16-ancient-standing-variation
Supplied working report; original verdicts not validated.
Review status: Needs review. This is an archival source note, not a passed proof.
REPORT.md
# 16 — Selection Acts on Standing Variation (`ancient-standing-variation`) - Source: Incoprea Theory, Volume XXIX (`ancient-standing-variation`) - Claim: Most detectable ancient selection acted on standing variation rather than on new mutations, because adaptation from existing alleles is faster. - Prediction: Selected alleles should predate the selection. - Refutation: Selected alleles appearing with selection would remove the claim. ## Test performed Two-pronged test. **(1) Literature assessment (evidence class b):** reviewed the theory (Orr & Betancourt 2001; Hermisson & Pennings 2005), the genome-wide human data (Schrider & Kern 2017 and its commentary McCoy & Akey 2017), the aDNA case literature (Mathieson et al. 2015; Burger et al. 2020; Itan et al. 2009; Basu Mallick et al. 2013; Kamberov et al. 2013), and the counter-literature (Jensen 2014). **(2) New analysis of published data (evidence class a):** I transcribed the compiled spatiotemporal frequency table of the European lactase-persistence allele (LCT-13910*T) from Supplementary Information S1 of Ségurel & Bon 2017 (*Nat Rev Genet* 18:325–336) — 76 ancient population rows from 25 published aDNA studies plus present-day frequencies — and computed time-binned allele frequencies and the derived-allele count before vs after the onset of the documented strong selection (see `data/`, `figures/`, `code/`). ## Data (sources, URLs, sample sizes) - Ségurel & Bon 2017 supplement S1, "Spatiotemporal frequencies of the European lactase persistence allele" — 76 rows, 580 ancient individuals total (range 1–74 per row), downloaded 30 Oct 2026 from https://static-content.springer.com/esm/art%3A10.1038%2Fnrg.2017.65/MediaObjects/41576_2017_BFnrg201765_MOESM7_ESM.pdf . It compiles Burger 2007; Malmström 2010; Lacan 2011; Nagy 2011; Keller 2012; Plantinga 2012; Krüttli 2014; Skoglund 2014; Lazaridis 2014; Olalde 2014; Sverrisdóttir 2014; Gamba 2014; Günther 2015; Jones 2015; Płoszaj 2015; Witas 2015; Allentoft 2015; Mathieson 2015; Broushaki 2016; Cassidy 2016; Hofmanová 2016; Unterländer 2017; Jones 2017; Mittnik 2017; Mathieson 2017 (bioRxiv); Günther 2017 (bioRxiv). - Schrider & Kern 2017, *Mol Biol Evol* 34:1863–1877 — 1,927 merged sweep candidates across 6 human populations (S/HIC classifier) — https://pmc.ncbi.nlm.nih.gov/articles/PMC5850737/ ; commentary McCoy & Akey 2017, *Genome Biol* 18:139 — https://pmc.ncbi.nlm.nih.gov/articles/PMC5537971/ - Mathieson et al. 2015, *Nature* 528:499–503 — 1,084,781 SNPs in 617 samples (213 ancient) — https://pmc.ncbi.nlm.nih.gov/articles/PMC4918750/ - Burger et al. 2020, *Curr Biol* 30:4307–4315 — 69 additional ancient individuals (Tollense, Mokrin, steppe) — https://discovery.ucl.ac.uk/id/eprint/10110788/ - Itan et al. 2009, *PLoS Comput Biol* 5:e1000491 — ABC model, 200,000 simulations — https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000491 - Basu Mallick et al. 2013, *PLoS Genet* 9:e1003912 (SLC24A5 age 22–28 KYA) — https://pmc.ncbi.nlm.nih.gov/articles/PMC3820762/ - Kamberov et al. 2013, *Cell* 152:691–702 (EDAR 370A arose ~30 KYA) — https://pubmed.ncbi.nlm.nih.gov/23415220/ - Hermisson & Pennings 2005, *Genetics* 169:2335–2352 — https://pmc.ncbi.nlm.nih.gov/articles/PMC1449620/ ## Result (key numbers; reference figure files) **How much of detectable selection is on standing variation?** Schrider & Kern 2017 classified 1,776 of 1,927 sweep candidates (92.2%) as soft sweeps across six human populations; hard sweeps were a small minority and were rarer in African than non-African populations. The paper's own section title is "The Majority of Sweeps in Humans Resemble Selection on Standing Variation." Important caveat from the paper itself: S/HIC cannot fully distinguish selection on standing variation from recurrent *de novo* mutation or gene conversion, and the method's sweep fraction is contested (Jensen 2014). So 92.2% is an upper bound on the standing-variation share, not a clean measurement. **Do selected alleles predate the selection (aDNA check)?