How biologists think about genes

From Tangled webs: Tracing the connections between genes and cognition, by Simon E. Fisher:

The deceptive simplicity of finding correlations between genetic and phenotypic variation has led to a common misconception that there exist straightforward linear relationships between specific genes and particular behavioural and/or cognitive outputs. The problem is exacerbated by the adoption of an abstract view of the nature of the gene, without consideration of molecular, developmental or ontogenetic frameworks. ... Genes do not specify behaviours or cognitive processes; they make regulatory factors, signalling molecules, receptors, enzymes, and so on, that interact in highly complex networks, modulated by environmental influences, in order to build and maintain the brain. ...

What is a gene? Answering this question is far from trivial, but a useful operational definition might be ‘‘a stretch of DNA whose linear sequence of nucleotides encodes the linear sequence of amino acids in a specific protein’’. ... It is important to realise that the appearance and biology of a mature organism is the result of a complex series of ontogenetic events unfolding over time, moderated by environmental and stochastic influences. Genomes are much more like knitting patterns or recipes than blueprints (although even the former are poor analogies for the peculiarities of the genome). ...

The apparent ease of correlating genotype with phenotype without reference to molecular/developmental mechanisms promotes an erroneous impression of neurogenetics; one in which individual genes are able to mysteriously control specific behaviours or cognitive abilities, leading to talk of ‘‘language genes’’, ‘‘smart genes’’, ‘‘gay genes’’, ‘‘aggressive genes’’ and so on. It is indisputable that variations of gene sequence can contribute to variability in cognitive abilities and personality traits (sometimes in a dramatic manner) and that apparently straightforward genotype-phenotype correlations can sometimes emerge in our datasets. But the simplicity of these relationships is merely an illusion; genes do not (and indeed can not) specify particular behavioural outputs or cognitive processes, except in the most indirect way. ... The gross activities of the human brain are the products of a complex interplay between factors at multiple levels; be they genetic, cellular, developmental, anatomical, or environmental, and the routes linking genes to cognition will inevitably be tortuous...

... the gap between genes and cognition can only be bridged by a thorough systems biology account of brain development and function. Even pure candidate gene approaches can be victims of the ‘‘abstract gene’’ perspective. In many cases, when researchers find statistical evidence to support association between a particular variant of a gene and a common trait, it is erroneously assumed on the basis of this that the variant is likely to be causative and that there is a simple pathway connecting gene to trait. ... There is a large gulf between finding statistical evidence for a genotype-phenotype correlation and demonstrating a convincing causal relationship...

There is no doubt that the gene known as FOXP2 is relevant to linguistic ability. However, any characterisation of this as a ‘‘gene for grammar’’ clearly becomes untenable once we are able to view it within a more complete biological framework. ... Reduced amounts of functional FOXP2 protein can lead to disordered brain development or function, in a manner that primarily interferes with speech and/or language abilities. ... this is emphatically not the same as saying that FOXP2 is a ‘‘gene for speech’’ or a ‘‘gene for language’’... FOXP2 [also] regulates key pathways in the developing lung, heart and gut. .... The recycled use of the same regulatory factors to control multiple pathways in different developmental contexts is a common feature of complex biological systems; it is rare to find a transcription factor that has an exclusive role specific to only one context. Thus, calling FOXP2 a ‘‘language gene’’ makes no more sense than referring to it as a ‘‘lung gene’’... the data on FOXP2 from molecular and developmental biology confounds any expectations that one might have for a hypothetical ‘‘language gene’’; and the reason for this is that this entire concept is flawed, being rooted in an abstract view of the nature of the gene. ...