Scientists from the Centre for Genomic Regulation in Barcelona and Harvard Medical School have discovered a surprisingly fragile region in human DNA that is highly prone to errors during the earliest moments of life. Their study, published in Nature Communications, identifies a mutation-sensitive area within the first 100 base pairs of transcription start sites—the segments where genes begin their work.
These genetic slip-ups, known as mosaic mutations, occur after the zygote forms and cells begin to divide rapidly. Unlike inherited mutations, which are present in every cell, mosaic mutations appear in scattered patches across the body, making them extremely hard to detect.
How this discovery changes our understanding of mutations
Lead author Donate Weghorn describes these regions as “among the most functionally important parts of the human genome” and notes that discovering a new source of human mutations “doesn’t happen often”. The research team analysed more than 2.25 lakh transcription start sites using the Genome Aggregation Database and the U.K. Biobank, comparing this information with data from eleven detailed family studies.
Their findings revealed that this newly identified mutation hotspot affects genes linked to cancer pathways, brain development and limb growth—areas where even small genetic shifts can produce major consequences.
Mosaic mutations vs chimerism
While mosaic mutations come from a single fertilised egg, chimerism arises when two fertilised eggs fuse. Chimeric cells tend to be distributed more evenly throughout the body, but mosaic mutations occur in irregular clusters. Many people carrying these mutations may show no symptoms, yet the errors can be passed to their children, where they replicate throughout every developing cell.
Nature’s clean-up mechanism
Interestingly, the study found that rare, newly formed variations were packed densely around this fragile region, but the pattern weakened among more common variants. This suggests that natural selection steadily removes harmful mutations over generations.
Researchers say this discovery will improve genetic models, which may currently underestimate mutation rates in these critical regions. Better models could help explain developmental disorders and refine diagnostic tools.