蛇到底会不会成精：决定蛇的性别的居然不是性染色体

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本文由尚恩“少一门”高考英语教研组整理编辑

对于人类而言，性染色体Y上的很多基因并不是特别重要。亦即，如果在遗传复制过程中丢失几个，也就丢了——所以Y染色体越来越短，这是被称为遗传衰变的过程。甚至，Y染色体本身丢失了，基因出问题的个体也能存活下来。

但现在，Daniel Winston Bellott在怀特海研究中心(Whitehead Institute)的David Page负责的实验室里进行了一项新研究，他发现将蛇的性染色体上的基因至关重要，并参与到关键的发育过程。

“事实证明，这些特定性染色体上的幸存基因可能在控制如何读取，解释和表达所有染色体上的所有基因方面起着非常重要的作用。”

在进化过程中，某些常染色体成了所谓的性染色体，不过具体演化过程还很神秘。

所以，Bellott认为蛇在研究中特别有用。“蛇的性染色体系统非常古老，很多基因都已在时间长河中丢失，所以还剩下的都是很重要的基因。”

为了了解有关染色体进化的更多信息，Bellott和Page首先收集了“祖先基因”列表，从不同的蛇类物种身上寻找共同的古老基因。

使Bellott惊讶的是，保留在蛇的特异性染色体上的基因与性别决定无关。他们在与性别相关的特定组织中表达的频率都不高。

相反，他们二人的研究确定了性染色体上的基因的3大关键特性。首先，性染色体上的基因必须对剂量敏感。换句话说，那些基因调控的蛋白质产物，多了或少了，蛇就会生病或死亡。其次，基因可能在不同组织中被广泛表达，而不是局限于一个特定的器官或区域。第三，现存基因都是负面选择的。简而言之，这意味着如果这些基因之一出了问题，那条蛇存活或产生后代的机会就很小。

当Bellott深入研究时，他发现对于许多基因来说，人类中的同等基因在诸如面部形成等关键发育过程中发挥了作用。

他说，以后的科学家们将能够通过基因预测发育障碍。“从某种意义上讲，我们对于蛇的研究等于是开了头，然后，通过研究蛇和禽鸟的Y染色体基因，可能找出更多的现今无法解释的人类先天缺陷的真凶。”

完结

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英文原文：

Sex-specific chromosomes are a dangerous place to be, if you're a gene. Because these chromosomes—Y chromosomes, in humans—do not have a matching chromosome with which to exchange genetic information, they are prone to losing non-essential genes left and right in a process called genetic decay.

Now, a new study from research scientist Daniel Winston Bellott in the lab of Whitehead Institute Member David Page broadens our understanding of what makes a gene able to survive on a sex-specific chromosome by looking at one especially slithery branch of the evolutionary tree: snakes.

Comparing surviving genes on snake sex-specific chromosomes to those that are lost to the ravages of time can teach scientists about the evolutionary pressures that shaped sex chromosomes as we know them today. "You might think, 'These are sex chromosomes, so the surviving genes should have something to do with sex, right?'" Bellott said. "But they don't."

Instead, many of these genes are essential to the survival of the animal, and take part in key developmental processes. "It turns out that these survivor genes on sex-specific chromosomes may play a very big role in governing how all of the genes across all the chromosomes are read, interpreted and expressed," said Page, who is also a professor of biology at Massachusetts Institute of Technology (MIT) and an Investigator of the Howard Hughes Medical Institute. "Winston's study is absolutely foundational to our understanding of what the sex chromosomes are, how the two sexes come to be, and how health and disease traits play out similarly or differently in males and females."

What is a sex chromosome, anyway?

Over the course of evolution, all sex chromosomes start out as regular, matching chromosomes called autosomes. Then, somewhere along the line, a mutation happens, and one of the chromosomes gains a "switch," that, when present, causes an embryo to to develop as a specific sex. "It's actually really easy to make a sex chromosome," said Bellott. "In most cases, you only need to change one or two genes and you've started the sex chromosome system."

This process has happened numerous times during the course of evolution. It makes sense; sexual reproduction is an efficient way to ensure genetic diversity. But the whole thing is a bit mysterious; are, for example, certain chromosomes predisposed to become sex chromosomes?

