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Cited by 174Pleistocene-Era Hominins and ArchaeologyForensic and Genetic ResearchLanguage and cultural evolution

Self-domestication in Homo sapiens: Insights from comparative genomics

Open access
Theofanopoulou, Constantina, Gastaldon, Simone, O’Rourke, Thomas, Samuels, Bridget D., Messner, Angela, Martins, Pedro Tiago, Delogu, Francesco, Alamri, Saleh +1 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0185306PMC PMC5646786

Published version of a preprint

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Abstract

This study identifies and analyzes statistically significant overlaps between selective sweep screens in anatomically modern humans and several domesticated species. The results obtained suggest that (paleo-)genomic data can be exploited to complement the fossil record and support the idea of self-domestication in Homo sapiens, a process that likely intensified as our species populated its niche. Our analysis lends support to attempts to capture the "domestication syndrome" in terms of alterations to certain signaling pathways and cell lineages, such as the neural crest.

AI snapshot

Written from the paper’s full text.

TL;DR

This study compares genes under positive selection in anatomically modern humans (AMH) with those in domesticated species and finds a statistically significant overlap, supporting the self-domestication hypothesis for *Homo sapiens*. The overlapping genes implicate neural crest–related, ERK/MAPK, and glutamate-receptor pathways.

Key findings

  • The AMH positively selected gene pool contained 742 genes and the domesticate pool contained 691 genes; their intersection was 41 genes, which was statistically significant by hypergeometric test (p < 0.01) and by Monte Carlo simulation (p = 0.0033; 0.33% of 1,000,000 trials had intersections ≥ 41).
  • Individual overlaps were significant for dog (v = 15, p = 0.0293) and cattle (v = 9, p = 0.0028), but not for cat (v = 15, p = 0.1454) or horse (v = 7, p = 0.122); the domesticate pool overlap was v = 41, p = 0.0034.
  • Great ape comparisons showed non-significant overlaps: chimpanzee v = 16, orangutan v = 20, gorilla v = 12, with Monte Carlo intersections occurring in 40.11%, 32%, and 82.89% of trials, respectively; wolf and wisent also showed no significant convergence with AMH.
  • Five genes showed signals of positive selection in AMH and multiple domesticated species: RNPC3, FAM172A, PLAC8L1, GRIK3, and BRAF; all 41 overlapping genes were found in syntenic blocks across the species studied.

Methods

  • The authors constructed an AMH positively selected gene list (742 genes) from published comparisons with Neanderthals/Denisovans and compared it with a domesticate positively selected gene list (691 genes) from dog, cat, horse, and taurine cattle.
  • They used a hypergeometric intersection test in R with the `hint` package, assuming n = 19,500 average protein-coding genes, and confirmed results with a Matlab Monte Carlo simulation of 1,000,000 random draws without replacement.
  • They performed synteny analysis using NCBI and Ensembl, and functional/pathway analyses using PubMed, GeneCards, UniProt, String, BioGRID, and Ingenuity Pathway Analysis; control comparisons used great apes, Eurasian wolf, and wisent.

Limitations

  • The paper states that it relied on genomic data reflecting the current state of the art for each species, that gene lists came from different analytical tools, that no two studies completely agree even within AMH, and that important genes may have been missed due to database gaps.
  • The paper states that experimental validation is still needed to determine whether the discovered overlaps are associated with mutations that led to similar functional effects across species, and that a stricter convergence criterion (e.g., identical amino acid substitutions) could have been used but was not.
  • The text makes evident that no comprehensive selective sweep analysis exists for Neanderthals, that archaic-specific SNC data were modest at the time, and that rabbit and bonobo gene lists were too small to draw firm conclusions.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0185306

Cites

156 of 156 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 117 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Statistically significant overlaps exist between selective sweep screens in anatomically modern humans and several domesticated species.

    “This study identifies and analyzes statistically significant overlaps between selective sweep screens in anatomically modern humans and several domesticated species.”
    Quote in the paperSubstantial claim
  • Findingnone given

    RNPC3 shows evidence of positive selection in the dog, cat, and AMH.

    “RNPC3 shows evidence of positive selection in the dog, cat, and AMH.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Overlaps between domesticates and several Great Apes (chimpanzee, orangutan, gorilla) were modest and statistically insignificant.

