h the true error rate at these low levels cannot be accurately calculated due to genuine sequence di?erences between this Neandertal and the human reference.
A truly impressive low error rate in the best case – which here involves sequencing many copies of the same sites, generating “deep coverage”. But consider: the average sequence divergence between two humans is around 0.1 percent. With a total error rate of 0.09 percent, there would be nearly as many erroneous differences as real ones between an ancient genome and the modern reference. And sequencing two ancient genomes would double the errors, so that the apparent genetic differences would be roughly three times the actual value.
Even deeper coverage will be necessary, hopefully reducing error rates further. This may lead to a hypothesis-testing approach for sequence differences found in Neandertal genomes, as the false positives are sifted out of the data. It’s going to take some creative population genetics to deal with this problem, as we try to analyze the data from these ancient specimens.
Briggs AW, Stenzel U, Meyer M, Krause J, Kircher M, Pääbo S. 2009. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res (advance) doi:10.1093/nar/gkp1163