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### Widespread RNA and DNA Sequence Differences in the Human Transcriptome Li et al Science . 2011;333:53–58.New genomic studies show that the transfer of genetic information from DNA to RNA within humans is not very faithful. If true, frequent, or purposeful, then the implications for human health and disease are significant, but the burden of proof required is significant. Commentary: Molecular biology and genetics has a “central dogma.” First postulated by Francis Crick1,2 in 1958, shortly after the discovery of the double helix, it states that the molecular transfer or flow of genetic information occurs only as DNA→RNA→ protein. This argument is intrinsic to our understanding of genotypes, phenotypes, and human disease. The central “dogma,” a word whose precise meaning Crick acknowledged he did not precisely know3 and that could have been given the less glamorous moniker “hypothesis,” is frequently misunderstood as also implying high accuracy or even inflexibility.2 We now know that genetic information flow can be sometimes corrupted and can also occur in other directions in particular biological systems.A recent study by Li and colleagues,4 from the laboratory of Vivian Cheung at the University of Pennsylvania, now demonstrates apparent widespread DNA→RNA sequence differences in humans. The experiments they conducted involved sequencing reverse-transcribed RNA from cultured B cells isolated from 27 different humans and comparing them with their host genome sequences. Surprisingly, after appropriate quality controls, they discovered numerous base positions at which the RNA sequence was different from the DNA sequence in multiple molecules, a phenomenon they refer to as RDD (RNA-DNA difference). Specifically, they identified 28766 RDDs in the 27 individuals at 10210 exonic sites within 4741 genes. Each individual had high-quality RNA-based sequence data at 9.8 million sites: so, RDD was detected at a rate of 1.1×10−4 per exonic site (base) across human genes. Interestingly, they observed all 12 types …

Widespread Promiscuous Genetic Information Transfer From DNA to RNA