Conley Dalton, Rauscher Emily, Siegal Mark L
Department of Sociology, New York University, New York , NY, USA.
Biodemography Soc Biol. 2013;59(1):37-56. doi: 10.1080/19485565.2013.774620.
The persistence of behaviorally deleterious genes in the human population poses an interesting question for population genetics: If certain alleles at these loci are deleterious, why have they survived in the population? We consider evidence for phenotypic capacitance and/or frequency-dependent selection for an allele that has been putatively shown to have negative associations with human behaviors (the "short" 5-HTT promoter region allele) yet has persisted in human and nonhuman primate populations. Using data from the National Longitudinal Study of Adolescent Health, we compare sibling and twin variation in depression by 5-HTT genotype (specified in several ways) and investigate sibship-level cross-person gene-gene interactions. In support of the "orchid/dandelion" hypothesis, we find evidence that the short allele increases variation in phenotypes in response to environmental (or genetic) differences (i.e., acts as a perturbation of a phenotypic capacitor). Further, we also find some evidence that the effects of allelic variation at this locus are moderated by the genetic environment of the sibship unit (i.e., effects may be susceptible to frequency-dependent selection). We discuss implications of these findings for genetic models in general, specifically with respect to stable unit treatment value assumption violations (i.e., nonindependence of units of analysis).
如果这些基因座上的某些等位基因是有害的，为什么它们在群体中得以留存？我们考虑了关于表型电容和/或频率依赖性选择的证据，该证据涉及一个被推测与人类行为存在负相关的等位基因（“短”5-羟色胺转运体启动子区域等位基因），然而它却在人类和非人类灵长类群体中持续存在。利用来自青少年健康全国纵向研究的数据，我们按5-羟色胺转运体基因型（以多种方式指定）比较了兄弟姐妹和双胞胎在抑郁方面的差异，并研究了同胞层面个体间的基因-基因相互作用。为支持“兰花/蒲公英”假说，我们发现证据表明，短等位基因会随着环境（或基因）差异增加表型变异（即，起到表型电容器的扰动作用）。此外，我们还发现一些证据表明，该基因座上等位基因变异的效应受到同胞单元基因环境的调节（即，效应可能易受频率依赖性选择的影响）。我们讨论了这些发现对一般遗传模型的意义，特别是关于稳定单元治疗值假设违背（即分析单元的非独立性）方面的意义。
