The evolutionary history of genes involved in spoken and written language: beyond FOXP2
Open accessAbstract
Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed. Herein we analyzed the evolution of ten genes involved in DD and LI. Results show that the evolutionary history of LI genes for mammals and aves was comparable in vocal-learner species and non-learners. For the human lineage, several sites showing evidence of positive selection were identified in KIAA0319 and were already present in Neanderthals and Denisovans, suggesting that any phenotypic change they entailed was shared with archaic hominins. Conversely, in FOXP2, ROBO1, ROBO2, and CNTNAP2 non-coding changes rose to high frequency after the separation from archaic hominins. These variants are promising candidates for association studies in LI and DD.
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The Slit/Robo pathway has been proposed to be involved in vocal learning.
“the proposed involvement of this pathway in vocal learning [104, 105]”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [105]
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Research works printed but not linked: 1
- Mattingly I. G. Reading, the linguistic process and linguistic awareness. In Language by ear and by eyes: the relationships between speech and reading (ed. Kavanagh J. F., Mattingly I. G.) 133– 147 (Cambridge, MA: MIT Press, 1972).
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Sorted by citations
Empirical approaches to the study of language evolution
Fitch, W. T. (2017) · Psychonomic Bulletin & Review · doi:10.3758/s13423-017-1236-5 · Cited by 259 · see citing works
Neanderthal language revisited: not only us
Dediu, D., & Levinson, S. C. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.01.001 · Cited by 218 · see citing works
Self-domestication in Homo sapiens: Insights from comparative genomics
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185306 · Cited by 174 · see citing works
Adani, S., & Cepanec, M. (2019) · Croatian Medical Journal · doi:10.3325/cmj.2019.60.141 · Cited by 150 · see citing works
Discovery of 42 genome-wide significant loci associated with dyslexia
Doust, C., Fontanillas, P., Eising, E., Gordon, S. D., Wang, Z., Alagöz, G., Molz, B., Aslibekyan, S. W., Auton, A., Babalola, E., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01192-y · Cited by 147 · see citing works
Why only us: Recent questions and answers
Berwick, R. C., & Chomsky, N. (2017) · Journal of Neurolinguistics · doi:10.1016/j.jneuroling.2016.12.002 · Cited by 102 · see citing works
The evolution of FOXP2 in the light of admixture
Kuhlwilm, M. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.04.006 · Cited by 56 · see citing works
The Molecular Basis of Human Brain Evolution
Enard, W. (2016) · Current Biology · doi:10.1016/j.cub.2016.09.030 · Cited by 55 · see citing works
Evolution of language: Lessons from the genome
Fisher, S. E. (2017) · Psychonomic Bulletin & Review · doi:10.3758/s13423-016-1112-8 · Cited by 53 · see citing works
The FOXP2-Driven Network in Developmental Disorders and Neurodegeneration
Oswald, F., Klöble, P., Ruland, A., Rosenkranz, D., Hinz, B., Butter, F., Ramljak, S., Zechner, U., & Herlyn, H. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00212 · Cited by 48 · see citing works
Klein, R. G. (2016) · Journal of Neurolinguistics · doi:10.1016/j.jneuroling.2016.11.004 · Cited by 45 · see citing works
Mendoza, E., & Scharff, C. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00112 · Cited by 44 · see citing works
Williams Syndrome, Human Self-Domestication, and Language Evolution
Niego, A., & Benítez‐Burraco, A. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00521 · Cited by 35 · see citing works
García-Pérez, R., Esteller-Cucala, P., Mas, G., Lobon, I., Carlo, V. D., Riera, M., Kuhlwilm, M., Navarro, A., Blancher, A., Croce, L. D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23397-1 · Cited by 33 · see citing works
The genomic landscape of language: Insights into evolution
Mountford, H. S., & Newbury, D. F. (2017) · Journal of Language Evolution · doi:10.1093/jole/lzx019 · Cited by 35 · see citing works
Evolution of regulatory signatures in primate cortical neurons at cell-type resolution
Kozlenkov, A., Vermunt, M. W., Apontes, P., Li, J., Hao, K., Sherwood, C. C., Hof, P. R., Ely, J. J., Wegner, M., Mukamel, E. A., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011884117 · Cited by 30 · see citing works
What aDNA can (and cannot) tell us about the emergence of language and speech
DeSalle, R., & Tattersall, I. (2017) · Journal of Language Evolution · doi:10.1093/jole/lzx018 · Cited by 29 · see citing works
Music-performance regulates microRNAs in professional musicians
Nair, P. S., Kuusi, T., Ahvenainen, M., Philips, A. K., & Järvelä, I. E. (2019) · PeerJ · doi:10.7717/peerj.6660 · Cited by 27 · see citing works
Shriberg, L. D., Strand, E. A., Fourakis, M. S., Jakielski, K. J., Hall, S. D., Karlsson, H. B., Mabie, H. L., McSweeny, J. L., Tilkens, C. M., & Wilson, D. L. (2017) · Journal of Speech Language and Hearing Research · doi:10.1044/2016_jslhr-s-15-0298 · Cited by 29 · see citing works
Mozzi, A., Guerini, F. R., Forni, D., Costa, A. S., Nemni, R., Baglio, F., Cabinio, M., Riva, S., Pontremoli, C., Clerici, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10245-w · Cited by 28 · see citing works
Self-citationLópez, M. E., Cádiz, M. I., Rondeau, E. B., Koop, B. F., & Yañez, J. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-86154-w · Cited by 27 · see citing works
George-Hyslop, F. S., Kivisild, T., & Livesey, F. J. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1017144 · Cited by 28 · see citing works
From melody to words: The role of sex hormones in early language development
Wermke, K., Quast, A., & Hesse, V. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.03.008 · Cited by 23 · see citing works
Grammaticalization and language evolution: Focusing the debate
Benítez‐Burraco, A. (2017) · Language Sciences · doi:10.1016/j.langsci.2017.03.003 · Cited by 21 · see citing works
Lei, H., Yan, Z., Sun, X., Zhang, Y., Wang, J., Ma, C., Xu, Q., Wang, R., Jarvis, E. D., & Sun, Z. (2017) · Brain and Language · doi:10.1016/j.bandl.2017.06.007 · Cited by 18 · see citing works
Did Human Culture Emerge in a Cultural Evolutionary Transition in Individuality?
