João L. Reis-Cunha1,5, Samuel A. Pimenta-Carvalho2,5, Laila V. Almeida2, Anderson Coqueiro-dos-Santos2, Catarina A. Marques3, Jennifer A. Black3,4, Jeziel Damasceno3, Richard McCulloch3,6, Daniella C. Bartholomeu2,6 and Daniel C. Jeffares1,6 1York Biomedical Research Institute, Department of Biology, University of York, York YO10 5DD, United Kingdom; 2Instituto de Ciências Biológicas, Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil; 3The Wellcome Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow G12 8TA, United Kingdom; 4Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 14049-900, Brazil

↵5 These authors contributed equally to this work.

↵6 These authors contributed equally to this work.

Corresponding author: joao.cunhayork.ac.uk Abstract

Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause neglected tropical diseases, are a relevant group to study aneuploidies. Their life cycle has several stressors that could select for different patterns of chromosomal duplications and/or losses, and their nearly universal use of polycistronic transcription increases their reliance on gene expansion/contraction, as well as post-transcriptional control as mechanisms for gene expression regulation. By evaluating the data from 866 isolates covering seven trypanosomatid genera, we have revealed that aneuploidy tolerance is an ancestral characteristic of trypanosomatids but has a reduced occurrence in a specific monophyletic clade that has undergone large genomic reorganization and chromosomal fusions. We have also identified an ancient chromosomal duplication that was maintained across these parasite's speciation, named collectively as the trypanosomatid ancestral supernumerary chromosome (TASC). TASC has most genes in the same coding strand, is expressed as a disomic chromosome (even having four copies), and has increased potential for functional variation, but it purges highly deleterious mutations more efficiently than other chromosomes. The evidence of stringent control over gene expression in this chromosome suggests that these parasites have adapted to mitigate the fitness cost associated with this ancient chromosomal duplication.

Footnotes

[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278550.123.

Freely available online through the Genome Research Open Access option.

Received September 22, 2023. Accepted March 14, 2024.