Jasienska Grazyna, Ellison Peter T, Galbarczyk Andrzej, Jasienski Michal, Kalemba-Drozdz Malgorzata, Kapiszewska Maria, Nenko Ilona, Thune Inger, Ziomkiewicz Anna
Department of Environmental Health, Jagiellonian University Medical College, Krakow, Poland
Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Proc Biol Sci. 2015 Mar 22;282(1803):20142395. doi: 10.1098/rspb.2014.2395.
The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.
那些对健康有害的等位基因，尤其是在老年时，被认为在人群中持续存在是因为它们也为个体带来一些益处（通过拮抗性多效性）。载脂蛋白E（ApoE）基因座上的ApoE4等位基因，编码载脂蛋白E（ApoE），显著增加了健康状况不佳的风险，但它在许多人群中的频率相对较高。为什么它没有被对健康有益的ApoE3等位基因通过自然选择所取代呢？ApoE是卵巢雌激素和孕酮产生所需胆固醇前体的主要供应者，因此ApoE被认为是可能导致生殖性能差异的潜在候选基因。我们的结果支持这一假设，表明在117名月经规律的女性中，那些至少有一个ApoE4等位基因的基因型女性的平均黄体期孕酮水平（144.21 pmol l(-1)）显著高于没有ApoE4的基因型女性（120.49 pmol l(-1)），这表明其生育潜力更高。激素水平基于整个月经周期的每日数据。我们认为，在携带ApoE4等位基因的女性中发现较高的孕酮水平，可能为人类群体中维持具有祖先特征且对健康有害的ApoE4等位基因的进化机制提供首个有力证据。