Davison, D., Andersson, C., Michod, R., & Kuhn, S. (2021) · Biological Theory · doi:10.1007/s13752-021-00382-x · Cited by 17 · see citing works
Trigila, A. P., Pisciottano, F., & Franchini, L. F. (2021) · BMC Biology · doi:10.1186/s12915-021-01170-6 · Cited by 13 · see citing works
Chong, S. L., Tan, J. L., & Ngeow, Y. F. (2022) · BMC Genomics · doi:10.1186/s12864-022-08941-7 · Cited by 11 · see citing works
Araki, T., Hirata, M., Yanagisawa, T., Sugata, H., Onishi, M., Watanabe, Y., Ogata, S., Honda, C., Hayakawa, K., Yorifuji, S., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.05.066 · Cited by 11 · see citing works
Paul, R. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64148-9.00002-8 · Cited by 11 · see citing works
Genetic signatures of socio-communicative abilities in primates
Staes, N., Bradley, B. J., Hopkins, W. D., & Sherwood, C. C. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.11.013 · Cited by 11 · see citing works
Comparative genomics of two Empidonax flycatchers reveal candidate genes for bird song production
García, N. C., Campagna, L., Rush, A. C., Bowie, R. C. K., & Lovette, I. J. (2023) · Evolution · doi:10.1093/evolut/qpad096 · Cited by 9 · see citing works
Grogan, K. E., & Perry, G. H. (2020) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21825 · Cited by 9 · see citing works
Language as a modulator to cognitive and neurological systems
Cui, G. W., Ren, Y., & Zhou, X. (2025) · Acta Psychologica · doi:10.1016/j.actpsy.2025.104803 · Cited by 8 · see citing works
The Neanderthal brain: Biological and cognitive evolution
Macciardi, F. M., & Martini, F. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821428-2.00008-1 · Cited by 8 · see citing works
Cultural Genomics: Promises and Challenges
Chen, C., & Moyzis, R. K. (2018) · Journal of Cross-Cultural Psychology · doi:10.1177/0022022117736526 · Cited by 8 · see citing works
Genetics of human brain evolution
Vallender, E. J. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.01.003 · Cited by 5 · see citing works
Were Neanderthals Rational? A Stoic Approach
Whiting, K., Konstantakos, L., Sadler, G. B., & Gill, C. (2018) · Humanities · doi:10.3390/h7020039 · Cited by 5 · see citing works
Exploring the Psychological basis for Transitions in the Archaeological Record
Gabora, L. M., & Smith, C. M. (2019) · Routledge eBooks · doi:10.4324/9780429488818-12 · Cited by 4 · see citing works
What Would Lenneberg Think? Biolinguistics in the Third Millennium
Fitch, W. T. (2017) · Biolinguistics · doi:10.5964/bioling.9109 · Cited by 3 · see citing works
Early considerations of genetics in aphasia rehabilitation: a narrative review
Harnish, S. M., Diedrichs, V. A., & Bartlett, C. W. (2022) · Aphasiology · doi:10.1080/02687038.2022.2043234 · Cited by 3 · see citing works
Insights From Language‐Trained Apes: Brain Network Plasticity and Communication
Erbaba, B., Sinha, M., Guevara, E. E., Hecht, E. E., Hopkins, W. D., & Sherwood, C. C. (2025) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.70018 · Cited by 2 · see citing works
Specific Language Impairment Genes, Variants and Possible Gene-based Interventions
Eldesouki, R. E. (2021) · Suez Canal University Medical Journal · doi:10.21608/scumj.2021.155491 · Cited by 2 · see citing works
Do Genes Associated with Dyslexia of Chinese Characters Evolve Neutrally?
