A recent flurry of reports correlates replication timing (RT) with mutation 
rates during both evolution and cancer. Specifically, point mutations and copy 
number losses correlate with late replication, while copy number gains and other 
rearrangements correlate with early replication. In some cases, plausible 
mechanisms have been proposed. Point mutation rates may reflect temporal 
variation in repair mechanisms. Transcription-induced double-strand breaks are 
expected to occur in transcriptionally active early replicating chromatin. 
Fusion partners are generally in close proximity, and chromatin in close 
proximity replicates at similar times. However, temporal enrichment of copy 
number gains and losses remains an enigma. Moreover, many conclusions are 
compromised by a lack of matched RT and sequence datasets, the filtering out of 
developmental variation in RT, and the use of somatic cell lines to make 
inferences about germline evolution.