    “This situation contrasted with the modest (statistically insignificant) overlaps between the domesticates and several Great Apes for which selective sweep screens were available: chimpanzee (Pan t. troglodytes), orangutan (Pongo abelii), and gorilla (G. g. gorilla) (see S4 Table).”
    Quote in the paperSubstantial claim
  • Findingown data

    A hypergeometric intersection test showed a significant overlap between genes under selection in the dog and in cattle (p < 0.01).

    “Intersections between domesticates (15 genes in total, see S1 Table) were tested, with a hypergeometric intersection test showing a significant overlap between genes under selection in the dog and in cattle (p < 0.01).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Five genes were found to be associated with signals of positive selection in AMH and multiple domesticated species: RNPC3, FAM172A, PLAC8L1, GRIK3 and BRAF.

    “Five genes were found to be associated with signals of positive selection in AMH and multiple domesticated species (see S3 Table): RNPC3, FAM172A, PLAC8L1, GRIK3 and BRAF.”
    Quote in the paperSubstantial claim
  • May combine two claims. 40
  • Classified as probably not a substantial claim. 26
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Tests between AMH and each domesticate showed significant overlaps with the dog (v = 15, p < 0.05) and with cattle (v = 9, p < 0.01).

    “Furthermore, tests between AMH and each domesticate showed significant overlaps with the dog (v = 15, p < 0.05) and with cattle (v = 9, p < 0.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The intersection of the domesticate and AMH gene lists was 41 genes, representing all genes associated with loci under positive selection both in AMH and in one or more domesticates.

    “The intersection of these lists was found to be the 41 genes shown in Table 1, which represent all of the genes associated with loci under positive selection both in AMH and in one or more domesticates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A significant intersection was found with the data from Prüfer et al. [44] (p < 0.05) and with the combined data from Prüfer et al. [44] and Racimo [48] (p < 0.05).

    “A significant intersection was found with the data from Prüfer et al. [44] (p < 0.05) and with the combined data from Prüfer et al. [44] and Racimo [48] (p < 0.05).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] K Prüfer, 2014, The complete genome sequence of a Neanderthal from the Altai Mountains, Nature source

      Not checked in the free run.

    • cites [48] F Racimo, 2016, Testing for ancient selection using cross-population allele frequency differentiation, Genetics source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The pool of domesticates chosen yielded a total of 691 genes, and the total AMH pool was 742 genes.

    “The pool of domesticates chosen yielded a total of 691 genes, and the total AMH pool, 742 genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither wisent nor wolf populations showed any significant convergence of genes under selection with AMH.

    “Neither wisent nor wolf populations showed any significant convergence of genes under selection with AMH (see S5 Table).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NRG4 shows evidence of selection in cattle, and NRG3 in AMH.

    “NRG4 shows evidence of selection in cattle, and NRG3, in AMH.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    CACNA1D is one of several axon-guidance molecules identified in the study.

    “This gene is one of several axon-guidance molecules we identified in our study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    NOVA1 and RASA1 show AMH-specific amino-acid substitutions and are involved in neuronal development.

    “several genes showing AMH-specific amino-acid substitutions, such as NOVA1 and RASA1, both involved in neuronal development”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DCC shows signatures of positive selection in both the horse and the cat, and interacts strongly with DSCAM, another axon-guidance and neural crest-related gene, selected for in cattle.

    “DCC (DCC Netrin 1 receptor), an axon-guidance mediator and neural crest-related gene, which shows signatures of positive selection in both the horse and the cat, interacts strongly with DSCAM (Down Syndrome cell adhesion molecule), another axon-guidance and neural crest-related gene, selected for in cattle.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    COL11A1 is under selection in the dog and AMH.

    “including COL11A1, under selection in the dog and AMH.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We identified common themes pertaining to neuronal development, synaptic plasticity, and enhanced learning.

    “Apart from neural crest-related genes and pathways, we identified common themes pertaining to neuronal development, synaptic plasticity, and enhanced learning.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A significant intersection was found with the data in [44] (a = 691, b = 108, v = 9; p < 0.05) and with the combined data from [44] and [48] (a = 691, b = 419, v = 24, p < 0.05).

