Axon guidance pathways served as common targets for human speech/language evolution and related disorders
Abstract
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders.
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Genes associated with axon guidance functions, important for refinement of neural circuits including those relevant for speech and language, are found in introgression deserts.
“genes associated with axon guidance functions, which are important for the refinement of neural circuits including those relevant for speech and language, are found in introgression deserts126,127.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [126]
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- Authors
- Lei, H., Yan, Z., Sun, X., Zhang, Y., Wang, J., Ma, C., Xu, Q., Wang, R., Jarvis, E. D., & Sun, Z.
- Affiliations
- Capital Medical University (CN)
- Tsinghua University (CN)
- Capital Institute of Pediatrics (CN)
- Peking University Third Hospital (CN)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lei, Huimeng
- Sun, Zhirong
- ORCID
- Venue
- Brain and Language
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 174
- Pages
- 1-8
- ISSN
- 0093-934X (ISSN-L)
- OpenAlex
- W2724787509
- Cited by
- 18
- References
- 51
- Citations by year
- 2025: 2 · 2024: 3 · 2022: 3 · 2020: 5 · 2019: 4 · 2018: 1
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain and Language (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31171051, 31371108, 31171274)
- 973 Projects of China (2012CB725203)
- Natural Science Foundation of Beijing (5112008, 5132007)
- General Program of Science and Technology Development Project of Beijing Municipal Education Commission of China (KM201110025001)
- Beijing Municipal Technology Foundation for Selected Overseas Chinese Scholar
- Capital Health Research and Development of Special (2014-1-4091)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
- Social Sciences › Cultural Studies › Language and cultural evolution
- Keywords
- axon guidance, vocal learning, speech and language disorders, netrin, semaphorins, de novo mutations, retinoic acid receptor signaling, FOXP2, single nucleotide polymorphisms, neurogenetics
- MeSH terms
- Axon Guidance, Netrin-1, Axons, Child, Child, Preschool, Humans, Language, Language Disorders, Learning, Male, Nerve Growth Factors, Speech, Receptors, Retinoic Acid, Evolution, Molecular, Mutation, Missense, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, Semaphorins, Forkhead Transcription Factors
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