found genes involved in housekeeping functions as osmoregulation and response to stress, diverse cytoskeleton mediated processes such as cell morphogenesis, flagellar motility and cell division, energy obtaining pathways, host immune system evasion, infectivity and intracellular trafficking. We are now evaluating species-specific genes that were inserted in these duplicated regions specifically in each protozoan, as those can be important to each parasite adaptation.