    “A significant intersection was found with the data in [44] (a = 691, b = 108, v = 9; p < 0.05) and with the combined data from [44] and [48] (a = 691, b = 419, v = 24, p < 0.05).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] K Prüfer, 2014, The complete genome sequence of a Neanderthal from the Altai Mountains, Nature source

      Not checked in the free run.

    • cites [48] F Racimo, 2016, Testing for ancient selection using cross-population allele frequency differentiation, Genetics source

      Not checked in the free run.

    • The authors state this as an assumption: The average number of protein-coding genes for all species considered is 19,500.

  • The quote only partly states this claim.

    Findingown data

    Monte Carlo simulation showed that 0.33% of 1,000,000 trials had intersections ≥41.

    “The results revealed that 0.33% of trials had intersections of this size.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The average number of protein-coding genes for all species considered is 19,500.

  • May combine two claims.

    Interpretationown data

    Anatomically modern humans and domesticated species share evolutionary trajectories and convergent signatures of selection.

    “We argue that such characterizations are accurate, not merely as analogies, but in identifying shared evolutionary trajectories, with accompanying convergent signatures of selection, in AMH and domesticated species.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Domesticated species display a range of anatomical and behavioral phenotypes that set them apart from their wild counterparts, including depigmentation, floppy reduced ears, shorter muzzles, curly tails, smaller teeth, smaller cranial capacities, paedomorphosis, neotenous behavior, reduction of sexual dimorphism, docility, and more frequent estrous cycles.

    “Domesticated species display a range of anatomical and behavioral phenotypes that set them apart from their wild counterparts: depigmentation; floppy, reduced ears; shorter muzzles; curly tails; smaller teeth; smaller cranial capacities (and concomitant brain size reduction); paedomorphosis; neotenous (juvenile) behavior; reduction of sexual dimorphism (feminization); docility; and more frequent e”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] MR Sánchez-Villagra, 2016, The taming of the neural crest: a developmental perspective on the origins of morphological covariation in domesticated mammals, Open Science

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High-quality genomes are available for Neanderthals and Denisovans, allowing genomic comparison with anatomically modern humans, as well as genomes of several domesticated species that can be compared with their wild counterparts.

    “Crucially, we now have high-quality genomes for our closest extinct relatives, the Neanderthals and Denisovans, allowing for genomic comparison with AMH [42], as well as genomes of several domesticated species, which can be compared with their wild counterparts [43].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [42] B Llamas, 2017, Human evolution: a tale from ancient genomes, Phil Trans R Soc B source

      Not checked in the free run.

    • cites [43] L Orlando, 2016, Ancient DNA and the Study of Animal Domestication, Annual Review of Animal Biosciences

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Reduced reactivity or increased prosocial behaviors are necessary precursors of self-domestication, but not sufficient to describe the full-blown suite of traits associated with the domestication syndrome.

    “Certainly, reduced reactivity or increased prosocial behaviors seem to be necessary precursors of self-domestication, but these are not sufficient to describe the full-blown suite of traits associated with the domestication syndrome.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    The self-domestication hypothesis is a strong contender to account for key aspects of modern human cognition.

    “The self-domestication hypothesis is, then, a strong contender to account for key aspects of modern human cognition.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The anatomically modern human profile is associated with an overall reduction of sexual dimorphism, which is also associated with domestication.

    “This profile is sometimes called ‘feminized’ [21], and is associated with an overall reduction of sexual dimorphism, which is also associated with domestication [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] B Hare, 2012, The self-domestication hypothesis: evolution of bonobo psychology is due to selection against aggression, Animal Behaviour source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NR2F1 plays a role in regulating neural crest specifier genes and has undergone selection in AMH.

    “NR2F1, which plays a role in regulating neural crest specifier genes and has undergone selection in AMH [64, 65]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] A Rada-Iglesias, 2012, Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest, Cell stem cell source

      Not checked in the free run.

    • cites [65] M Simões-Costa, 2015, Establishing neural crest identity: a gene regulatory recipe, Development source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BRAF is upstream of ERK2, which plays a critical role in neural crest development and regulates neuronal gene expression in both the neocortex and hippocampus.

