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The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics
Open accessAbstract
Charles Darwin, while trying to devise a general theory of heredity from the observations of animal and plant breeders, discovered that domesticated mammals possess a distinctive and unusual suite of heritable traits not seen in their wild progenitors. Some of these traits also appear in domesticated birds and fish. The origin of Darwin’s “domestication syndrome” has remained a conundrum for more than 140 years. Most explanations focus on particular traits, while neglecting others, or on the possible selective factors involved in domestication rather than the underlying developmental and genetic causes of these traits. Here, we propose that the domestication syndrome results predominantly from mild neural crest cell deficits during embryonic development. Most of the modified traits, both morphological and physiological, can be readily explained as direct consequences of such deficiencies, while other traits are explicable as indirect consequences. We first show how the hypothesis can account for the multiple, apparently unrelated traits of the syndrome and then explore its genetic dimensions and predictions, reviewing the available genetic evidence. The article concludes with a brief discussion of some genetic and developmental questions raised by the idea, along with specific predictions and experimental tests.
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“This implies that the genetic architecture of domestication is by necessity pleiotropic, with variants in genes affecting neural crest development and distribution causing multiple domestication traits.”
From The neural crest cell hypothesis: no unified explanation for domestication (2021) · cites this paper as Wilkins et al. (2014)
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The hypothesis entails that a reduction in neural crest cell proliferation and migration is a core genetic mechanism of early domestication.”
From The neural crest cell hypothesis: no unified explanation for domestication (2021) · cites this paper as Wilkins et al. (2014)
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The characters affected by Dlx5/6 in the mouse (sociability, vocalization, skull, and brain shape…) overlap those affected in the “domestication syndrome”.”
From DLX5/6 GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Wilkins, et al. 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The authors also suggest that neural crest cell function is polygenic, affected by many genetic variants with individually small effects.”
From The neural crest cell hypothesis: no unified explanation for domestication (2021) · cites this paper as Wilkins et al. (2014)
The cited source says what the claim attributes to it.
In the citing paper
“the neural-crest cell hypothesis of domestication assumes that a process of domestication leads to depigmentation rather than an intensification of pigmentation [40,41].”
From Are dark-eyed dogs favoured by humans? Domestication as a potential driver of iris colour difference between dogs and wolves (2023) · cites this paper as [40]
In the citing paper
“The concept of”
From Ecological validity of social interaction tests in rats and mice (2019) · cites this paper as [48]
In the citing paper
“The process of ‘feminization’ (reduction of androgen levels and rise in estrogen levels [21]) is often associated with reduced reactivity of the hypothalamus-pituitary-adrenal axis [26], a physiological trait thought to be critical for domestication [17, 27].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [17]
In the citing paper
“This disease is very relevant in the context of domestication, as it affects the neural crest, associated with domestication syndrome [17, 38].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [17]
In the citing paper
“we find the overlaps listed in S1 and S2 Tables and the associated functions and pathways discussed in the Results section all the more relevant, especially because they converge to a large extent with what is to be expected from the neural crest-based hypothesis [17] put forth to capture the common mechanistic basis of domestication events.”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [17]
In the citing paper
“A disruption in neural crest developmental programs might be the source of changes spanning multiple organ systems and morphological structures [17]”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [17]
In the citing paper
“Furthermore a biological hypothesis for the production of domestication syndromes (Wilkins et al., 2014) has received important support (Wilkins, 2017; Pendleton et al., 2018), including evidence that genetic variants underlying self-domestication occur in H. sapiens but not in H. neanderthalensis or Denisovans (Theofanopoulou et al., 2017).”
From Hypotheses for the Evolution of Reduced Reactive Aggression in the Context of Human Self-Domestication (2019) · cites this paper as Wilkins et al., 2014
In the citing paper
“(iii) the first formulation of the neurocristopathic hypothesis of domestication, which included BAZ1B among the genes influencing NC development (5);”
From Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [5]
In the citing paper
“Mild NC deficits have been put forth as a unifying explanatory framework for the defining features of the so-called domestication syndrome, with BAZ1B listed among the putative underlying genes because of its previously reported role in the NC of model organisms (5, 10, 11).”
From Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [5]
In the citing paper
“since NC changes have been implicated in the domestication syndrome (5)”
From Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [5]
In the citing paper
“The first problem was tackled by the recent proposition of mild NC deficits as a central and unifying functional layer underlying domestication (5).”
From Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [5]
In the citing paper
“Third, our investigation provides the first experimental evidence for the neurocristopathic hypothesis that had been put forth to explain the domestication syndrome and had pointed to BAZ1B as one of the candidates underlying this syndrome (5).”
From Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [5]
In the citing paper
“the hypofunction of which has been proposed as a key mechanism in the development of tame behaviors in domesticates (Trut et al., 2009;Wilkins et al., 2014).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Wilkins et al., 2014
In the citing paper
“Alterations to the HPA axis are considered to be essential for the emergence of tameness in different (indeed competing) theories of domestication (Wilkins et al., 2014;Belyaev, 1979).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Wilkins et al., 2014
In the citing paper
“The genetic signals from this analysis fall in line with the predictions of the domestication syndrome hypothesis (50), which posits that the morphological and physiological traits modified by mammalian domestication are explained by direct and indirect consequences of mild neural crest cell deficits during embryonic development.”
From Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication (2014) · cites this paper as [50]
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Cites
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Li, M.-H., & Salehian-Dehkordi, H. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-43994-0.00001-0
Metadata
- Authors
- Wilkins, A. S., Wrangham, R. W., & Fitch, W. T.
- Affiliations
- Stellenbosch University (ZA)
- Harvard University (US)
- University of Vienna (AT)
- Corresponding author
- Wilkins, Adam S
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-01
- Volume
- 197
- Issue
- 3
- Pages
- 795-808
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC4096361
- OpenAlex
- W2165155571
- Cited by
- 751
- References
- 114
- Citations by year
- 2026: 35 · 2025: 60 · 2024: 87 · 2023: 113 · 2022: 81 · 2021: 76 · 2020: 77 · 2019: 72 · 2018: 45 · 2017: 45 · 2016: 40 · 2015: 14 · 2014: 4
- FWCI
- 22.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- FP7 Ideas: European Research Council (230604)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Human-Animal Interaction Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Morphological variations and asymmetry
- Keywords
- domestication syndrome, neural crest cells, embryonic development, developmental genetics, heritable traits
- MeSH terms
- Animals, Animals, Domestic, Behavior, Animal, Mammals, Models, Genetic, Neural Crest, Syndrome, Epigenesis, Genetic
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