手是如何進化的？答案就在你的背後。 (2/2)

Recently the New York Times picked up the following:

How Did Hands Evolve? The Answer Is Behind You. (2/2)

The evolutionary blueprint for hands was borrowed in part from a much older genetic plan for our nether regions, a new study suggests.

By Carl Zimmer – Origins

17 Sept. 2025

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Dr. Hintermann, who took over the project while working in the Geneva lab, grew zebrafish embryos from which she had removed the 5DOM locks, using CRISPR. If the locks were important in the development of fish fins, then deleting them might reveal how.

To her surprise, deleting 5DOM had little effect on the developing fins. But it disrupted a region on the underside of the zebrafish’s tail, where there are two openings: the anus, and a hole for the bladder and for sexual organs.

This surprise prompted the researchers to take a closer look at the same region in mouse embryos. Here they got a second surprise: 5DOM unlocks the genes that built that region in mammals, too.

These and other experiments led the scientists to a new hypothesis for the evolution of fingers and toes. The story starts a half-billion years ago, with the earliest, simplest fish. Their bodies were little more than heads connected to long-ribbon-like bodies; they swallowed food, which made its way down a long digestive tract until the remnants escaped through the anus. A nearby opening was used for sex, and the release of urine.

The embryos of this protofish unlocked different genes to create the different parts of its body. At the far end, 5DOM unlocked the genes for the anus as well as the opening for its urethra and sexual organs.

That genetic recipe hasn’t changed in a half-billion years. That’s why 5DOM still controls the development of that region in both zebrafish and mice — and us.

But about 360 million years ago, the scientists propose, 5DOM underwent an evolutionary change. Now it could build not only our nether regions but our fingers and toes, too.

M. Brent Hawkins, an evolutionary biologist at Harvard and an author of the study, compared the recycling of 5DOM to songs being recycled by musicians. “It’s like Jay-Z being inspired by old show tunes and sampling ‘It’s the Hard Knock Life,’” he said.

Hands and nether parts might seem to have little in common, but there are some key similarities. For one thing, both are extremities: In early fish, 5DOM unlocked genes that determined the anatomy at the far end of the body. In a developing limb, the fingers and toes develop at the far end, too.

But Neil Shubin, an evolutionary biologist at the University of Chicago and another author of the study, said that the precise evolutionary changes that had given 5DOM its new job remain a mystery.

“It caught us off guard,” he said. “We have some homework to do to figure out how it happened.”

Translation

手是如何進化的？答案就在你的背後。 (2/2)

一項新研究表明，手的演化藍圖部分借鑒了我們更古老的生殖器官的基因排序藍圖。

（繼續）

在日內瓦實驗室工作期間接手該計畫的欣特曼博士利用CRISPR技術，對斑馬魚胚胎進行了改造，並移除了其中的5DOM鎖。如果這些鎖在魚鰭發育中起著重要作用，那麼刪除它們或許能揭示其作用機制。

令她驚訝的是，刪除5DOM對魚鰭的發育幾乎沒有影響。但它破壞了斑馬魚尾部腹側的一個區域，該區域有兩個開口：肛門，以及膀胱和性器官的開口。

這項意外發現促使研究人員對小鼠胚胎的同一區域進行了更深入的研究。他們在這裡得到了第二個驚喜：5DOM 也能把哺乳動物中建構該區域的基因解鎖。

這些實驗以及其他實驗使科學家提出了關於手指和腳趾進化的新假說。故事始於五億年前，最早、最簡單的魚類。它們的身體幾乎只有頭部和長帶狀的身體；它們吞食食物，食物沿著長長的消化道向下移動，最終殘餘物從肛門排出。在附近的開口用於交配和排尿。

這種原始魚的胚胎活化了不同的基因，從而形成了身體的不同部位。在末端，5DOM 解鎖了肛門以及尿道和性器官開口的基因。

這套基因序列在五億年間從未改變。這就是為什麼 5DOM 至今仍然控制著斑馬魚、老鼠以及我們人類該區域的發育。

但科學家推測，大約3.6億年前，5DOM發生了演化上的改變。如今，它不僅能建造我們的生殖器官，還能建造我們的手指和腳趾。

哈佛大學進化生物學家、該研究的作者之一M. Brent Hawkins 將5DOM的循環利用比喻為音樂家對歌曲的循環利用。 他說:「這就像Jay-Z從老歌舞劇中汲取靈感，並採樣了《It's the Hard Knock Life》這首歌一樣」。

手和生殖器官看似沒什麼共同之處，但其實卻有一些關鍵的相似之處。首先，它們都是肢體末端：在早期魚類中，5DOM解鎖了決定身體末端解剖結構的基因。在發育中的肢體中，手指和腳趾也是在末端發育的。

但芝加哥大學演化生物學家、這個研究的另一位作者Neil Shubin表示，究竟是什麼演化改變賦予了5DOM新的工作，至今仍是個謎。

他說:“這讓我們措手不及”; “我們有功課去做, 要好好調查一下事情是怎麼發生的。”

So, millions of years ago, our fishy ancestors moved from water to land. Along the way, their fins turned into feet, with toes. And hundreds of millions of years later, the front pair evolved into hands. Now the precise DNA-editing technology has enabled scientists to reconstruct this ancient evolutionary change. It turns out that hands and feet were not the products of new genes doing new things. Rather, through natural selection, pieces of old genetic recipes for ancient body parts were cobbled together into new combinations. The researchers find that 5DOM is responsible to unlock the genes for the anus as well as the opening for its urethra and sexual organs. Apparently, it is an interesting discovery that may help us to know how and where we come from.