    “BRAF is upstream of ERK2, which plays a critical role in neural crest development [71] and regulates neuronal gene expression in both the neocortex and hippocampus [69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [71] J Newbern, 2008, Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development, Proceedings of the National Academy of Sciences source

      Not checked in the free run.

    • cites [69] JD Sweatt, 2001, The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory, Journal of neurochemistry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BRAF is an important member of the ERK/MAPK signaling pathway, which plays a key role in synaptic plasticity, memory, and learning.

    “BRAF, under selection in the cat, horse, and AMH, is an important member of the ERK/MAPK signaling pathway, which has been shown to play a key role in synaptic plasticity, memory, and learning [69]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] JD Sweatt, 2001, The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory, Journal of neurochemistry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An autistic patient has been noted as having a microdeletion at chromosome 5q32, a location which includes PLAC8L1.

    “An autistic patient has been noted as having a microdeletion at chromosome 5q32, a location which includes PLAC8L1 [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] SSF Gau, 2012, Identification of two inherited copy number variants in a male with autism supports two-hit and compound heterozygosity models of autism, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Domestication is known to proceed through various routes and is not a uniform affair.

    “As discussed in the Introduction, domestication is known to proceed through various routes, and is thus not a uniform affair.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    NR2F2 is involved in regulating embryonic stem cell differentiation and implicated in neural crest development, and has been under selection in the domesticated fox.

    “The functionally related nuclear receptor NR2F2 is involved in regulating embryonic stem cell differentiation [66] and implicated in neural crest development, and has been under selection in the domesticated fox [67].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [66] A Rosa, 2011, A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation, The EMBO journal source

      Not checked in the free run.

    • cites [67] JL Johnson, 2015, Genotyping-by-sequencing (GBS) detects genetic structure and confirms behavioral QTL in tame and aggressive foxes (Vulpes vulpes), PloS one source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BRAF is implicated in Noonan, Leopard, and Cardiofaciocutaneous syndromes, with typical symptoms including prominent forehead, bitemporal narrowing, hypertelorism, short stature, and other skeletal, cardiac, and craniofacial anomalies, frequently accompanied by moderate to severe mental retardation.

    “BRAF is implicated in Noonan, Leopard, and Cardiofaciocutaneous syndromes, typical symptoms of which include prominent forehead, bitemporal narrowing, hypertelorism, and short stature, among other skeletal, cardiac, and craniofacial anomalies, frequently accompanied by moderate to severe mental retardation [72, 73].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [72] A Keyte, 2012, The neural crest in cardiac congenital anomalies, Differentiation source

      Not checked in the free run.

    • cites [73] A Sarkozy, 2009, Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum, Human mutation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hirschsprung disease affects the neural crest, which is associated with domestication syndrome.

    “This disease is very relevant in the context of domestication, as it affects the neural crest, associated with domestication syndrome [17, 38].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] AS Wilkins, 2014, The “domestication syndrome” in mammals: a unified explanation based on neural crest cell behavior and genetics, Genetics source

      Not checked in the free run.

    • cites [38] A Benítez-Burraco, 2016, Globularization and domestication, Topoi

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERBB4 shows evidence of selection in humans, is part of the ERK/MAPK pathway, and negatively regulates ERK via upstream phosphorylation of Raf-1.

    “the neuregulin (NRG) receptor ERBB4, which shows evidence of selection in humans, is part of the ERK/MAPK pathway and negatively regulates ERK via upstream phosphorylation of Raf-1 [76].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] M Hatakeyama, 2003, A computational model on the modulation of mitogen-activated protein kinase (MAPK) and Akt pathways in heregulin-induced ErbB signalling, Biochemical Journal source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CBL mutations give rise to a Noonan syndrome-like disorder.

    “when mutated, has been shown to give rise to a Noonan syndrome-like disorder [75].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] S Martinelli, 2010, Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype, The American Journal of Human Genetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERBB4 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.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [44] K Prüfer, 2014, The complete genome sequence of a Neanderthal from the Altai Mountains, Nature source

      Not checked in the free run.

    • cites [46] S Peyrégne, 2016, Detecting ancient positive selection in humans using extended lineage sorting, bioRxiv

      Not checked in the free run.

    • cites [78] F Racimo, 2014, A test for ancient selective sweeps and an application to candidate sites in modern humans, Molecular biology and evolution source

      Not checked in the free run.

