Mokkonen Mikael, Crespi Bernard J
Department of Biological Sciences, Simon Fraser University Burnaby, BC, Canada ; Department of Biological and Environmental Science, University of Jyväskylä Jyväskylä, Finland.
Department of Biological Sciences, Simon Fraser University Burnaby, BC, Canada.
Evol Appl. 2015 Apr;8(4):307-25. doi: 10.1111/eva.12244. Epub 2015 Feb 4.
We review the hypothesized and observed effects of two of the major forms of genomic conflicts, genomic imprinting and sexual antagonism, on human health. We focus on phenotypes mediated by peptide and steroid hormones (especially oxytocin and testosterone) because such hormones centrally mediate patterns of physical and behavioral resource allocation that underlie both forms of conflict. In early development, a suite of imprinted genes modulates the human oxytocinergic system as predicted from theory, with paternally inherited gene expression associated with higher oxytocin production, and increased solicitation to mothers by infants. This system is predicted to impact health through the incompatibility of paternal-gene and maternal-gene optima and increased vulnerability of imprinted gene systems to genetic and epigenetic changes. Early alterations to oxytocinergic systems have long-term negative impacts on human psychological health, especially through their effects on attachment and social behavior. In contrast to genomic imprinting, which generates maladaptation along an axis of mother-infant attachment, sexual antagonism is predicted from theory to generate maladaptation along an axis of sexual dimorphism, modulated by steroid and peptide hormones. We describe evidence of sexual antagonism from studies of humans and other animals, demonstrating that sexually antagonistic effects on sex-dimorphic phenotypes, including aspects of immunity, life history, psychology, and behavior, are commonly observed and lead to forms of maladaptation that are demonstrated, or expected, to impact human health. Recent epidemiological and psychiatric studies of schizophrenia in particular indicate that it is mediated, in part, by sexually antagonistic alleles. The primary implication of this review is that data collection focused on (i) effects of imprinted genes that modulate the oxytocin system, and (ii) effects of sexually antagonistic alleles on sex-dimorphic, disease-related phenotypes will lead to novel insights into both human health and the evolutionary dynamics of genomic conflicts.
我们回顾了两种主要形式的基因组冲突——基因组印记和性拮抗，对人类健康的假设影响和观察到的影响。我们关注由肽类和类固醇激素（尤其是催产素和睾酮）介导的表型，因为此类激素在中枢调节身体和行为资源分配模式，而这两种冲突形式均以此为基础。在早期发育过程中，正如理论预测的那样，一组印记基因调节着人类的催产素能系统，父系遗传的基因表达与更高的催产素产生相关，且婴儿对母亲的索求增加。预计该系统会通过父系基因和母系基因最优状态的不匹配以及印记基因系统对遗传和表观遗传变化的更高易感性来影响健康。催产素能系统的早期改变会对人类心理健康产生长期负面影响，尤其是通过其对依恋和社会行为的影响。与在母婴依恋轴上产生适应不良的基因组印记不同，理论预测性拮抗会在性二态性轴上产生适应不良，由类固醇和肽类激素调节。我们描述了来自人类和其他动物研究中性拮抗的证据，表明对性二态性表型的性拮抗作用，包括免疫、生活史、心理和行为等方面，普遍存在，并导致已证明或预期会影响人类健康的适应不良形式。特别是最近关于精神分裂症的流行病学和精神病学研究表明，它部分是由性拮抗等位基因介导的。本综述的主要意义在于，聚焦于（i）调节催产素系统的印记基因的影响，以及（ii）性拮抗等位基因对与疾病相关的性二态性表型的影响的数据收集，将为人类健康和基因组冲突的进化动态带来新的见解。
