The dysgenic effects of modern civilization

I hope that strong AI and practical gene editing becomes a reality before this bleak future kicks in.

GENETICS March 7, 2016 vol. 202 no. 3 869-875; DOI: 10.1534/genetics.115.180471

Mutation and Human Exceptionalism: Our Future Genetic Load

Michael Lynch

Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species. What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention. Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits.

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More Y-chromosome super-fathers

The time estimates are based on a mutation rate of 1x10-9 mutations/bp/year which is ~1/3 higher than mutation rate of Karmin et al.  So the values on the table may be a little lower.

There may be additional founders with recent time depths than shown in the table, e.g., a very shallow clusters within E-M35 (probably E-V13?) and a couple of shallow clusters within I-P215

Also of interest is the fact that Greeks and Anatolian Turks do not show evidence of the recent Y-chromosomal bottleneck:

The plots are consistent with patterns seen in the relative numbers of singletons, described above, in that the Saami and Palestinians show markedly different demographic histories compared with the rest, featuring very recent reductions, while the Turks and Greeks show evidence of general expansion, with increased growth rate around 14 KYA. A different pattern is seen in the remaining majority (13/17) of populations, which share remarkably similar histories featuring a minimum effective population size ~2.1–4.2 KYA (considering the 95% confidence intervals (CIs) reported in Supplementary Table 4), followed by expansion to the present.

Related:

• Y chromosome super-fathers 
• Bottleneck in human Y-chromosomes in the last 10,000 years

Nature Communications 6, Article number: 7152 doi:10.1038/ncomms8152

Large-scale recent expansion of European patrilineages shown by population resequencing

Chiara Batini, Pille Hallast et al.

The proportion of Europeans descending from Neolithic farmers ~10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ~2.1–4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.

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Mutation rate again (Lipson et al. 2015)

This estimate is in-between 1.2 and 2.5x10-8, the two most quoted values for this parameter. It seems like such an important number that I'm wondering if it would be possible to brute force estimate it. Maybe people who have whole genomes of parents-offspring should get together and do the mother of all meta-analyses to pin down this number.

From the paper:

For example, a recent method for estimating population split times from coalescent rates placed the median split of African from non-African populations at 60–80 ky and the split of Native Americans from East Asians at ∼ 20 ky, both assuming a per-generation mutation rate of 1.25 × 10−8 and an average generation interval of 30 years [28]. [...] Using our inferred rate also makes the dates more recent, but only by a factor of about 1.3 rather than 2, i.e., ∼ 46–61 and 15 ky (with some associated uncertainty both from the model and from our estimated rate), neither of which contradicts external evidence.

The first of these estimated splits overlaps the dates of estimated Neandertal admixture by the Ust' Ishim and Kostenki papers. For a variety of reasons that I've repeated ad nauseam, I think that the split of Africans from non-Africans first happened about 100ka with Out-of-Africa-into-Arabia. But, if there was back-migration into Africa, maybe this can be brought down. The 15ky value for the East Asian/Native America split seems too young: it's as late as could plausibly maintained for the colonization of the Americas, but the split of the two must have happened some time before that (because the ancestors of Native Americans and East Asians would have split long before a group of them made the crossing into the Americas).

bioRxiv http://dx.doi.org/10.1101/015560

Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes

Mark Lipson et al.

The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Classical methods based on sequence divergence have yielded significantly larger values than more recent approaches based on counting de novo mutations in family pedigrees. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.65 +/- 0.10 x 10^(-8) mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.

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Everything you ever wanted to know about mutation rate in humans

Annual Review of Genomics and Human Genetics Vol. 15: 47-70 (Volume publication date August 2014)

Determinants of Mutation Rate Variation in the Human Germline

Laure Ségurel, Minyoung J. Wyman, and Molly Przeworski

Because germline mutations are the source of all evolutionary adaptations and heritable diseases, characterizing their properties and the rate at which they arise across individuals is of fundamental importance for human genetics. After decades during which estimates were based on indirect approaches, notably on inferences from evolutionary patterns, it is now feasible to count de novo mutations in transmissions from parents to offspring. Surprisingly, this direct approach yields a mutation rate that is twofold lower than previous estimates, calling into question our understanding of the chronology of human evolution and raising the possibility that mutation rates have evolved relatively rapidly. Here, we bring together insights from studies of human genetics and molecular evolution, focusing on where they conflict and what the discrepancies tell us about important open questions. We begin by outlining various methods for studying the properties of mutations in humans. We review what we have learned from their applications about genomic factors that influence mutation rates and the effects of sex, age, and other sources of interindividual variation. We then consider the mutation rate as a product of evolution and discuss how and why it may have changed over time in primates.

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