Peaks cloaked in the mist: The landscape of mammalian replication origins

Replication of mammalian genomes starts at sites termed replication origins, which historically have been difficult to locate as a result of large genome sizes, limited power of genetic identification schemes, and rareness and fragility of initiation intermediates. However, origins are now mapped by the thousands using microarrays and sequencing techniques. Independent studies show modest concordance, suggesting that mammalian origins can form at any DNA sequence but are suppressed by read-through transcription or that they can overlap the 5′ end or even the entire gene. These results require a critical reevaluation of whether origins form at specific DNA elements and/or epigenetic signals or require no such determinants.