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Cited by 131Evolution and Genetic DynamicsGenetic Associations and EpidemiologyForensic and Genetic Research

The distribution of deleterious genetic variation in human populations

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Lohmueller, Kirk E·2014·Current Opinion in Genetics & Development
DOI 10.1016/j.gde.2014.09.005

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Abstract

Population genetic studies suggest that most amino-acid changing mutations are deleterious. Such mutations are of tremendous interest in human population genetics as they are important for the evolutionary process and may contribute risk to common disease. Genomic studies over the past 5 years have documented differences across populations in the number of heterozygous deleterious genotypes, number of homozygous derived deleterious genotypes, number of deleterious segregating sites and proportion of sites that are potentially deleterious. These differences have been attributed to population history affecting the ability of natural selection to remove deleterious variants from the population. However, recent studies have suggested that the genetic load is the same across populations and that the efficacy of natural selection has not differed across human populations. Here I show that these observations are not incompatible with each other and that the apparent differences are due to examining different features of the genetic data and differing definitions of terms.

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  • Some researchers have argued for a greater level of deleterious variation in non-Africans rather than in Africans, a pattern opposite to what might be expected given the direction of health disparities.

    “indeed, some researchers have argued for a greater level of deleterious variation in non-Africans rather than in Africans [50, 52], a pattern opposite to what might be expected given the direction of health disparities.”

    From Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences (2019) · cites this paper as [50]

    The 'Efficacy of Natural Selection' section reports a higher proportion of nonsynonymous variants in non-Africans, and Table 1 shows more homozygous derived genotypes in non-Africans. But Table 1 also shows more nonsynonymous variants in Africans and approximately equal numbers of derived alleles per individual, so the paper does not establish a generally greater level of deleterious variation in non-Africans. The passages do not address the claimed contrast with health disparities. (LLM, conf=0.86)

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  • A related computation of the overall influence of natural selection in human history, relying on measures of selection against deleterious variants rather than directional selection of favorable variants, does not suggest strong systematic differences in the magnitude of selection among different continental population groups.

    “However, a related computation of the overall influence of natural selection in human history, relying on measures of selection against deleterious variants rather than directional selection of favorable variants, does not suggest strong systematic differences in the magnitude of selection among different continental population groups [50–52]”

    From Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences (2019) · cites this paper as [50]

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Cites

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Research works printed but not linked: 27

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Authors
Lohmueller, K. E.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Lohmueller, Kirk E
ORCID
Lohmueller, Kirk E
Venue
Current Opinion in Genetics & Development
Publisher
Elsevier BV
Published
2014-12
Volume
29
Pages
139-146
ISSN
0959-437X (ISSN-L)
DOI
10.1016/j.gde.2014.09.005
OpenAlex
W2102495099
Cited by
131
References
3
Citations by year
2026: 1 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 12 · 2020: 7 · 2019: 11 · 2018: 18 · 2017: 12 · 2016: 22 · 2015: 12 · 2014: 2
FWCI
2.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Genetics & Development (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Searle Scholars Fellowship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
human population genetics, genetic load, natural selection, demographic history, selection efficacy, disease risk
MeSH terms
Gene Frequency, Genetics, Population, Genotype, Humans, Models, Genetic, Selection, Genetic, Genetic Variation, Genome, Human, Polymorphism, Single Nucleotide, Genetic Load

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