Mechanisms of life cycle simplification in African trypanosomes

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Summary

The study analyzed the genomes of African trypanosomes to identify molecular adaptations contributing to their simplified lifecycle, enabling them to expand their geographic range beyond the tsetse belt.

Highlights

• The study analyzed 83 T. brucei isolates from diverse hosts, including humans, cattle, equids, camels, and tsetse.
• Monomorphic T. brucei isolates have reduced or lost their ability to form stumpy forms, which are pre-adapted for uptake by tsetse flies.
• The study identified mutations in discrete genes that hinder pleomorphic phenotypes, including Tb927.2.4020, Tb927.5.2580, and Tb927.11.3400.
• The study found that monomorphic T. brucei isolates have a reduced or absent mitochondrial genome (kDNA).
• The study identified changes in gene expression associated with the transition from pleomorphism to monomorphism.
• The study found that the downregulation of RNA regulators, such as RBP10 and ZC3H20, is important in the initial development of monomorphism.
• The study identified a trajectory of events that simplify the lifecycle in emergent and established monomorphic trypanosomes.

Key Insights

• The study suggests that monomorphism in T. brucei is initially reversible via changes in the expression of post-transcriptional regulators, allowing parasites to sustain transmission flexibility.
• The accumulation of deleterious mutations in key QS genes, independent gradual loss of kDNA, and accumulation of mutations in the mitoproteome eventually lock parasites into an obligate asexual/monomorphic lifecycle.
• The study highlights the importance of detecting emergent monomorphic clades, particularly where tsetse population control strategies and climate change are modifying the range of the vector.
• The study provides diagnostic tools to detect and anticipate the threat of monomorphic T. brucei.
• The study suggests that the generation of stumpy forms is maintained in T. brucei populations to optimize transmission by tsetse flies.
• The study found that monomorphic T. brucei isolates have a reduced or absent mitochondrial genome (kDNA), which is a secondary consequence of their simplified lifecycle.
• The study identified a common transcriptome trajectory among distinct selected lines, indicating a shared mechanism of monomorphism development.

Mindmap

Citation

Oldrieve, G. R., Venter, F., Cayla, M., Verney, M., Hébert, L., Geerts, M., Van Reet, N., & Matthews, K. R. (2024). Mechanisms of life cycle simplification in African trypanosomes. In Nature Communications (Vol. 15, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41467-024-54555-w