Principles for the buffering of genetic variation
Abstract
Most genetic research has used inbred organisms and has not explored the complexity of natural genetic variation present in outbred populations. The translation of genotype to phenotype is complicated by gene interactions observed as epistasis, canalization, robustness, or buffering. Analysis of double mutations in inbred experimental organisms suggests some principles for gene interaction that may apply to natural variation as well. The buffering of variation in one gene is most often due to a small number of other genes that function in the same biochemical process. However, buffering can also result from genes functioning in processes extrinsic to that of the primary gene.
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A large part of phenotype variability across patients with the same ABCD1 genotype may be due to stochasticity.
“Beyond identifiable causes, a large part of phenotype variability across patients with the same ABCD1 genotype may “simply” be due to stochasticity, a factor hitherto considered “noise” by Cartesian researchers.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [133]
Stochasticity rules all living cells through fluctuations in gene expression, molecular interactions, and metabolic fluxes, even systems governed by deterministic laws.
“Actually, stochasticity rules all living cells through fluctuations in gene expression, molecular interactions, and metabolic fluxes, even systems governed by deterministic laws, such as monogenic genetics [131,132,133,134].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [133]
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- Authors
- Hartman, J. L., Garvik, B., & Hartwell, L.
- Affiliations
- Fred Hutch Cancer Center (US)
- Houston Methodist (US)
- Corresponding author
- Hartwell, Lee
- ORCID
- Hartman, John L.
- Venue
- Science
- Published
- 2001-02-09
- Volume
- 291
- Issue
- 5506
- Pages
- 1001-1004
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1975931018
- Cited by
- 808
- References
- 2
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 17 · 2023: 19 · 2022: 17 · 2021: 19 · 2020: 29 · 2019: 32 · 2018: 26 · 2017: 34 · 2016: 24 · 2015: 39 · 2014: 43 · 2013: 35 · 2012: 53
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM17709)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy and History of Science
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- epistasis, canalization, robustness, genetic interactions, double mutations, natural genetic variation, genotype-phenotype correlation, outbred populations
- MeSH terms
- Alleles, Animals, Epistasis, Genetic, Biological Evolution, Genes, Genotype, Humans, Mutation, Phenotype, Genetic Variation, Yeasts, Quantitative Trait, Heritable
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