Nishiyama, K. V., Satta, Y., & Gojobori, J. (2020) · Genes · doi:10.3390/genes11060658 · Cited by 2 · see citing works
Flores-Carrasco, S. V., Figueroa-Barra, A. I., Palma, M. B. L., Roco-Videla, Á., Caviedes-Olmos, M., Pérez-Jiménez, S., & Aguilera-Eguía, R. A. (2024) · Data & Metadata · doi:10.56294/dm2024439 · Cited by 1 · see citing works
Nature or Nurture – Will Epigenomics Solve the Dilemma?
Płonka, B. K. (2016) · Studia Humana · doi:10.1515/sh-2016-0007 · Cited by 1 · see citing works
Xia, W., & Zhang, Z. (2017) · International Journal of Learning and Teaching · doi:10.18178/ijlt.3.4.259-263 · Cited by 1 · see citing works
The Evolution of Language and Speech
Benítez‐Burraco, A., & Dediu, D. (2021) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780198813781.013.29 · Cited by 1 · see citing works
AI + political economics in healthcare
Monlezun, D. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18906-7.00002-7 · Cited by 1 · see citing works
Li, X., Zhu, K., & Zhen, Y. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae614 · Cited by 1 · see citing works
Juan, D., García-Pérez, R., Esteller-Cucala, P., Martín, G. M., Lobón, I., Carlo, V. D., Riera, M., Kuhlwilm, M., Navarro, A., Blancher, A., et al. (2020) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · Cited by 1 · see citing works
On the Interaction of Information and Matter: The Case Study about the Language and BrainPreprint
Chen, L.-J., Liu, Y., Chen, J.-W., Li, X.-M., & Di, Z. (2018) · Preprints.org · doi:10.20944/preprints201812.0365.v1
Epigenetics and the Evolution of Human Social Cognition
Ragsdale, G., & Foley, R. (2018) · Interdisciplinary evolution research · doi:10.1007/978-3-319-93776-2_11
Ma, J. (2019) · International Journal of Language and Linguistics · doi:10.11648/j.ijll.20190702.14
García-Pérez, R., Esteller-Cucala, P., Mas, G., Lobon, I., Carlo, V. D., Riera, M., Kuhlwilm, M., Navarro, A., Blancher, A., Croce, L. D., et al. (2019) · bioRxiv · doi:10.1101/2019.12.18.872531 · Cited by 1 · see citing works
Genomes of extinct hominins and human reproductive evolution
Sengupta, P., Dutta, S., & Chhikara, B. S. (2023) · EXCLI journal · doi:10.17179/excli2023-5991
Martens, B. V. D. V. (2023) · Synthesis lectures on information concepts, retrieval, and services · doi:10.1007/978-3-031-32530-4_3
Pichkar, Y., & Creanza, N. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15750-9.00030-6
Evolving cultures: Shared intentionality and the evolution of symbolism
van Mazijk, C. (2022) · Internationales Jahrbuch für Philosophische Anthropologie · doi:10.1515/jbpa-2022-0003
Auer, M., Miller, P. B., Smith, H. E., & Toomey, J. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009446013.002
Toomey, J. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009446013.004
van der Hulst, H. (2025) · doi:10.1017/9781009346313.013
Language Evolution and Genetics
Benítez‐Burraco, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95504-1.01178-9
Chong, S. L., Tan, J. L., & Ngeow, Y. F. (2022) · Figshare · doi:10.6084/m9.figshare.21366071
Natural selection and language genes in humans
DeSalle, R., Lepski, G. A., Arévalo, A. L., Bobo, D., LaVergne, N., Miyagawa, S., & Tattersall, I. (2026) · Scientific Reports · doi:10.1038/s41598-026-39032-2
FOXP Transcription Factors in Thyroid Cancer: From Molecular Expression to Clinical Significance
Vasiljević, T., Kokanov, N., & Kožik, B. (2026) · Biomedicines · doi:10.3390/biomedicines14061222
- Authors
- Mozzi, A., Forni, D., Clerici, M., Pozzoli, U., Mascheretti, S., Guerini, F. R., Riva, S., Bresolin, N., Cagliani, R., & Sironi, M.
- Affiliations
- IRCCS Eugenio Medea (IT)
- University of Milan (IT)
- Don Carlo Gnocchi Foundation (IT)
- Corresponding author
- Mozzi, Alessandra
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-02-25
- Volume
- 6
- Issue
- 1
- Pages
- 22157-22157
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4766443
- OpenAlex
- W2279694521
- Cited by
- 67
- References
- 96
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 14 · 2016: 5
- FWCI
- 113.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
- Topics
- Social Sciences › Cultural Studies › Language and cultural evolution
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
- Keywords
- language evolution, spoken language, written language, language impairment, developmental dyslexia, FOXP2, KIAA0319, ROBO1, Robo2, CNTNAP2, positive selection, vocal learning, Neanderthals, Denisovans, archaic humans, non-coding variants, comparative genomics
- MeSH terms
- Roundabout Proteins, Animals, Humans, Language Development Disorders, Membrane Proteins, Nerve Tissue Proteins, Receptors, Immunologic, Selection, Genetic, Sequence Alignment, Evolution, Molecular, Forkhead Transcription Factors
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.
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