Nature Genetics (2011) doi:10.1038/ng.862
- The authors find substantial family-related variability of the mutation rate. It may be worthwhile to determine whether the mutation rate is a constant across the geographical range of H. sapiens; it is not inconceivable that, if there are family differences in mutability, there may also be population differences.
- The authors estimate the human-chimp divergence at 7 million years. This is reasonably close to the 6.5 million years in last year's papers about Neandertal/Denisovan admixture in modern years, but it is worthwhile to re-examine all past papers with dates dependent on this calibration point. Until now, we had to "fix" human/chimp divergence, and express divergences within Homo and within Homo sapiens as a fraction of that divergence, but our newfound ability to study whole genomes of 1st degree relatives -and soon many more of those- will make it possible to measure the rate directly and not depend on any calibration based on paleontological data.
Variation in genome-wide mutation rates within and between human families
Donald F Conrad et al.
J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline1. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans2, 3. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.