** - *LCT-13910*T (lactase persistence):* the compiled ancient data show the derived allele essentially absent or at trace frequency for millennia — n-weighted frequency 1.1% in samples 8–14 kya, 5.0% at 5–8 kya, 6.6% at 4–5 kya, 6.9% at 3–4 kya — then a sustained rise only in the last ~2 millennia (14.9% at 2–3 kya, 32.2% at 1–2 kya, 29.4% at 0–1 kya; present-day 36–96% by region). Across the whole compilation, 292 individuals predating 4,000 BP carry 12.4 derived copies (4.3%) vs 70.3 derived copies (22.8%) among 308 individuals postdating 4,000 BP. The earliest derived copies predate the main rise: one heterozygous Villabruna individual at ~10,090–9,460 BP, Malmström's 5% at 4,800–4,200 BP, and Mathieson's earliest appearance in a Bell Beaker individual ~2300–2200 BCE. Mathieson et al. 2015 state "an appreciable frequency of lactase persistence in Europe only dates to the last four thousand years"; Burger et al. 2020 estimate s = 0.06 with strong selection ongoing over the last 3,000 years. Itan et al. 2009 place the origin of LP/dairying coevolution at ~7,441 BP (95% CI 6,256–8,683). The selected allele therefore predates the selection episode by roughly 1,000–6,000+ years depending on which origin estimate is used. *(Nuance: the allele was at very low frequency at selection onset — near the standing-variation/de-novo boundary — but it did exist first.)* - *SLC24A5 (A111T, light skin):* the derived allele coalesces 22–28 KYA (Basu Mallick et al. 2013) and is already ~fixed in Anatolian Neolithic samples ~8,400–8,300 BP, reaching ~0.9 in Early Neolithic Europe largely by migration (Mathieson et al. 2015). The allele predates any inferred selection by tens of millennia. - *EDAR V370A:* arose ~30 KYA (Kamberov et al. 2013) and is present (3 of 6 heterozygotes) in Scandinavian hunter-gatherers at Motala ~7,700 BP (Mathieson et al. 2015) — long before the sweep that made it common in East Asians/Native Americans. Figure: [figures/allele_age_vs_selection.png](figures/allele_age_vs_selection.png) — left panel: LCT-13910*T frequency through time (points = ancient populations sized by n; red line = n-weighted time bins; stars = present-day); right panel: allele-origin range vs earliest "already common" date for the three aDNA case loci, showing the allele-age–selection-onset lag. ## Verdict **Support** — for the well-characterized cases the data could reach, selected alleles predate their selection: LCT-13910*T existed (at low frequency) for millennia before its ~4,000–3,000-year-old rise, and SLC24A5/EDAR origins precede their selection by 20,000+ years, matching the posted prediction. Genome-wide, 92.2% of Schrider & Kern's 2017 human sweep calls are soft, consistent with adaptation commonly using pre-existing alleles. This is a working assessment, not proof: the soft-sweep share is method-dependent and contested, and "soft" does not strictly equal "standing variation" (recurrent mutation can mimic it). ## Limitations - S/HIC's 92.2% soft fraction cannot separate standing variation from recurrent de novo mutation or gene conversion (acknowledged by the authors), and false-positive rates of ML sweep callers are debated (Jensen 2014; Harris & Jensen style critiques). Association of "soft" with "standing" is interpretive. - The aDNA cases are a handful of famous loci (ascertainment/celebrity bias); they show the claim holds where testable, not that it holds genome-wide. - LCT-13910*T sits near the standing-variation/de-novo boundary (very rare before 4 kya); different authors classify it differently. - Frequency time series mix PCR-typed and genome-sequenced samples with different call quality; the 0.5 Villabruna value is a single low-count individual. - Peter & Slatkin 2013 (listed in the notebook) concerns range-expansion footprints that can mimic sweeps — a demographic confound for genome scans, cited here only as a caveat source. - Ancient selection inferences assume approximate continuity between ancient and modern populations (admixture can mimic frequency change — e.g., SLC24A5's rise was partly migration). ## References - Schrider & Kern 2017, *Mol Biol Evol* 34:1863–1877. https://pmc.ncbi.nlm.nih.gov/articles/PMC5850737/ - McCoy & Akey 2017, *Genome Biol* 18:139. https://pmc.ncbi.nlm.nih.gov/articles/PMC5537971/ - Mathieson et al. 2015, *Nature* 528:499–503. https://pmc.ncbi.nlm.nih.gov/articles/PMC4918750/ - Ségurel & Bon 2017, *Nat Rev Genet* 18:325–336 (suppl. S1). https://static-content.springer.com/esm/art%3A10.1038%2Fnrg.2017.65/MediaObjects/41576_2017_BFnrg201765_MOESM7_ESM.pdf - Burger et al. 2020, *Curr Biol* 30:4307–4315. https://doi.org/10.1016/j.cub.2020.08.033 (accepted MS: https://discovery.ucl.ac.uk/id/eprint/10110788/) - Itan et al. 2009, *PLoS Comput Biol* 5:e1000491. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000491 - Basu Mallick et al. 2013, *PLoS Genet* 9:e1003912. https://pmc.ncbi.nlm.nih.gov/articles/PMC3820762/ - Kamberov et al. 2013, *Cell* 152:691–702. https://pubmed.ncbi.nlm.nih.gov/23415220/ - Hermisson & Pennings 2005, *Genetics* 169:2335–2352. https://pmc.ncbi.nlm.nih.gov/articles/PMC1449620/ - Orr & Betancourt 2001, *Genetics* 157:875–884. https://pubmed.ncbi.nlm.nih.gov/11157004/ - Jensen 2014, *Nat Commun* 5:5281. https://doi.org/10.1038/ncomms6281 - Garud et al. 2015, *PLoS Genet* 11:e1005004. https://pmc.ncbi.nlm.nih.gov/articles/PMC4338236/ - Peter & Slatkin 2013, *Evolution* 67:3274–3289. https://doi.org/10.1111/evo.12202 All URLs accessed 30 October 2026.