Identifying Genetic and Environmental (G X E) Factors in Populations

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene,” by Avshalom Caspi et all, Science, 18 July 2003, http://www.sciencemag.org/cgi/content/abstract/sci;301/5631/386.

Experiments Investigating Cooperative Types in Humans: A Complement to Evolutionary Theory and Simulations,” by Robert Kurzban and Daniel Houser, PNAS, 1 February 2005, http://www.pnas.org/cgi/content/abstract/102/5/1803.

“Microsatellite Instability Generates Diversity in Brain and Sociobiological Traits,” by Elizabeth Hammock and Larry Young, Science, 10 June 2005, 308 1630-1634.

Ancient and Recent Positive Selection Transformed Opioid cis-Regulation in Humans,” by Matthew Rockman et al, PLoS Biology, December 2005, http://biology.plosjournals.org/perlserv?request=get-document&doi=10.1371/journal.pbio.0030387.

Still Evolving, Human Genes Tell New Story,” by Nicholas Wade, New York Times, 7 March 2006, http://www.nytimes.com/2006/03/07/science/07evolve.html.

Notes for this week are these five six (Kurzban’s already being referenced in his talk, likewise Hibbing’s (and Alford’s) in his talk), as well as Adapting Minds by David Buller.

I was especially interested in lines of research that shed light on how to use G X E to fight insurgencies. (If all goes well, my final paper in this class will be on System Administration for Phenotypes).


“Individuals with one or two copies of the short allele of the 5-HTT promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful live events than individuals homozygous for the long allele.” (Caspi et all 386)

“Across the life span, stressful live events that involve threat, loss, humiliation, or defeat influence the onset and course of depression. However, not all people who encounter a stressful life experience succumb to its depressogenic effect. Diathesis-stress theories of depression predict that individuals’ sensitivity to stressful events depends on their genetic makeup.” (Caspi et all 386)

“Although the 5-HTT gene may not be directly associated with depression, it could moderate the serotonergic response to stress. Three lines of experimental research suggest this hypothesis of a gene-by-environment (G X E) interaction.” (Caspi et all 387)

“We tested this G X E hypothesis among members of the Dunedin Multidisciplinary Health and Development Study. This representative birth cohort of 1037 children (52% male) has been assessed at ages 3,5,7,9,11,13,15,18, and 21 and was virtually intact (96%) at the age of 26 years.” (Caspi et all 387)

“Nonetheless, although carriers of an s 5-HTTLPR allele who experienced four or more life events constituted only 10% of the birth cohort, they accounted for almost one-quarter (23%) of the 133 cases of diagnosed depression.” (Caspi et all 389)

“Although the short 5-HTTLPR variant is too prevalent for discriminatory screening (over half of the Caucasian population has an s allele), a microarray of genes might eventually identify those needing prophylaxis against life’s stressful events.” (Caspi et all 389)

“Our findings of G X E interaction for the 5-HTT gene and another candidate gene, MAOA, point to a different, evolutionary model. This model assumes that genetic variants maintained at high prevalence in the population probably act to promote organisms’ resistance to environmental pathogens.” (Caspi et all 389)

“A key result from simulations is that population, instead of evolving toward agents with homogeneous behavioral strategies, often evolve such that multiple strategies coexist at equilibrium.” (Kurzban and Houser 1803)

“The laboratory experiment reported here complements simulations by exploring type stability in a potentially fickle human population. In line with types used in simulations and observed in other experimental contexts, we consider the hypothesis that people are one of three stable types: (i) cooperators, who contribute to generating group benefits at a cost to self, (ii) free-riders, who do not incur these costs, and (iii) reciprocators, who respond to others’ behavior by using a conditional strategy.” (Kurzban and Houser 1803)

“The dynamics of agent-based simulations are sensitive to the fraction of types in the population and the frequency with which these types interact.” (Kurzban and Houser 1803)

“Our approach to behavioral-type classification is to prespecify a set of behaviors of interest, and then assign of from this set to each subject. This sort of approach was used, for example, by El-Gamal and Grether in their well known behavioral typing algorithm. Although more sophisticated (and cumbersome) procedures are available, the advantage of our classification algorithm is that it provides a simple, fast, and accurate method for inference about individual differences, after which any analysis can be conducted.” (Kurzban and Houser 1804)

“To investigate whether individual differences in our experiment are stable, when time allowed we had subjects play up to three additional games, again with randomly reassigned partners… Overall then, our results provide evidence that types in our experiment are different from one another and stable over time.” (Kurzban and Houser 1805)

“Our results provide evidence that there are multiple, stable behavioral types that vary with respect to their disposition to cooperate in a group context. Fishbacher, Gachter, and Fehr, having found evidence of both free-riding and conditionally cooperative strategies, suggested that groups that include both types might be expected to experience cooperative decay and convergence to a noncooperative equilibrium, and then speculated that ‘the speed of convergence depends on the actual composition of the group.’” (Kurzban and Houser 1805-1806)

“It is interesting to note that social psychologists and economists have postulated similar classification systems. The research tradition in social psychology on social value orientation, for example, suggests that people can be classified as competitors (motivated to achieve better payoffs than others), cooperators (motivated to try to increase group welfare), and individualists (motivated to serve their own interests).” (Kurzban and Houser 1806)

“Nonetheless, our results add to the growing body of research that suggests that reciprocity is an important motive in group contexts across a range of institutional arrangements.” (Kurzban and Houser (1807)

“Repetitive microsatellites mutate at relatively high rates and may contribute to the rapid evolution of species-typical traits.” (Hammock and Young 1630)

“Evolution of species-typical behavioral traits requires behavioral diversity and a polymorphic genetic mechanism producing such diversity. The high levels of polymorphism in repetitive DNA sequences (microsatellites) make them useful as markers to distinguish among individuals.” (Hammock and Young 1630)

“The rait of substitution (k) is equal to the rate at which new mutations arise in the population (2 * Ne * u) times the probability that a new mutation will become fixed, which is 1 / 2 * Ne for neural mutations and approximately 2s for advantageous mutations in a population of constant size, where Ne is the effective population size, u is the mutation rate, and s is the selective advantage of the mutant allele.” (Rockman et al 2210-2211).

“Positive selection driving differentiation between populations should also decrease variation with in populations; as a selected allele increases in frequency, its haplotype replaces other haplotypes before accumulating new variations.” (Rockman et al 2214)

“For thousands of years, people have used opiates to alter consciousness and ameliorate pain. Our data indicate that the evolution of our species involved changes in the inducibility of an endogenous opioid precursor, and that these changes were driven by positive natural selection.” (Rockman et al 2215)

“Three populations were studied, Africans, East Asians, and Europeans. In each, a mostly different set of genes had been favored by natural selection.” (Wade)

“Dr. Pritchard estimates that the average point at which the selected genes started to become more common under pressure of natural selection is 10,800 years ago in the African population and 6,600 years ago in the Asian and European populations.” (Wade)

“The selected genes turned out to be quite different from one racial group to another. Dr. Pritchard’s test identified 206 regions of the genome that are undre selection in the Yorubans, 185 regions in East Asians, and 188 in Europeans. The few overlaps between races concern genes that could have been spread by migration or else be instances of independent evolution, Dr. Pritchard said.” (Wade)

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