Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites

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.

R-loops acted on by RNase H1 are a determinant of chromosome length-associated DNA replication timing and genome stability inLeishmania

“…In this regard, we cannot currently say in Leishmania if R-loops might be allele-specific and provide a form of potentially non-coding RNA-associated ASARs that contribute to replication timing 55 . However, it is notable that L. major chromosome 31, which is always greater than diploid 156 , does not follow the global pattern of R-loop or SNS-seq density, or of chromatin accessibility. In T. brucei , monoallelic transcription of one the ∼15 telomeric VSG expression sites 157, 158 is intimately tied with DNA replication timing 72 , and mutation of RNase H1 or RNaseH2A impairs this expression control, an effect that is associated with increased R-loops across all VSG expression sites 98, 100 .…”