The Fat Gene


By Richard J. Johnson /Peter Andrews R. J. ジョンソン /P. アンドリュース
English 日本語 日本語
In 1962 a human geneticist named James Neel proposed a hypothesis to solve a vexing evolutionary puzzle. What is now called type 2 diabetes—which he thought was caused by a single variant of some unidentified gene—can cause debilitating symptoms, including blindness, heart disease and kidney failure. It can also affect people in their reproductive years. In ancient humans, when no treatments were available, those features could have kept afflicted individuals from finding a mate, having children and passing the disease-causing gene down to future generations. In other words, natural selection should have eliminated the gene and, thus, the disease.  1962年,人類遺伝学者のニール(James Neel)は進化の理屈に反した不可解な謎を解く仮説を提唱した。あるタイプの糖尿病(現在では2型糖尿病と呼ばれる)は何らかの遺伝子のバリアント(変異タイプ)に原因があるとニールは考えた。糖尿病は失明や心疾患,腎不全などの症状を引き起こして身体を蝕む。生殖年齢で発病することもある。昔の人類には何の治療法もなく,この病気に苦しむ人たちはパートナーを見つけて子をもうける機会が少なくなって,病気の原因遺伝子は次世代に伝わりにくかったと考えられる。つまり,遺伝子ひいては病気は自然選択で排除されたはずだ。
Yet the disorder was common and growing more so. How could people with such a debilitating gene have survived, Neel wondered, and why was diabetes, which is defined by the presence of abnormally high levels of the sugar glucose in the blood, becoming more prevalent?  しかし糖尿病はありふれた病気となり,ますます増えている。なぜ身体を蝕む遺伝子を持つ人々が生き残ることができたのか。なぜ血糖値が異常に高くなる糖尿病が増えているのか。
Neel spent much of his time studying indigenous populations such as the Yanomami in the Amazon, who presumably had the same diabetes-related gene variant in their gene pool as other modern humans yet were almost never diabetic or fat. (Obesity increases risk for type 2 diabetes.) The contrast be­­tween native people and those in developed societies gave him an idea. In the distant past, he argued, there were most likely times when food was in short supply, causing hunger or even widespread famine. People with a gene variant that made their body particularly “efficient in the intake and/or utilization of food,” Neel wrote, would have socked away more of the scarce calories as fat. That extra fat would have given individuals with this so-called thrifty gene a survival edge in times of famine. In times of plenty, though, such as today, the same trait would lead to excessive weight gain and diabetes.  疑問を抱いたニールは多くの時間を費やし,アマゾンのヤノマミ族のような先住民族について調べた。先住民族も他の現代人と同様に糖尿病関連遺伝子のバリアントを遺伝子プール(集団中の遺伝子全体)に持っているはずだが,糖尿病や肥満になることはまずない(肥満は糖尿病のリスクを高める)。
The thrifty gene hypothesis has drawn criticism, but it has endured in one form or another for half a century. The idea that our body can be genetically programmed to store fat and that our rich modern diet and sedentary ways can send this program into overdrive has prompted a good deal of research into possible thrifty genes at the root of diabetes and other obesity-linked diseases: hypertension (high blood pressure), nonalcoholic fatty liver disease and heart disease. But critics of the hypothesis have argued that starvation in ancient humans happened too rarely and was over too quickly to select for genes that favor fat storage and that no definitive thrifty genes have been found.  倹約遺伝子説には反論も多かったが,形を変え半世紀を持ちこたえた。私たちの身体が脂肪を蓄えるよう遺伝的にプログラムされていて,現代の飽食と運動不足がそのプログラムを暴走させうるという考えから,糖尿病のほか高血圧や非アルコール性脂肪肝,心疾患といった肥満関連疾患の根底にある倹約遺伝子の研究が数多く行われた。
Recently, though, the two of us have looked deeper into our evolutionary past and found solid evidence confirming the essence of Neel’s hypothesis—that a mutation in a single gene made modern humans thrifty with calories. This mutation arose in ancient apes millions of years ago and in so doing, we think, enabled them to survive long periods of hunger. If we are correct, our hypothesis could also help reveal how those apes evolved into the earliest human ancestors, and it may pinpoint a gene that is behind many of the major diseases of modernity.  だが近年,私たち2人は人類の進化の歴史を詳細に調べ,ニール説の要を裏付ける確かな証拠を見いだした。わずか1つの遺伝子変異のせいで現代人がカロリーを倹約するようになったのだ。この変異は1000万年以上前の類人猿に生じたもので,これによって長期的な飢えを生き延びられるようになったと私たちは考えている。私たちが正しければ,この説は古代の類人猿が最初期の人類に進化するまでの道筋を明らかにするのに役立ち,多くの主要な現代病の原因遺伝子を突き止めることにもつながる可能性がある。