That's where Bellott thought snakes could be especially helpful. "Snakes have a relatively old system of sex chromosomes, where you have a lot of time for the chromosomes to diverge," Bellott said. "Time has swept away all the genes that aren't important, and you can see what kind of genes are left."

Their sex chromosome system also evolved from different autosomes, some 100 million years after humans', and thus would provide a useful vantage point from which to consider our own genomes.

To learn more about the evolution of these chromosomes, Bellott and Page first gathered a list of "ancestral genes," which were likely on the chromosome from which the snake sex chromosomes evolved. New sequencing data for several species of animals distantly related to snakes meant that they had a more complete list of these genes—1,648 to be exact.

Bellott began painstakingly sifting through the genes that remained on the sex-specific chromosomes of three species of snake: the pygmy rattlesnake, mountain garter snake, and the five-pacer viper. He eventually identified 103 ancestral genes that had survived as long as 90 million years of evolution on the snakes' sex chromosomes. With this list in hand, Bellott could then ask what these surviving genes had in common that set them apart from the hundreds of genes that were swept off the snakes' sex chromosomes by genetic decay.

What makes a survivor?

To Bellott's surprise, the genes that remained on the snakes' sex-specific chromosome had nothing to do with sex determination; neither were they expressed more often in sex-specific tissues, or more often in one sex than the other.

Instead, Bellott and Page's research identified three key properties that led to a gene's survival on snake sex-specific chromosomes. First, the gene must be dosage sensitive. In other words, the snake's body depends on its cells to produce an exact amount of that gene's protein product. Any more, or any less, and the snake experiences illness or death. Second, a surviving gene is likely broadly expressed in different tissues across the body, not localized to one specific organ or area. And third, surviving genes are subject to strong purifying, or negative, selection. Simply put, this means that if something goes wrong with one of these genes, the snake has a slim chance of survival or producing offspring.

When Bellott dove deeper into the genes' function, he discovered that for many of them the equivalent gene in humans played a role in key developmental processes such as the formation of the face. When these genes were mutated in humans, their faces—and other essential parts of the body—would not develop properly. "What Winston is seeing here is that the genes that were preserved on the sex specific chromosomes in snakes are disproportionately involved in birth defects in people," Page said. "We think that nature is selecting for the survival of [sex chromosome] genes whose dosage in certain parts of embryonic development is especially critical."

In time, Bellott said, this may allow scientists to predict genes whose role in developmental disorders is yet to be discovered. "In some sense, you get to the place where you're starting to work the experiment backwards in your mind, and say, 'Let's take the set of genes that are on sex specific chromosomes in snakes and birds, but that have not yet been implicated in birth defects in humans,'" Page said. "They might be prime candidates to be responsible for heretofore unexplained birth defects."

From snakes to humans

Next, the researchers sought to broaden their scope. They compared ancestral genes across the three species of snakes and 38 species of birds and mammals with a larger pool of genes that made it to the present day. Many of the surviving genes on bird and mammal chromosomes had different functions than those on snake chromosomes, but again, most had little to do with sex determination.

"Adding the snakes in with the birds and the mammals gave Winston enough data points to be able to see further and to see more precisely, and now for the first time, he was able to confirm something that we had been suspecting for a long time but really didn't have sufficient data to pin down," Page said. "And that is that the chromosomes that became sex chromosomes were not sort of inclined to function in sex differences. Before they got picked out of the crowd, they weren't specialized towards differentiating between the sexes in much of any way."

Then, as genes were lost over time, evolutionary pressures ensured that the same sort of genes survived. This idea that sex chromosomes—besides their key developental switch—have little do do with sex determination challenges the common notion of what a sex chromosome actually is.

"I hope people will pick up on this idea that the chromosomes that became sex chromosomes weren't in any way preordained," Page said. "They were just ordinary chromosomes out for a walk in the park, and something happened."

In the future, Bellott and Page plan to further broaden their scope to include other animals, toward the ultimate goal of understanding our own sex chromosomes. "We take these results, and we turn them into a lens through which we look at sex differences in health and disease in our own species," Page said. "This research really refines our ideas about what it means to be a gene on the human X or Y chromosome, and how we should think about those genes that survive."