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      Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain

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          Abstract

          Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the “domestication syndrome” (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the “domestication syndrome” and, ultimately, from the normal functioning of the neural crest.

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          STRING v10: protein–protein interaction networks, integrated over the tree of life

          The many functional partnerships and interactions that occur between proteins are at the core of cellular processing and their systematic characterization helps to provide context in molecular systems biology. However, known and predicted interactions are scattered over multiple resources, and the available data exhibit notable differences in terms of quality and completeness. The STRING database (http://string-db.org) aims to provide a critical assessment and integration of protein–protein interactions, including direct (physical) as well as indirect (functional) associations. The new version 10.0 of STRING covers more than 2000 organisms, which has necessitated novel, scalable algorithms for transferring interaction information between organisms. For this purpose, we have introduced hierarchical and self-consistent orthology annotations for all interacting proteins, grouping the proteins into families at various levels of phylogenetic resolution. Further improvements in version 10.0 include a completely redesigned prediction pipeline for inferring protein–protein associations from co-expression data, an API interface for the R computing environment and improved statistical analysis for enrichment tests in user-provided networks.
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            The complete genome sequence of a Neandertal from the Altai Mountains

            We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans.
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              A high-coverage genome sequence from an archaic Denisovan individual.

              We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                29 August 2016
                2016
                : 10
                : 373
                Affiliations
                [1] 1Department of Philology, University of Huelva Huelva, Spain
                [2] 2Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy
                [3] 3Division of Psychology and Language Sciences, University College London London, UK
                Author notes

                Edited by: Yuri Bozzi, University of Trento, Italy

                Reviewed by: Suhash Chakraborty, Hindustan Aeronautics Limited Hospital, India; Roberto Canitano, University Hospital of Siena, Italy

                *Correspondence: Elliot Murphy elliotmurphy91@ 123456gmail.com

                This article was submitted to Child and Adolescent Psychiatry, a section of the journal Frontiers in Neuroscience

                †These authors have contributed equally to this work.

                Article
                10.3389/fnins.2016.00373
                5002430
                27621700
                5705ae32-c696-4281-ae78-02459a5f650d
                Copyright © 2016 Benítez-Burraco, Lattanzi and Murphy.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 April 2016
                : 02 August 2016
                Page count
                Figures: 6, Tables: 3, Equations: 0, References: 285, Pages: 23, Words: 19687
                Categories
                Neuroscience
                Hypothesis and Theory

                Neurosciences
                autism,domestication,language evolution,neural oscillations,language deficits
                Neurosciences
                autism, domestication, language evolution, neural oscillations, language deficits

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