The role of thrifty genes in the origin of alcoholism: A narrative review and hypothesis.
The role of thrifty genes in the origin of alcoholism: A narrative review and hypothesis.
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DOI：
10.1111/acer.14655
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Johnson RJ
中科院分区：
文献类型：
--
作者：
Carn D;Lanaspa MA;Benner SA;Andrews P;Dudley R;Andres-Hernando A;Tolan DR;Johnson RJ
在这篇叙述性综述中，我们提出了一个假设，即发生在1500万年和1000万年前的两个基因的关键突变，在饥饿时期对祖先人类是单独的，然后是集体的适应性，但在现代文明中是不适应的（即，“节俭基因”），其结果是，这些基因不仅增加了我们今天肥胖的风险，而且增加了酗酒的风险。这两种突变都发生在祖先猿类在深刻的气候变化或环境动荡期间经历水果供应丧失的时候。1500万年前尿酸酶（尿酸氧化酶）活性的沉默通过增加存在于逐渐减少的水果中的果糖作为脂肪储存的能力来提高生存率，这是果糖代谢过程中尿酸产生增加的结果，刺激脂肪生成并阻止脂肪酸氧化。同样，大约1000万年前，IV类乙醇脱氢酶（ADH 4）的突变导致乙醇氧化能力显著增加了40倍，这使得我们的祖先能够摄取掉落的发酵水果。反过来，摄入的乙醇可以激活醛糖还原酶，刺激葡萄糖转化为果糖，而乙醇代谢过程中产生的尿酸可以进一步增强果糖的产生和代谢。通过帮助生存，这些突变将使我们的祖先能够产生更多的脂肪，主要来自果糖，以适应中新世中期的破坏和东非中新世晚期的干旱化。不幸的是，代谢和利用乙醇的能力增强现在可能会增加我们酗酒的风险，这可能是曾经适应性节俭基因的另一个后果。
In this narrative review, we present the hypothesis that key mutations in two genes, occurring 15 and 10 million years ago, were individually and then collectively adaptive for ancestral humans during periods of starvation, but are maladaptive in modern civilization (i.e., “thrifty genes”), with the consequence that these genes not only increase our risk today for obesity, but also for alcoholism. Both mutations occurred when ancestral apes were experiencing loss of fruit availability during periods of profound climate change or environmental upheaval. The silencing of uricase (urate oxidase) activity 15 million years ago enhanced survival by increasing the ability for fructose present in dwindling fruit to be stored as fat, which was a consequence of enhanced uric acid production during fructose metabolism that stimulated lipogenesis and blocked fatty acid oxidation. Likewise, a mutation in class IV alcohol dehydrogenase (ADH4) ~10 million years ago resulted in a remarkable 40-fold increase in the capacity to oxidize ethanol, which allowed our ancestors to ingest fallen, fermenting fruit. In turn, the ethanol ingested could activate aldose reductase that stimulates the conversion of glucose to fructose, while uric acid produced during ethanol metabolism could further enhance fructose production and metabolism. By aiding survival, these mutations would have allowed our ancestors to generate more fat, primarily from fructose, to survive changing habitats due to the Middle Miocene disruption and also during the late-Miocene aridification of East Africa. Unfortunately, the enhanced ability to metabolize and utilize ethanol may now be acting to increase our risk for alcoholism, which may be yet another consequence of once-adaptive thrifty genes.
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DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
DOI：
10.1099/13500872-142-6-1399
发表时间：
1996-06-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
deJongGubbels, P;vanDijken, JP;Pronk, JT
通讯作者：
Pronk, JT
影响因子：
7.7
作者：
Gray SM;Meijer RI;Barrett EJ
通讯作者：
Barrett EJ
影响因子：
1.8
作者：
Dietrich, Oliver;Heun, Manfred;Zarnkow, Martin
通讯作者：
Zarnkow, Martin
影响因子：
2.5
作者：
Ehlers, Cindy L.;Wilhelmsen, Kirk C.
通讯作者：
Wilhelmsen, Kirk C.