tag:blogger.com,1999:blog-37148773.post7910241951792986253..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Human Mutation RatesLarry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-37148773.post-59644625449138838312010-11-10T04:17:55.342-05:002010-11-10T04:17:55.342-05:00... and of course mutation is stochastic. As, inde...... and of course mutation is stochastic. As, indeed, is the actual number of cell divisions separating each sperm from its originating zygote. Further, the relationship between paternal error rate and cell divisions is not linear - older parents make even more mistakes, so 13 generations clustering around the mean would give a different mutation rate from one with the same number of replications but higher variance. <br /><br />All of this makes extrapolation from the Y study, or even regarding it as confirmatory of the in vitro error rate, a little premature. 4 mutations from 13 generations of a 400-cell-cycle 10.15Mb unit is well within the bounds of expectation for mutation rates from under half to over 1.5 times the in vitro figure if the division count is right, and likewise for 2/3rds to twice the division count if the mutation rate is right, and sundry combinations thereof. And of course we are light by any mutations that were 'corrected' by selection - population size is irrelevant here; we are looking at two surviving Y chromosomes. <br /><br />So yes, I think there is some work to be done before we would need to adjust divergence times!Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-1017944380365091742010-11-05T05:21:54.752-04:002010-11-05T05:21:54.752-04:00It seems common to omit the effects of recombinati...It seems common to omit the effects of recombination and non-cell-cycle mutagenesis from the calculation. If we just use copying error/repair rates and the number of divisions in the germ line (presumably averaged between male and female) and generation time (... same again?), we are tacitly assuming that recombinational mutation and interphase attrition can be ignored, and that the only significant source of mutation is mitotic (or early meiotic prophase) DNA copying and repair error. Which may prove to be the case, but there is for example a correlation between SNPs and regions of high recombination (eg Lercher & Hurst, Trends in Genetics 18/7 pp 337-340). This would also interact with generation time - shorter generations = a higher proportion of recombinational mutation per cycle. <br /><br />More dubious is the assertion that the Y study 'confirms theory'. If we have a rate of 130 mutations per (gender-not-specified) individual, I would not expect the rate on a Y, with a very individualistic approach to homologous repair and a faster turnover in the germ line, to be in the same ball park. Confirmation bias?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-44412785609073228452010-11-05T00:13:50.949-04:002010-11-05T00:13:50.949-04:00Doesn't uncertainty in effective ancestral pop...Doesn't uncertainty in effective ancestral population size trump these little two-fold uncertainties in mutation rate and number of generations?DKnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-65626078108736509952010-11-04T13:15:03.809-04:002010-11-04T13:15:03.809-04:00I agree that the Roach et al. (2010) estimate isn&...I agree that the Roach et al. (2010) estimate isn't very reliable, which is where I left it last spring. But I think that the Lynch (2010) estimate probably is fairly reliable, and it is essentially the same value.John Hawkshttps://www.blogger.com/profile/17027862713126904206noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-5990353789312611002010-11-04T13:05:55.131-04:002010-11-04T13:05:55.131-04:00We usually take fixed points, but there's an i...We usually take fixed points, but there's an increasing trend to authors using uncalibrated clocks with just some vague assumptions about mutation. Particularly in species with poorly documented fossil records. I can think of one pertinent example where an author uses a generic substitution rate to date divergences in some cervids, which happen to line up with climatic events. But what's left unmentioned is that those dates would be sensitive to small changes in the mutation rate.TwoYakshttps://www.blogger.com/profile/18004999495564178762noreply@blogger.com