Ancient roots: A Cambrian explosion of autism susceptibility genes
Open accessAbstract
Functional gene groups often share unique evolutionary patterns. The present study addresses whether autism susceptibility genes, which frequently share functional overlap, display unusual gene age and conservation patterns compared to other gene groups. Using phylostratigraphically‐derived and other genetic data, the investigator explores average gene age, Ohnolog status, evolutionary rate, variation intolerance, and numbers of protein–protein (PPI) interactions across autism susceptibility, nervous system, developmental regulatory, immune, housekeeping, and luxury gene groups. Autism susceptibility genes are unusually old compared to controls, many genes having radiated in the Cambrian period in early vertebrates from whole genome duplication events. They are also tightly conserved across the animal kingdom, are highly variation intolerant, and have more PPI than other genes—all features suggesting extreme dosage sensitivity. The results of the current study indicate that autism susceptibility genes display unique radiation and conservation patterns, which may be a reflection of the major transitions in nervous system evolution that were occurring in early animals and which are still foundational in brain development today.
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Brain-related genes, including major effect genes implicated in autism, are tightly conserved and generally mutation intolerant as a result of dosage sensitivity [38].
“However, it has previously been recognized that brain-related genes, including major effect genes implicated in autism, are tightly conserved and generally mutation intolerant as a result of dosage sensitivity [38].”
From Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings (2024) · cites this paper as [38]
Cites
The mutational constraint spectrum quantified from variation in 141,456 humans
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., et al. (2020) · Nature · doi:10.1038/s41586-020-2308-7 · Cited by 9,434 · see citing works
Mi, H., Muruganujan, A., Ebert, D., Huang, X., & Thomas, P. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1038 · Cited by 2,950 · see citing works
Cunningham, F., Allen, J. E., Allen, J., Alvarez-Jarreta, J., Amode, M. R., Armean, I. M., Austine-Orimoloye, O., Azov, A. G., Barnes, I., Bennett, R., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1049 · Cited by 1,923 · see citing works
The mutational constraint spectrum quantified from variation in 141,456 humans
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., et al. (2019) · doi:10.1101/531210 · Cited by 1,662 · see citing works
Human housekeeping genes, revisited
Eisenberg, E., & Levanon, E. Y. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.05.010 · Cited by 1,249 · see citing works
InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation
Breuer, K., Foroushani, A. B. K., Laird, M. R., Chen, C. C. L., Sribnaia, A., Lo, R., Winsor, G. L., Hancock, R. E. W., Brinkman, F. S. L., & Lynn, D. J. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1147 · Cited by 1,224 · see citing works
Kriventseva, E. V., Kuznetsov, D. A., Tegenfeldt, F., Manni, M., Dias, R. O., Simão, F. A., & Zdobnov, E. M. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1053 · Cited by 1,138 · see citing works
SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs)
Abrahams, B. S., Arking, D. E., Campbell, D. B., Mefford, H. C., Morrow, E. M., Weiss, L. A., Menashe, I., Wadkins, T., Banerjee-Basu, S., & Packer, A. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-36 · Cited by 873 · see citing works
CORUM: the comprehensive resource of mammalian protein complexes—2019
Giurgiu, M., Reinhard, J., Brauner, B., Dunger-Kaltenbach, I., Fobo, G., Frishman, G., Montrone, C., & Ruepp, A. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky973 · Cited by 595 · see citing works
Ohnologs in the human genome are dosage balanced and frequently associated with disease
Makino, T. T., & McLysaght, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914697107 · Cited by 274 · see citing works
Profiling cellular diversity in sponges informs animal cell type and nervous system evolution
Musser, J. M., Schippers, K. J., Nickel, M., Mizzon, G., Kohn, A. B., Pape, C., Ronchi, P., Papadopoulos, N., Tarashansky, A. J., Hammel, J. U., et al. (2021) · Science · doi:10.1126/science.abj2949 · Cited by 242 · see citing works
Puelles, L., & Rubenstein, J. L. R. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00027 · Cited by 204 · see citing works
What nervous systems do: early evolution, input–output, and the skin brain thesis
Keijzer, F., van Duijn, M., & Lyon, P. (2013) · Adaptive Behavior · doi:10.1177/1059712312465330 · Cited by 173 · see citing works
Origins of neurogenesis, a cnidarian view
Galliot, B., Quiquand, M., Ghila, L., de Rosa, R., Miljkovic-Licina, M., & Chera, S. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.05.563 · Cited by 168 · see citing works
Feinberg, T. E., & Mallatt, J. (2013) · Frontiers in Psychology · doi:10.3389/fpsyg.2013.00667 · Cited by 158 · see citing works
Singh, P. P., & Isambert, H. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz909 · Cited by 88 · see citing works
Olfaction, navigation, and the origin of isocortex
Aboitiz, F., & Montiel, J. F. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00402 · Cited by 53 · see citing works
Functional origins of the vertebrate cerebellum from a sensory processing antecedent
Montgomery, J. C., & Bodznick, D. (2010) · Current Zoology · doi:10.1093/czoolo/56.3.277 · Cited by 17 · see citing works
Albuixech-Crespo, B., Herrera-Úbeda, C., Marfany, G., Irimia, M., & García‐Fernàndez, J. (2017) · The International Journal of Developmental Biology · doi:10.1387/ijdb.170258jg · Cited by 10 · see citing works
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Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings
Pauly, R., Johnson, L., Feltus, F. A., & Casanova, E. L. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02593-7 · Cited by 7 · see citing works
Self-citation
- Authors
- Casanova, E. L.
- Affiliations
- Department of Psychology Loyola University New Orleans Louisiana USA
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2023-07-08
- Volume
- 16
- Issue
- 8
- Pages
- 1480-1487
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- OpenAlex
- W4383615395
- Cited by
- 5
- References
- 20
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- autism susceptibility genes, gene age, genetic conservation, phylostratigraphy, ohnologs, whole-genome duplication, protein-protein interaction, dosage sensitivity, nervous system evolution, Cambrian explosion, vertebrate evolution, brain development
- MeSH terms
- Autism Spectrum Disorder, Animals, Autistic Disorder, Vertebrates, Genome, Evolution, Molecular, Gene Duplication
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