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This post was chosen as an Editor's Selection for ResearchBlogging.orgThe FOXP2 gene is well-known for its involvement in language disorders. We are just getting ready to publish our discovery that a relative of this gene in the fruit fly Drosophila, dFoxP, is necessary for a learning mechanism that resembles language learning in a lot of ways, operant self-learning. This discovery traces one of the evolutionary roots of language back to the 'Urbilaterian', the last common ancestor of invertebrates and vertebrates, more than half a billion years before the first word was ever spoken. A remarkable pre-adaptation (‘exaptation’) for language.

Intriguingly, dFoxP-function also differentiates between self and non-self: forms of learning in which the animals had to learn about their environment, rather than about their own behavior, were unaffected by our manipulations of dFoxP function.
While we were writing up the results for our manuscript, I stumbled across two papers by Bernard Crespi. The first detailed a hypothesis of how autism and schizophrenia may be conceived as two diametrically opposite ends of a continuous spectrum, the other was a test of that hypothesis. From their abstract:
We used data from studies of copy-number variants (CNVs), single-gene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partial overlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance.[...]These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain. 
So basically, one of the things they looked at was whether there were any genes implicated in both autism and schizophrenia. For the genes they found, they tested if different variants of these genes would be associated specifically with each disorder. Finally, they tested whether the nature of the genetic differences would say anything about the potential dysregulations of gene function involved in the two disorders.

Most relevant for us was that FOXP2 showed up in their study:
for the genes AHI1, APOE, DRD1, FOXP2, HLA-DRB1, and SHANK3, alternative alleles, genotypes, or haplotypes at the same loci appear to mediate risk of these two conditions.
Which means that the FOXP2 gene in humans is associated with both autism and schizophrenia, but that some variants of the gene are specifically associated with autism and not with schizophrenia, while the opposite holds for other variants.

What is the spectrum that Crespi et al. hypothesize autism and schizophrenia might be the opposite end points of? In their own words:
Under-development of social phenotypes such as theory of mind, language, sense of self in relation to others, and reciprocal social interaction represent well-recognized manifestations of autism. [...]By contrast, such psychotic traits as auditory hallucination and thought disorder, paranoia, megalomania, and ascription of causal purpose to inanimate objects may be interpretable in terms of dysregulated hyperdevelopment of language, theory of mind and sense of self, all traits that are highly derived and elaborated in the human lineage.
The important component of these factors Crespi et al. enumerate with respect to FoxP function is of course 'sense of self'. Is it really a coincidence that even in flies dFoxP function differentiates between self and non-self, a key process malfunctioning in autism and schizophrenia, or is the genetic network in which FoxP is embedded highly conserved through evolution (i.e., a case of 'deep' homology)?



Crespi, B., Stead, P., & Elliot, M. (2009). Comparative genomics of autism and schizophrenia Proceedings of the National Academy of Sciences, 107 (suppl_1), 1736-1741 DOI: 10.1073/pnas.0906080106
Posted on Friday 04 November 2011 - 10:28:34 comment: 0
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