Speakman John R
School of Biological Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.
Diab Vasc Dis Res. 2006 May;3(1):7-11. doi: 10.3132/dvdr.2006.010.
Over the last 50 years there has been a major epidemic of obesity and associated co-morbidities, the so-called 'metabolic syndrome', mostly in the western world but with an increasingly global dimension. The development of such chronic diseases has a strong genetic component, yet the timescale of their increase cannot reflect a population genetic change. Consequently, the most accepted model is that obesity and its sequelae are a result of a gene-environment interaction, an ancient genetic selection to deposit fat efficiently that is maladaptive in modern society. Why we have this genetic predisposition has been a matter of much speculation. Following the seminal contribution of Neel, there has been a broad consensus that over evolutionary time we have been exposed to regular periods of famine, during which fatter individuals would have enjoyed a selective advantage by their greater survival. Consequently, individuals with genes promoting the efficient deposition of fat during periods between famines ('thrifty genes') would be favoured. In the modern environment this genetic predisposition prepares us for a famine that never comes, and an epidemic of obesity with all the attendant chronic illnesses follows. In this review I present details of the evidence supporting the famine hypothesis and then show that this idea has five fundamental flaws. In essence, famines are a relatively modern phenomenon and occur only about once every 100-150 years. Consequently, most human populations have only experienced at most 100 famine events in their evolutionary history. Famines involve increases in total mortality that only rarely exceed 10% of the population. Moreover, most people in famines die of disease rather than starvation and the age distribution of mortality during famine would not result in differential mortality between lean and obese individuals. A simple genetic model shows that famines provide insufficient selective advantage over an insufficient time period for a thrifty gene to have any penetration in the modern human population. Over the 40 or so years since Neel proposed the thrifty gene hypothesis, no convincing candidates for these genes have been discovered. My analysis suggests that perhaps it is time to call off the search.
在过去50年里，肥胖及相关合并症（即所谓的“代谢综合征”）出现了大流行，主要发生在西方世界，但影响范围日益全球化。这类慢性病的发生有很强的遗传因素，但其增加的时间尺度并不能反映群体基因变化。因此，最被认可的模型是，肥胖及其后果是基因与环境相互作用的结果，是一种在现代社会中不适应的、有效储存脂肪的古老基因选择。我们为何有这种遗传易感性一直备受猜测。继尼尔的开创性贡献之后，人们已基本达成共识，即经过漫长的进化时间，我们曾经历过周期性的饥荒，在此期间，较胖的个体因存活率更高而具有选择优势。因此，那些在饥荒间隙期能促进脂肪有效储存的基因（“节俭基因”）的个体将受到青睐。在现代环境中，这种遗传易感性让我们为一场从未到来的饥荒做好了准备，随之而来的便是肥胖及所有相关慢性病的流行。在这篇综述中，我详述了支持饥荒假说的证据细节，然后指出这一观点存在五个根本缺陷。从本质上讲，饥荒是一种相对现代的现象，大约每100 - 150年才发生一次。因此，大多数人类群体在其进化史上最多只经历过100次饥荒事件。饥荒会导致总死亡率上升，但很少超过人口的10%。此外，饥荒中的大多数人死于疾病而非饥饿，而且饥荒期间死亡的年龄分布不会导致瘦人和胖人之间的死亡率差异。一个简单的遗传模型表明，饥荒在不足够长的时间内提供的选择优势不足以让节俭基因在现代人群中得以传播。自尼尔提出节俭基因假说以来的40多年里，尚未发现这些基因令人信服的候选基因。我的分析表明，或许是时候停止寻找了。
