Intertwining genome organisation and gene regulation in Leishmania.

Leishmania are trypanosomatid parasites whose unorthodox genomes challenge classical views of how DNA replication and gene expression are regulated in eukaryotes. Within this unconventional genomic context, chromosome replication, constitutive polycistronic transcription, chromatin architecture, and noncoding RNAs emerge not as discrete regulatory layers but as mutually dependent determinants of gene expression and genome stability. Recent advances have also uncovered an unexpected interconnection between Leishmania's evolutionarily divergent replication stress response machinery and its peculiar genomic organisation and expression. In this review, we discuss how recent discoveries are reshaping our understanding of genome biology in Leishmania and highlight the integration of DNA replication, gene expression, and genome maintenance as a unifying principle underlying the remarkable capacity of these parasites to adapt and evolve.