    • cites [38] A Benítez-Burraco, 2016, Globularization and domestication, Topoi

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SOS1, under selection in domesticated foxes, affects MAPK signaling, bringing about Noonan phenotypes.

    “Upstream of BRAF, SOS1, under selection in domesticated foxes, affects MAPK signaling, bringing about Noonan phenotypes [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] AE Roberts, 2007, Germline gain-of-function mutations in SOS1 cause Noonan syndrome, Nature genetics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NRG3 copy number and single nucleotide variants have been associated with Hirschsprung disease.

    “NRG3 copy number and single nucleotide variants have been associated with Hirschsprung disease [79, 80].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [79] CSM Tang, 2012, Genome-wide copy number analysis uncovers a new HSCR gene: <italic>NRG3</italic>, PLoS Genet

      Not checked in the free run.

    • cites [80] J Yang, 2013, Exome sequencing identified <italic>NRG3</italic> as a novel susceptible gene of Hirschsprung’s disease in a Chinese population, Mol Neurobiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLC9A6 encodes sodium/hydrogen exchanger protein 6, which is part of a network related to the plasticity of glutaminergic neurons.

    “This gene encodes sodium/hydrogen exchanger protein 6, which is part of a network related to the plasticity of glutaminergic neurons [86].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] GD Gilfillan, 2008, SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome, The American Journal of Human Genetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DLGAP1 interacts with the glutamate receptor GRIK2, also implicated in obsessive-compulsive disorders.

    “DLGAP1 interacts with the glutamate receptor GRIK2, also implicated in obsessive-compulsive disorders [101].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] M Mattheisen, 2015, Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS, Molecular psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polymorphisms in GRIK3 and GRID1 have been implicated in schizophrenia.

    “Polymorphisms in GRIK3 and GRID1 have been implicated in schizophrenia [94, 95]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [94] S Begni, 2002, Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala polymorphism and schizophrenia, Molecular psychiatry source

      Not checked in the free run.

    • cites [95] SZ Guo, 2007, A case-control association study between the GRID1 gene and schizophrenia in the Chinese Northern Han population, Schizophrenia research

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several association studies have identified DCC as a promising candidate for schizophrenia.

    “several association studies have identified DCC as a promising candidate for schizophrenia [109]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] A Grant, 2012, Association between schizophrenia and genetic variation in DCC: a case–control study, Schizophrenia research source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Slit/Robo pathway has been proposed to be involved in vocal learning.

    “the proposed involvement of this pathway in vocal learning [104, 105]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [104] R Wang, 2015, Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners, Journal of Comparative Neurology source

      Not checked in the free run.

    • cites [105] A Mozzi, 2016, The evolutionary history of genes involved in spoken and written language: beyond FOXP2, Scientific reports source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Genes involved in glutamate metabolism show the greatest population differentiation by whole-genome comparison of dogs and wolves.

    “Previous work by Li et al. [102] already pointed out that genes involved in glutamate metabolism show the greatest population differentiation by whole-genome comparison of dogs and wolves.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Y Li, 2014, Domestication of the dog from the wolf was promoted by enhanced excitatory synaptic plasticity: a hypothesis, Genome biology and evolution source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Phenotypes typical of Christianson syndrome patients include cognitive developmental delays, absence of speech, stereotyped repetitive hand movements, and postnatal microcephaly with a narrow face; the syndrome is frequently characterized by a happy disposition with easily provoked laughter and smiling, an open mouth with excessive drooling, and frequent visual fixation on hands.

    “Phenotypes typical of these patients include cognitive developmental delays, absence of speech, stereotyped repetitive hand movements, and postnatal microcephaly with a narrow face. Christianson syndrome is frequently characterized by a happy disposition with easily provoked laughter and smiling, an open mouth with excessive drooling and frequent visual fixation on hands.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DCC is involved in the organization of dopaminergic circuits within the cortex.

    “DCC is involved in the organization of dopaminergic circuits within the cortex [108]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] C Manitt, 2011, The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry, The Journal of Neuroscience source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An AMH-specific hCONDEL exists in a region upstream of DCC, although it is shared with Neanderthals.

