Chakraborty Mahul, Fry James D
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Curr Biol. 2016 Jan 25;26(2):219-223. doi: 10.1016/j.cub.2015.11.049. Epub 2015 Dec 31.
Environmental heterogeneity is thought to be an important process maintaining genetic variation in populations [1-4]: if alternative alleles are favored in different environments, a stable polymorphism can be maintained [1, 5, 6]. This situation has been hypothesized to occur in genes encoding multi-substrate enzymes [7], in which changes that increase activity with one substrate typically decrease activity with others [8-10], but examples of polymorphisms maintained by this mechanism are rare. Here, we present evidence that a polymorphism in an enzyme gene in Drosophila melanogaster is maintained by such a trade-off. The mitochondrially localized aldehyde dehydrogenase in D. melanogaster has two important functions: detoxifying acetaldehyde derived from dietary ethanol [11] and detoxifying larger aldehydes produced as byproducts of oxidative phosphorylation [12]. A derived variant of the enzyme, Leu479Phe, is present in moderate frequencies in most temperate populations but is rare in more ethanol-averse tropical populations. Using purified recombinant protein, we show that the Leu-Phe substitution increases turnover rate of acetaldehyde but decreases turnover rate of larger aldehydes. Furthermore, using transgenic fly lines, we show that the substitution increases lifetime fitness on medium supplemented with an ecologically relevant ethanol concentration but decreases fitness on medium lacking ethanol. The strong, opposing selection pressures, coupled with documented highly variable ethanol concentrations in breeding sites of temperate populations, implicate an essential role for environmental heterogeneity in maintaining the polymorphism.
环境异质性被认为是维持种群遗传变异的一个重要过程[1 - 4]：如果不同等位基因在不同环境中受到青睐，那么稳定的多态性就可以得以维持[1, 5, 6]。据推测，这种情况会发生在编码多底物酶的基因中[7]，在这类基因中，增加对一种底物活性的变化通常会降低对其他底物的活性[8 - 10]，但通过这种机制维持的多态性实例却很罕见。在此，我们提供证据表明，果蝇中一个酶基因的多态性是通过这种权衡得以维持的。果蝇中定位于线粒体的醛脱氢酶有两个重要功能：解毒源自饮食中乙醇的乙醛[11]以及解毒作为氧化磷酸化副产物产生的较大醛类[12]。该酶的一个衍生变体Leu479Phe，在大多数温带种群中以中等频率存在，但在对乙醇更排斥的热带种群中却很罕见。通过使用纯化的重组蛋白，我们发现Leu - Phe替代增加了乙醛的周转速率，但降低了较大醛类的周转速率。此外，通过使用转基因果蝇品系，我们发现这种替代增加了在添加了与生态相关乙醇浓度的培养基上的寿命适应性，但降低了在缺乏乙醇的培养基上的适应性。强大且相反的选择压力，再加上有记录表明温带种群繁殖地的乙醇浓度高度可变，这表明环境异质性在维持这种多态性方面起着至关重要的作用。
