Generalist genes and massive modularity
Recently Thomas wrote about a paper by Yulia Kovas and Robert Plomin in the May issue of TICS discussing the implications of the fact that a great number of genes – dubbed “generalist” genes – affect not one, but most cognitive abilities. One obvious implication is that, if most genes being expressed in the brain affect several areas of the brain, the massive modularity hypothesis (MMH) might not hold true. As Kovas and Plomin wrote in the conclusion to their paper:
Our opinion outlined in this article is that the generalist genes hypothesis is correct and that genetic input into brain structure and function is general (distributed) not specific (modular). The key genetic concepts of pleiotropy and polygenicity increase the plausibility of this opinion. Generalist genes have far-reaching implications for cognitive neuroscience because their pleiotropic and polygenic effects perfuse the transcriptome, the proteome and the brain. This is more than a ‘life-is-complicated’ message. DNA and RNA microarrays provide powerful tools that will ultimately make it possible for cognitive neuroscience to incorporate the trait-specific genome and transcriptome even if hundreds of genes affect individual differences in a particular brain or cognitive trait. The more immediate impact of generalist genes will be to change the way in which we think about the relationship among the genome, the transcriptome and the ‘phenome’ of the brain and cognition.
As Thomas was quick to remark, this idea is of course sure to infuriate proponents of the MMH. Therefore, it comes as no surprise that Gary Marcus and Hugh Rabagliati has a letter in next month’s TICS criticizing Kovas and Plomin’s article. Here is their argument for upholding the MMH:
Genes are in essence instructions for fabricating biological structure. In the construction of a house, one finds both some repeated motifs and some specializations for particular rooms. Every room has doors, electrical wiring, insulation and walls built upon a frame of wooden studs. However, the washroom and kitchen vary in the particulars of how they use plumbing array fixtures, and only a garage is likely to be equipped with electric doors (using a novel combination of electrical wiring and ‘doorness’). Constructing a home requires both domain-general and domain-specific techniques. The specialization of a given room principally derives from the ways in which high-level directives guide the precise implementation of low-level domain-general techniques. When it comes to neural function, the real question is how ‘generalist genes’ fit into the larger picture. Continuing the analogy, one might ask whether different ‘rooms’ of the brain are all built according to exactly the same plan, or whether they differ in important ways, while depending on common infrastructure. Kovas and Plomin presume that the sheer preponderance of domain-general genes implies a single common blueprint for the mind, but it is possible that the generalist genes are responsible only for infrastructure (e.g. the construction of receptors, neurotransmitters, dendritic spines, synaptic vesicles and axonal filaments), with a smaller number of specialist genes supervising in a way that still yields a substantial amount of modular structure.
The interesting thing about this discussion between Plomin and Marcus is the fact that the question that they raise can be investigated empirically, as Kovas and Plomin note in a reply to Marcus and Rabagliati:
Finding high genetic correlations means that genes must be generalists at the psychometric level at which
these traits have been assessed. Therefore, a genetic polymorphism that is associated with individual differences in a particular cognitive ability will also be associated with other abilities. The question is how these generalist genes work in the brain. Does a genetic polymorphism affect just one brain structure or function, which then affects many cognitive processes, as suggested by a modular view of brain structure and function (mechanism 1 in [Kovas and Plomin’s original article])? This model assumes that brain structures and functions are not genetically correlated – genetic correlations arise only at the level of cognition. Another possibility, which we think is more probable, is that the origin of the general effect of a genetic polymorphism is in the brain because the polymorphism affects many brain structures and functions (mechanisms 2 and 3 in [Kovas and Plomin’s original article]). Of course, some polymorphisms might have general effects via mechanism 1 and other polymorphisms might have general effects via mechanisms 2 and 3, as Marcus and Rabagliati suggest. Fortunately, this is an empirical issue about DNA polymorphisms that does not require resorting to metaphors such as house-building. We did not say that the case for mechanism 3 was proven, which is what Marcus and Rabagliati imply with their partial quote. The full quote from our article is: ‘In our opinion, these two key genetic concepts of pleiotropy and polygenicity suggest that the genetic input into brain structure and function is general not modular’. Pleiotropy (in which a gene affects many traits) is a general rule of genetics. Polygenicity (in which many genes affect a trait) is becoming another rule of genetics for complex traits and common disorders. As we point out, polygenicity greatly multiplies and magnifies the pleiotropic effects of generalist genes. A more empirical reason for suggesting that the origin of generalist genes is in the brain is that gene-expression maps of the brain generally indicate widespread expression of cognition related genes throughout the brain.
I second that sentiment. It would be a big step forward if the massively modularity discussion would move beyond mere speculation and become grounded in empirical data.
Kovas, Y. & Plomin, R. (2006): Generalist genes: implications for the cognitive sciences. Trends in Cognitive Science 10: 198-203.
Marcus, G. & Rabagliata, H (2006): Genes and domain specificity. Trends in Cognitive Science, in press.
Kovas, Y. & Plomin, R. (2006): Response to Marcus and Rabagliata. Trends in Cognitive Science, in press.