A test for ancient selective sweeps and an application to candidate sites in modern humans
Open accessAbstract
We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal-Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.
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Inferences from the signature of selective sweeps will only be possible for very recent speciation events because the genomic footprint of selection is rapidly eroded by mutation and recombination.
“In addition, inferences from the signature of selective sweeps will only be possible for very recent speciation events because the genomic footprint of selection is rapidly eroded by mutation and recombination (Racimo et al., 2014).”
From Genomics of plant speciation (2023) · cites this paper as Racimo et al., 2014
The Introduction (page not provided) says some conventional sweep signatures lose power or do not persist long after a sweep, making ancient selection difficult to detect. But the Results and Materials and Methods (pages not provided) describe statistics useful for detecting ancient sweeps. The paper therefore contradicts the claim that sweep-based inference is possible only for very recent speciation events. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredERBB4 is one of many neural crest-related genes associated with selective signals in AMH, some of which show fixed or nearly fixed amino acid changes compared to Neanderthals.
“ERBB4 is one of many neural crest-related genes associated with selective signals in AMH (e.g., SNAI2 [44], CITED2 [44], PRDM10 [46, 78], and others [38]), some of which show fixed or nearly fixed amino acid changes compared to Neanderthals.”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [78]
NCOA6 is enriched in HF changes and has been suggested to have been under positive selection on the modern human lineage.
“This putative transcription factor is enriched in HF changes and has been suggested to have been under positive selection on the modern human lineage33,122.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [122]
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“In addition, inferences from the signature of selective sweeps will only be possible for very recent speciation events because the genomic footprint of selection is rapidly eroded by mutation and recombination (Racimo et al., 2014).”
<i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution
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- Authors
- Racimo, F., Kuhlwilm, M., & Slatkin, M.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- University of California, Berkeley (US)
- Corresponding author
- Racimo, Fernando
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-28
- Volume
- 31
- Issue
- 12
- Pages
- 3344-3358
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- PMC
- PMC4245817
- OpenAlex
- W2123249494
- Cited by
- 30
- References
- 54
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Biology and Evolution (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM040282, R01‑GM40282)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- approximate Bayesian computation, Denisovan introgression, haplotype diversity, splice site selection, modern human genomes, 1000 Genomes Project
- MeSH terms
- Animals, Bayes Theorem, Humans, Models, Genetic, Selection, Genetic, Genome, Human, Evolution, Molecular, Polymorphism, Single Nucleotide, Neanderthals
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