Behavioral Genetics II. 1h 32m Robert Sapolsky video.

After building our critical thinking skills in evaluating behavioral genetics studies in the previous lecture, Sapolsky now describes the modern approach to the field. Since the 1980s, the emphasis for any attribution of behavior to genetics has taken the mantra of "go and find the genes". This can be done by looking at two populations of traits or proteins and finding genetic markers. Or by starting with a gene and looking for traits that it expresses (this is problematic because the object of our study will tend to be the preferred explanation for any implicated phenotypic behavior rather than objectively searching for the factors contributing to that trait). He describes several genes whose behavioral effects are known, but admits they only explain a small part of the variation in behavior that exists.

Then he explains how the Nature / Nurture dichotomy is missing its third leg: chance! Chance plays a big role which he explains in terms of the mechanism of cell division itself. He spends most of the rest of the lecture trying to explain that "heritability" means the part of behavior that is NOT explained by genes (which he claims is not what most people think it means!). This discussion exposes the importance of the gene-environment interaction: all genes encode for if-then clauses about environmental effects! Fasten your seat belts, this discussion gets very strange and surprising at times! The bottom line is that the nature / nurture dichotomy is nonsense: genes act on the environment and vice versa: it is a both-neither situation!

Detailed Notes:

At first, finding the genes affecting behavior was done by statistically comparing the genomes of two populations (one with the trait and the other without it). Generally this means sifting through the genes to find a genetic marker (which is not the gene itself; and note that many diseases probably involve several genes). Approaches to examine two distinct proteins (by chemical or physical properties) have also been developed. Pat Brown at Stanford helped perfect the DNA microarray technique which can now coax a cell to transcribe all of its genes to RNA which can be used to make a biochip to assess genomic differences. QTL (quantitative trait loci) can be used to look at more complex genetic patterns.

The first successes came from diseases where the traits are clearly distinguished by "you've got it" or "you don't". Phenylketonuria (PKU), Huntington's disease, and cystic fibrosis were found to be genetic. Because these approaches are inherently statistical, there is always a possibility of false positives. This has spurred the development of extra care in the science (are you sure you got the statistics right?) and new work in bioethics: should we terminate this pregnancy if the child has a 94.2% chance of contracting Huntington's disease sometime between their teen years (unlikely) and old age (they may have lived a full healthy life before onset)? If someone just cared for their parent dying of a horrible genetic disease should we offer to test them and then have to tell them that there is a high (but not 100%) probability that they have the bad gene. What if they then jump from a tall building?

Some actual behavior affecting genes have been found. As discussed in the lecture on Molecular Genetics II, the vasopressin gene marker in voles distinguishes between monogamous and polygamous males. The same genes in humans affect how males handle social connectedness. The BDNF (brain-derived neurotrophic factor) gene prompts neural growth in the Amygdala (the part of the brain dealing with fear and anxiety). Variants of the BDNF gene studied in rats also explains human anxiety and depression. Dopamine receptor D4 also shows variations in rats and humans with similar effects in both species which explains human risk-taking, sensation-seeking, and novelty-craving behaviors. Neuropeptide Y (NPY) is a neurotransmitter with variants in its promoter which also has effects in the Amygdala. Sapolsky emphasizes that all of these genetic variations explain only tiny differences in the behavior.

The vital role of chance. Not all of the mitochondria in a cell are genetically identical. When the egg that becomes you splits in meiosis (sexual reproduction), roughly half of the mitochondria go into each daughter cell. Statistically, there is some chance that you will get a different mix of types of mitochondria from your mom. Moreover, at every mitotic cell division the mix of mitochondria may change. Not only does each daughter cell get a mix of mitochondria, but chance affects the mix of protein and transcription factors that make it into each daughter cell. Even if you know all the genes, you can't know where each molecule will be when the cell divides!

