Underreplication

Underreplication is a genomic phenomenon in which certain regions are replicated to a lower copy number than the rest of the genome. It is most extensively studied in organisms and tissues that undergo endoreplication or have polyploid chromatin, such as the salivary gland cells of Drosophila. In these tissues, portions of the genome—often late-replicating heterochromatin and gene-poor areas—do not achieve full replication across successive S phases, leading to regional underrepresentation on the polytene chromosome maps and in copy-number measurements.

Mechanistically, underreplication correlates with replication timing and fork progression. Late-replicating domains are more prone to fork slowing or stalling, and in Drosophila, the SUUR protein promotes this fork inhibition in specific chromatin regions, reinforcing underreplication. Chromatin structure, origin distribution, and developmental regulation all contribute to where and when UR occurs. The phenomenon is therefore highly locus- and tissue-specific rather than uniform across the genome.

Consequences and detection methods reflect its impact on genome analyses. UR can bias sequencing-based copy-number assessments, producing lower read depth in affected regions and complicating interpretation of gene dosage. It is often identified cytogenetically in polytene chromosomes as gaps or underrepresented bands, and corroborated by sequencing depth comparisons to a reference genome or targeted molecular assays.

While well characterized in Drosophila, underreplication is discussed as a feature of endoreplicating cells in other species and contexts. It is distinct from DNA deletions or losses and represents regulated replication dynamics within specific chromatin domains.