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Saturday, May 19, 2012

Gotta Have a Gene for This, a Gene for That

But this running with the genes just ain't where it's at...

A great paper in the current issue of American Political Science Review, "Candidate Genes and Political Behavior" by Charney and English, takes down the contemporary trend in the social sciences to find a gene that makes one vote Republican, a "God gene," a gene that makes you trade on Wall Street, and so on. The major problem is that all of the studies is that they rely on a false, reductionist view of the gene that has been massively discredited over the last few decades in biology. Some key quotes:
Genes do not regulate the extent to which they are capable of being transcribed in any obvious, unidirectional manner. Rather, the extent to which a gene can be transcribed is controlled by the epigenome, the complex biochemical regulatory system that turns genes on and off, is environmentally reponsive, and can influence phenotype via environmentally induced changes to gene transcribability8 with no changes to the DNA sequence (Jirtle and Skinner 2007). As neuroscientist Mark Mehler (2008, 602) notes in regard to the epigenome and epigenomics, “We are in the midst of a revolution in the genomic sciences that will forever change the way we view biology and medicine, particularly with respect to brain form, function, development, evolution, plasticity, neurological disease pathogenesis and neural regenerative potential.”
Hence, a single gene can code for multiple proteins, something that is estimated to occur in 90% of all human genes. We cannot equate a particular allele straightforwardly with the production of a particular form of a protein and from that with the production.

The old reductionist model of DNA, in which it controls the phenotype as if it were a blueprint from which house plans are read off? Out the window:
Once considered the paragon of stability, DNA is subject to all manner of transformation. For example, retrotransposons or “jumping genes” comprise 45% of the human genome, move about the genome by a copy-and-paste mechanism chang- ing DNA content and structure, are regulated by the epigenome (and hence are potentially environ- mentally responsive), and appear to be particularly prevalent in the human brain (Coufal et al. 2009). Once dismissed as “junk DNA” and “selfish par- asites” (Dawkins 2006), retrotransposons are now deemed an essential component of normal human development and functioning (Walters, Kugel, and Goodrich 2009). 

Height might seem to be the simple sort of thing that would be determined through a simple Mendelian model of inheritance, right? Well, no:
Height is a highly heritable trait: 80% of the variation in height in a given population at a given time is attributable to genetic factors. A new, exceptionally large study involving full genome scans (genome-wide association [GWA] studies) of more than 180,000 individuals identified 180 genomic regions that influence adult height (Lango Allen et al. 2010). However, the variants on these 180 genes, considered together, explain only 10% of the heritable phenotypic variation in height in a given population, with no variant explaining more than a tiny fraction of a percent of variation.
Genetic reductionism, it has become apparent, was an ideology, and our actual biology does not care what are our ideological beliefs:
The dogma in molecular genetics until the 1990s was that genotype would predict phenotype. We thought that once we cloned and characterized the gene, then the nature of the mutation in the gene would specify the individual’s phenotype. . . . This concept celebrated reductionism. However, nature had not informed the patients and their biology of this belief system. Not only could we not predict phenotype for genotype for GK and AHC [two monogenic disorders], similar observations were being made by others for many rare [monogenic] genetic disorders (McCabe and McCabe 2006, 160).
But since social science researchers are often unaware of these findings in biology, they conduct their studies as though they can just hunt through massive databases of genetic and behavioral information, and read straight off relationships between single genes and complex human behaviors (even though an organism as simple as the fruit fly has at least 266 different genes that influence aggressive behavior), so that, for instance, we get alleles of the gene MAOA said, in various studies, to be causing, amongst other things: agreeableness, alcoholism, Alzheimer's, anorexia, autism, binge drinking, bipolar disorder, bone mineral density, chronic fatigue, contraceptive use, credit card debt, extraversion, fraudulent behavior, gang membership, gout, hypertension, insomnia, narcolepsy, novelty seeking, obesity, OCD, restless leg syndrome, smoking, SIDS, and voting behavior (and this is a partial list!). So, in a fruit fly, 266 different genes influence aggressive behavior, but in humans, variations in a single gene have a significant impact on all of the above? Or is it more likely that these correlations are the simple effect of the fact that, if one goes on "correlation fishing expeditions" through any massive database, all sorts of spurious correlations will appear?

The authors conclude:

Given that every new advance in the science of genetics adds yet another layer of complexity (at which we have merely hinted), we have the strongest reasons to doubt that a handful of candidate genes will pro- vide a meaningful key to understanding differences in voting behavior, political ideology, or attitudes toward abortion. Advances in genomic science suggest that this reductionist approach is ill conceived...

6 comments:

  1. This is a pet peeve of mine, and what's worse, most newspaper editors are absolutely terrible at reporting on genetics. Every hint of any correlation between genetics and behavior, however slight or inconclusive, is mangled into "Scientists find gene that determines whether men like blondes or brunettes".

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  2. Exactly right! And as I'm sure you've noted, a great portion of these behaviors and mindset flow from positivism, of which I'm not sure there was ever a more stereotypical demonstration of its approach (and futility) than the Human Genome Project. How many promises were made that we'd understand practically everything once the thing had been completely sequenced, and almost as soon as the deed was done, it was explained that it would take many more human sequences to figure out what everything did.

    Useful as sequence information is when you've already got an idea how things work, theoretical and hypothesis driven research are probably better suited to the figuring out. But I'm beginning to think that biology probably has more in common with meteorology than with chemistry -- the systems involved are simply so complex that they'll never really be reducible to the kind of attractive abstractions and equations you find in subjects like chemistry and physics. We'll always be kind of guessing. Maybe we'll get close with bacteria, but eukaryotes probably never.

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  3. This is a bigger problem for the popular press reporting on behavioral genetics than behavioral genetics itself.

    If you go back to the 1970s with Dawkins, there was little pretense that we would be able to identify "the" gene for something. But that isn't the same thing as saying you cannot argue that something is genetic, despite what the authors imply, if genetic means "nature" as opposed to "nurture."

    If you want to see a work that pays lip service to the whole "it's complicated" thing, see (your least favorite author) Matt Ridley's Nature via Nurture, which preserves every interesting result in behavioral genetics without running into any of the problems raised by the paper (which are really skin deep). Note also this was a popular book from a decade ago, so it's not exactly like serious people aren't aware of these things.

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    1. This comment has been removed by the author.

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    2. "But that isn't the same thing as saying you cannot argue that something is genetic, despite what the authors imply..."

      Wow, Ryan, not only did you not read the paper I am citing, you didn't even read the excerpts from the paper I explicitly included in this post:


      "80% of the variation in height in a given population at a given time is attributable to genetic factors."

      So since the authors very explicitly argue that we can say 80% of the variation in height is genetic, why do you say that they "imply" that we can't argue that something is genetic?! Is it possible to misread an author's work more egregiously?

      Given that you could not even bear to superficially scan the quotes I gave from the paper in question, I will take your assertion that the problem the paper raises are only "really skin deep" as merely an assertion of your faith in the reductionist paradigm, despite all evidence of its repeated failure, since you obviously have not only not read the paper in question but did not even really read the quotes I excerpted from the paper.

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    3. "This is a bigger problem for the popular press reporting on behavioral genetics than behavioral genetics itself."

      Oh, and since the authors list literally hundreds of academic studies with this problem...

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