In behavioral genetic studies, the number that makes it into headlines is called "heritability": Y% of the variability in trait X is heritable. What does that mean? Sapolsky warns: not what you think!!! What heritability really means is now non-heritable the trait is! Heritability tells what genes have to do with the degree of variability observed in the trait. But then Sapolsky explains how science works: best practice dictates that you must control for extraneous environmental factors. That is, you don't run the experiment in the Gobi Desert, in a temperate climate, in the tropics, and at the poles. You just run it once and determine the heritability of the traits that are expressed in that environment. But this practically guarantees that the genetic component will be overestimated!!! So science is always giving us exaggerated values for heritability! Hmmph, even after getting down to the level of actual genes, behavioral genetics still falls quite far from "hitting the mark".

Then he discusses gene-environment interaction: genes behave differently depending on the environment. So it is impossible to say what a gene does, you can only say what the effect of a gene is in the environments studied so far! He gives an interesting example: the number of fingers you have is 5, 4, 3, 2, or 1 depending on how many accidents you have had. So the heritability of number of fingers is 0% (all variability is explained by industrial accidents). In 1952 Eisenhower America, there was a 0% change that a human male would have an earring and a 100% chance that, at that time, a human female would have an earring. So earrings were a 100% heritable trait! Heritability is a strange concept, no? Sapolsky concludes: it is meaningless to ask what a gene does as it can only be answered vis-a-vis the environment in which you test it. The genes code for environmental interactions, that's what they do!

Then he gives some more relevant examples of gene-environment interaction. In phenylketonuria (PKU) the body's ability to metabolize the amino acid phenylalanine is genetically missing. The phenylalanine builds up and destroys your brain. This is a 100% heritable trait. By eating a diet that severely restricts or eliminates foods with phenylalanine in them, patients can lead healthy lives! A heritable trait which environment can control? Doesn't that mean that heritability should be 0%? This is truly weird!

From animal studies on serotonin (a neurotransmitter) a genetic variant leads to more depression (via an interaction with glucocorticoid stress hormones). But in humans it was discovered that the effect is mediated by a gene-environment interaction: the number of environmental stress events (childhood traumas such as losing a parent). Surprisingly, the "bad" gene results in fewer(!) depressions if you had no childhood traumas. In animal studies a variant of the enzyme monoamine oxidase (MAO) predisposes subjects to more aggression than the other variant. In humans a study suggests that it is correlated with antisocial (what used to be called sociopathic) behavior. A similar effect is seen with another serotonin factor, but that one is mediated by child abuse. Another study has a gene mediating social attachment if and only if the mother is cold and withdrawn. Another gene gives some predictability for IQ if and only if the subject was breast fed.

Sapolsky cites Paul Ehrlich for the quote "asking whether genes or environment have more to do with some trait is akin to asking whether length or width have more to do with the area of a rectangle" (Wikipedia credits Donald Hebb with a similar quote; I modified Sapolsky's version to be mathematically accurate). There is no such thing as a gene influence outside the context of an environmental interaction.

Many, many studies have shown that having a Y chromosome (that is, being male) predicts better math skills. Paola Sapienza and colleagues analyzed data from a test designed by the OECD and administered in 40 countries to 276,165 15-year olds. She discovered that the gender gap is mediated according to a country's score on the The World Economic Forum's Gender Gap Index (GGI). Iceland even has females outperforming males in math and two Scandinavian countries were at statistical parity. It turns out that males tend to outperform females at math in those societies with a gender gap!  Here is the math study if you are interested:

My conclusion: Nature / Nurture is another one of those "both-neither" phenomena!

In lecture 5 on Molecular Genetics II, Sapolsky discussed the work of Dmitri Belyaev's team in "domesticating" the silver fox in some 35 generations. He starts this lecture by describing the street dogs of Moscow studied by Andrei Poyarkov who has observed that over time these dogs have reacquired wolf-like characteristics such as a longer muzzle, more erect ears, loss of a piebald coloration.

7. Behavioral Genetics II