    “an AMH-specific hCONDEL exists in a region upstream of DCC, although it is shared with Neanderthals [110]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] CY McLean, 2011, Human-specific loss of regulatory DNA and the evolution of human-specific traits, Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CACNA1D is a neural cell adhesion molecule that contributes to cell migration via activation of MAPK/ERK signaling.

    “CACNA1D is a neural cell adhesion molecule that contributes to cell migration via activation of MAPK/ERK signaling [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Y Shi, 2012, Neural cell adhesion molecule modulates mesenchymal stromal cell migration via activation of MAPK/ERK signaling, Experimental cell research source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ROBO silences the attractive effect that Netrin 1 has on DCC, allowing SLIT2 to bind to this ligand and enabling axon pathfinding in the developing brain.

    “ROBO silences the attractive effect that Netrin 1 has on DCC, allowing SLIT2 to bind to this ligand and enabling axon pathfinding in the developing brain [106, 107].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [106] E Stein, 2001, Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex, Science source

      Not checked in the free run.

    • cites [107] RE Dickinson, 2010, The SLIT–ROBO pathway: a regulator of cell function with implications for the reproductive system, Reproduction source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An analysis of a domesticated pig genome suggests that the involvement of the ERK pathway in domestication extends beyond the species focused on in this study.

    “an analysis of a domesticated pig (Sus scrofa domesticus) genome [88] suggests that the involvement of ERK pathway in domestication extends beyond the species we focused on in this study.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] M Li, 2014, Whole-genome sequencing of Berkshire (European native pig) provides insights into its origin and domestication, Scientific reports source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CACNA1D is highly expressed in the adrenal glands, and when mutated gives rise to cerebral palsy/motor disorders; it has been linked to auditory processing and is among the positively selected genes in some vocal learners.

    “It is highly expressed in the adrenal glands [90], and, when mutated, gives rise to cerebral palsy/motor disorders [91]. It has been linked to auditory processing [92], and said to be among the positively selected genes in some vocal learners [93].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [90] EA Azizan, 2013, Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension, Nature genetics source

      Not checked in the free run.

    • cites [91] UI Scholl, 2013, Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism, Nature genetics source

      Not checked in the free run.

    • cites [92] SV Satheesh, 2012, Retrocochlear function of the peripheral deafness gene Cacna1d, Human molecular genetics

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DLGAP1 has been implicated in obsessive-compulsive disorders and interacts significantly with Shank proteins, mutations in which have been linked to autism spectrum disorders with impaired social interaction and communication.

    “This gene has been implicated in obsessive-compulsive disorders and interacts significantly with Shank proteins, mutations in which have been linked to autism spectrum disorders with impaired social interaction and communication [98–100].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [98] O Bozdagi, 2010, Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication, Molecular autism source

      Not checked in the free run.

    • cites [99] SE Stewart, 2013, Genome-wide association study of obsessive-compulsive disorder, Molecular psychiatry source

      Not checked in the free run.

    • cites [100] H Won, 2012, Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function, Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Domestication may be best represented as a spectrum or continuum, with a polygenic basis and non-uniform symptomatology.

    “This is consistent with the view that domestication may be best represented as a spectrum or continuum [120], with a polygenic basis and non-uniform symptomatology.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] JD Vigne, 2011, The origins of animal domestication and husbandry: a major change in the history of humanity and the biosphere, Comptes rendus biologies source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Different amino acid changes around the site of an AMH-specific derived protein, ADSL (A429V), can bring about adenylosuccinate lyase deficiency (R426H; D430N), the symptoms of which include developmental delay, autistic-like traits, aggressiveness, and microcephaly.

    “Different amino acid changes around the site of an AMH-specific derived protein, ADSL (A429V), can bring about adenylosuccinate lyase deficiency (R426H; D430N [118]), the symptoms of which include developmental delay, autistic-like traits, aggressiveness, and microcephaly [119].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [118] S Kmoch, 2000, Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients, Human molecular genetics source

      Not checked in the free run.

    • cites [119] A Jurecka, 2015, Adenylosuccinate lyase deficiency, Journal of inherited metabolic disease source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A disruption in neural crest developmental programs might be the source of changes spanning multiple organ systems and morphological structures.

