Calibrating a coalescent simulation of human genome sequence variation
Open accessAbstract
Population genetic models play an important role in human genetic research, connecting empirical observations about sequence variation with hypotheses about underlying historical and biological causes. More specifically, models are used to compare empirical measures of sequence variation, linkage disequilibrium (LD), and selection to expectations under a “null” distribution. In the absence of detailed information about human demographic history, and about variation in mutation and recombination rates, simulations have of necessity used arbitrary models, usually simple ones. With the advent of large empirical data sets, it is now possible to calibrate population genetic models with genome-wide data, permitting for the first time the generation of data that are consistent with empirical data across a wide range of characteristics. We present here the first such calibrated model and show that, while still arbitrary, it successfully generates simulated data (for three populations) that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation. No assertion is made about the accuracy of the proposed historical and recombination model, but its ability to generate realistic data meets a long-standing need among geneticists. We anticipate that this model, for which software is publicly available, and others like it will have numerous applications in empirical studies of human genetics.
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The initial stages of European skin lightening occurred in a proto-Eurasian population approximately 30,000 years ago, after the out-of-Africa migration 60,000-70,000 years ago and slightly more recently than the earliest archaeological evidence for anatomically modern humans in Europe approximately 40,000 years ago.
“Our results based on the KITLG gene suggest that the initial stages of European skin lightening occurred in a proto-Eurasian population, approximately 30,000 years ago”
From The timing of pigmentation lightening in Europeans (2013) · cites this paper as Schaffner et al. 2005
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Experimental — accuracy not yet measuredThe demographic model most compatible with the data for European and East Asian populations is a bottleneck scenario, with stronger genetic drift in East Asian populations than European populations.
“Recent studies have shown that the demographic model most compatible with the data for European and East Asian populations is a bottleneck scenario, with stronger genetic drift in East Asian populations than European populations (Schaffner et al. 2005;Voight et al. 2005).”
From The timing of pigmentation lightening in Europeans (2013) · cites this paper as Schaffner et al. 2005
The Discussion’s Table 1 gives the best-fitting simulation a stronger Asian bottleneck (F = 0.067) than European bottleneck (F = 0.020), consistent with greater drift in the Asian lineage. But the Discussion says many other models could fit acceptably and cautions that its parameters are not inferences about real-world history. It therefore does not establish a bottleneck scenario as the uniquely most compatible demographic history. (LLM, conf=0.88)
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- Authors
- Schaffner, S. F., Foo, C., Gabriel, S., Reich, D., Daly, M. J., & Altshuler, D.
- Affiliations
- Broad Institute (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-10-26
- Volume
- 15
- Issue
- 11
- Pages
- 1576-1583
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1310645
- OpenAlex
- W2161644980
- Cited by
- 616
- References
- 31
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 16 · 2022: 13 · 2021: 14 · 2020: 15 · 2019: 33 · 2018: 19 · 2017: 20 · 2016: 45 · 2015: 47 · 2014: 36 · 2013: 49 · 2012: 44
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Broad Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- coalescent simulation, model calibration, linkage disequilibrium, allele frequency, genetic differentiation, recombination rate, mutation rate, human demographic history, population genetic models, simulated data
- MeSH terms
- Computer Simulation, Gene Frequency, Genetics, Population, Humans, Models, Genetic, Genetic Variation, Linkage Disequilibrium, Genome, Human, Evolution, Molecular, Genomics
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