    “A disruption in neural crest developmental programs might be the source of changes spanning multiple organ systems and morphological structures [17]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] AS Wilkins, 2014, The “domestication syndrome” in mammals: a unified explanation based on neural crest cell behavior and genetics, Genetics source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The fact that we find neural crest-related changes in AMH compared to Neanderthals/Denisovans, and that such changes are also found in another species hypothesized to have undergone a self-domestication process, reinforces our hypothesis that self-domestication took place in our species.

    “The fact that we find neural crest-related changes in AMH compared to Neanderthals/Denisovans, and that such changes are also found in another species hypothesized to have undergone a self-domestication process, reinforces our hypothesis that self-domestication took place in our species.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    These results are in line with claims in other studies on domestication, where categories like 'neurological process' frequently stand out strongly in gene ontology category enrichment analyses.

    “These results are in line with claims in other studies on domestication [49, 123–125], where categories like ‘neurological process’ frequently stand out strongly in gene ontology category enrichment analyses.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [49] AH Freedman, 2016, Demographically-based evaluation of genomic regions under selection in domestic dogs, PLoS Genet source

      Not checked in the free run.

    • cites [123] CE Stanley, 2016, Genomic signatures of domestication on neurogenetic genes in Drosophila melanogaster, BMC evolutionary biology source

      Not checked in the free run.

    • cites [124] Gd Wang, 2013, The genomics of selection in dogs and the parallel evolution between dogs and humans, Nature communications source

      Not checked in the free run.

    • cites [125] M Carneiro, 2014, Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication, Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    These categories are often mentioned in studies on selective sweeps in AMH.

    “These categories are often mentioned in studies on selective sweeps in AMH (e.g., [46]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] S Peyrégne, 2016, Detecting ancient positive selection in humans using extended lineage sorting, bioRxiv

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Significant brain gene expression differences exist across domesticates, with the majority of these changes being species-specific.

    “This state of affairs is reflected in significant brain gene expression differences across domesticates, with the majority of these changes being species-specific [121].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] FW Albert, 2012, A comparison of brain gene expression levels in domesticated and wild animals, PLoS Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The lists of genes associated with signals of positive selection are derived from the literature, and were generated using different analytical tools.

    “The lists of genes associated with signals of positive selection are derived from the literature, and were generated using different analytical tools.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The build-up of deleterious alleles could be a byproduct of self-domestication in AMH, too.

    “which, if true, could be a byproduct of self-domestication in AMH, too.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Study design and conductnone given

    It remains to be determined experimentally that the overlaps discovered here are indeed associated with mutations that led to similar functional effects across species.

    “Last, but not least, it remains to be determined experimentally that the overlaps discovered here are indeed associated with mutations that led to similar functional effects across species.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Convergent evolution is often hypothesized to occur in the absence of a very strict notion of convergence; for instance, convergent evolution in the domain of vocal learning is related to non-identical changes in FOXP2 across vocal learners.

    “given that convergent evolution is often hypothesized to occur in the absence of this very strict notion of convergence—for instance, convergent evolution in the domain of vocal learning is related to non-identical changes in FOXP2 across vocal learners [134]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [134] DM Webb, 2005, FoxP2 in song-learning birds and vocal-learning mammals, Journal of Heredity source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Even within a single species (e.g., AMH), no two studies completely agree on a definitive list.

    “even within a single species (e.g., AMH), no two studies completely agree on a definitive list.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Study design and conductreasoning

    We may have missed important genes of interest due to the lack of information on them in the various databases we consulted.

    “In addition, we may have missed important genes of interest due to the lack of information on them in the various databases we consulted.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    In some cases, studies produce lists of very different sizes.

    “Indeed, in some cases, they produce lists of very different sizes.”
    Quote in the paperNot a substantial claim
60 of 60

  • The paper relies on this without support.

    The gene sets reported as under positive selection in the cited studies are accurate and comparable across species.

    “We examined the overlap of gene sets independently claimed to be under positive selection in AMH (when compared with Neanderthal/Denisovan) and several domesticates for which detailed genetic information is available”

  • The authors state this as an assumption.

    The average number of protein-coding genes for all species considered is 19,500.

    “As a model of our data we chose as a simplifying assumption n = 19,500 as the average number of protein-coding genes for all the species taken into consideration.”

  • The paper relies on this without support.

    No comprehensive selective sweep analysis exists for Neanderthals.

    “To the best of our knowledge, no comprehensive selective sweep analysis exists for Neanderthals.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Comparison of humans and other domesticated species has shown an overlap of genes under positive selection that was not present in their wild counterparts.

    “Comparison of humans and other domesticated species (dogs, cats, horses and cattle) has shown an overlap of genes under positive selection that was not present in their wild counterparts.47”

    From Ecological validity of social interaction tests in rats and mice (2019) · cites this paper as [47]

  • Anatomically modern humans and domesticated species have followed convergent evolutionary processes compared to their respective archaic and wild counterparts.

    “Over recent years, genomic, transcriptomic, behavioral, and archaeological evidence has begun to accumulate, indicating that anatomically modern humans and domesticated species have followed convergent evolutionary processes compared to their respective archaic and wild counterparts [8–10].”

    From Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle (2021) · cites this paper as [10]

  • Our observation that genes associated with archaic human regulatory changes show above-chance intersection with Lidia cattle DEGs mirrors findings that genetic changes in anatomically modern humans converge with those of domesticated species (including cattle).

    “Our observation that genes associated with archaic human regulatory changes show above-chance intersection with Lidia cattle DEGs mirrors findings that genetic changes in anatomically modern humans converge with those of domesticated species (including cattle) [9, 10].”

    From Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle (2021) · cites this paper as [10]

  • This pathway is highlighted as having been altered in multiple domestication events (including that of cattle), as well as in modern-human evolution.

    “This pathway is also highlighted as having been altered in multiple domestication events (including that of cattle), as well as in modern-human evolution [10].”

    From Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle (2021) · cites this paper as [10]

  • Anatomically modern humans exhibit a suite of craniofacial and prosocial characteristics reminiscent of traits distinguishing domesticated species from their wild counterparts.

    “Anatomically modern humans (AMHs) exhibit a suite of craniofacial and prosocial characteristics that are reminiscent of traits distinguishing domesticated species from their wild counterparts (1–3).”

    From Dosage analysis of the 7q11.23 Williams region identifies <i>BAZ1B</i> as a major human gene patterning the modern human face and underlying self-domestication (2019) · cites this paper as [1]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • CACNA1D is assigned conflicting molecular identities

    Minor

    The results call CACNA1D a neural cell adhesion molecule, whereas the cited reference [91] explicitly identifies CACNA1D mutations as calcium-channel mutations.

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 2

  1. R Lacruz, 2015, Facial ontogeny in Neanderthals and their ancestors, Nature Communications
  2. AL Pendleton, 2017, Selective sweep analysis using village dogs highlights the pivotal role of the neural crest in dog domestication, bioRxiv, 118794

Cited by

Sorted by citations

Related

Authors
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C.
Affiliations
  • Universitat de Barcelona (ES)
  • University of Padua (IT)
  • University of Southern California (US)
  • Norwegian University of Life Sciences (NO)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
Corresponding author
Boeckx, Cedric
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-10-18
Volume
12
Issue
10
Pages
e0185306
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0185306
PMC
PMC5646786
OpenAlex
W2765578131
Semantic Scholar
4c27b723eaed725450eaef155248e923fb4c3c5e
Cited by
174
References
156
Citations by year
2026: 6 · 2025: 7 · 2024: 13 · 2023: 17 · 2022: 26 · 2021: 33 · 2020: 41 · 2019: 18 · 2018: 8 · 2017: 5
FWCI
79.24
Type
journal article
Language
en
Update notices
correction (2018-05-11)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
  • Generalitat de Catalunya (2014-SGR-200)
  • Spanish Ministry of Economy and Competitiveness (FFI2016-78034-C2- 1-P)
  • Marie Curie International Reintegration Grant from the European Union (PIRG-GA-2009-256413)
  • Fundació Bosch i Gimpera
Topics
  • Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
  • Social Sciences › Cultural Studies › Language and cultural evolution
Keywords
self-domestication, human, domestication syndrome, selective sweeps, comparative genomics, anatomically modern humans, neural crest, signaling pathways, cell lineage, paleogenomics, fossil record
MeSH terms
Domestication, Alleles, Animals, Humans, Selection, Genetic, Species Specificity, Hominidae, Gene Expression Profiling, Genomics, Synteny

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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