Cockroaches scurry around with thousands of pieces of bacterial genomes
Cockroaches scurry around with thousands of pieces of bacterial genomes
蟑螂体内携带数千段细菌基因组
Last week, we looked at a new study of the origin of complex cells, one that showed that our ancestors’ genomes were pieced together from bits and pieces of multiple species. It put a spotlight on a phenomenon called horizontal gene transfer, in which a gene from one species is incorporated into the genome of a distantly related species. The frequency of horizontal gene transfer means that, in addition to the neatly branching trees that relate species by common descent, there are small threads connecting distant branches of the tree of life.
上周，我们探讨了一项关于复杂细胞起源的新研究，该研究表明我们祖先的基因组是由多个物种的碎片拼凑而成的。这凸显了一种被称为“水平基因转移”（horizontal gene transfer）的现象，即一个物种的基因被整合到亲缘关系较远的另一个物种的基因组中。水平基因转移的频繁发生意味着，除了通过共同祖先联系起来的整齐分支树状图外，生命之树的遥远分支之间还存在着细小的连接线。
It’s easy to see why horizontal gene transfer would be common among microbes. They often live in complex communities that are likely awash in the DNA of dead and damaged cells. Plus, bacteria and archaea lack a membrane between their DNA and the rest of the cell, making it easier for environmental DNA to find its way to the genome. However, a new study this week shows that horizontal gene transfers are remarkably common even in multicellular animals. And it does so by examining the genomes of multiple cockroach species, which have had bits of bacterial DNA for millions of years.
不难理解为什么水平基因转移在微生物中很常见。它们通常生活在复杂的群落中，周围很可能充斥着死亡和受损细胞的 DNA。此外，细菌和古菌的 DNA 与细胞其余部分之间缺乏核膜，这使得环境中的 DNA 更容易进入基因组。然而，本周的一项新研究表明，即使在多细胞动物中，水平基因转移也异常普遍。该研究通过检查多种蟑螂的基因组证实了这一点，这些蟑螂在数百万年来一直携带者细菌 DNA 片段。
Going horizontal
水平转移的机制
Neither bacteria nor archaea keep their DNA in a structure like the nucleus. As a result, any DNA that finds its way inside the cell has the potential to become intermingled with the genome and be incorporated permanently. That permanent incorporation is often aided by the DNA damage repair enzymes, which sometimes “fix” damage by inserting any DNA they come across in a cell. Another reason horizontal gene transfer is a big factor among microbes is that they lack dedicated germ cells. If foreign DNA gets incorporated into the genome of any cell, it will be inherited by any descendants of that cell. In contrast, in multicellular animals, any foreign DNA incorporated into the genome of a liver cell will not be inherited by anything. So, you not only have to get the foreign DNA into the nucleus, but it also needs to get into the nucleus of the right cell.
细菌和古菌都没有像细胞核那样的结构来包裹 DNA。因此，任何进入细胞内部的 DNA 都有可能与基因组混合并被永久整合。这种永久整合通常由 DNA 损伤修复酶辅助，这些酶有时会通过插入在细胞中遇到的任何 DNA 来“修复”损伤。水平基因转移在微生物中成为重要因素的另一个原因是它们缺乏专门的生殖细胞。如果外源 DNA 被整合到任何细胞的基因组中，它就会被该细胞的所有后代继承。相比之下，在多细胞动物中，整合到肝细胞基因组中的任何外源 DNA 都不会被遗传给后代。因此，你不仅需要将外源 DNA 送入细胞核，还需要将其送入特定细胞（生殖细胞）的细胞核中。
Horizontal gene transfer in complex, multicellular animals was expected to be rare. When researchers started sequencing animal genomes, they found lots of bits of viruses scattered throughout most of them. But they didn’t find many pieces of bacterial DNA. That was partly because the software that assembled the genome from individual fragments of genome sequence was made to treat bacterial sequence as contamination. That is not unreasonable, given that we were typically growing up lots of copies of the animal DNA by placing it in bacteria. Since then, we’ve developed techniques that allow us to sequence DNA without growing lots of copies in bacteria. We’ve also got the ability to obtain sequence-extended fragments of DNA, sometimes many thousands of bases long. These “long read” DNA sequences will often cover both borders where the bacterial sequence meets the animal sequence, making clear that the bacterial version wasn’t the result of contamination.
人们曾认为，在复杂的、多细胞动物中，水平基因转移是罕见的。当研究人员开始对动物基因组进行测序时，他们在大多数基因组中发现了散布的许多病毒片段，但并没有发现多少细菌 DNA 片段。这部分是因为用于从基因组序列碎片中组装基因组的软件，被设定为将细菌序列视为污染。考虑到我们通常通过将动物 DNA 置于细菌中来扩增其拷贝，这种做法并非不合理。自那时起，我们开发了无需在细菌中扩增即可对 DNA 进行测序的技术。我们还获得了获取长片段 DNA 序列的能力，有时长达数千个碱基。这些“长读长”（long read）DNA 序列通常能覆盖细菌序列与动物序列交界的两个边界，从而明确证明这些细菌序列并非污染所致。
Over time, it has become clear that dozens of animal genes have originated from horizontal gene transfer—including a number in our own genome. And that’s just genes. If you consider areas of the genome that don’t encode genes, the contribution from other species gets considerably larger.
随着时间的推移，人们逐渐清楚，数十个动物基因起源于水平基因转移——包括我们人类基因组中的一些基因。这还仅仅是基因层面。如果考虑到基因组中不编码基因的区域，来自其他物种的贡献则会大得多。
Lots of DNA, little impact
大量 DNA，微小影响
A team decided to gain perspective by making a comprehensive list of horizontally transferred DNA found in a group of related animal species. They chose cockroaches, and they had a good reason. Cockroaches are closely related to termites. Termites don’t get a lot of nitrogen in their diet of wood, which is largely comprised of a polymer of sugar molecules. To make up for that, they rely on endosymbiotic bacteria called Blattabacterium that reside inside the termite’s body, and are very efficient at recycling the nitrogen that would be excreted as waste in other species. While the roaches’ diets have diversified considerably, they’ve held on to the Blattabacterium. Since these bacteria live inside the animals’ bodies and are transferred to ensuing generations by being placed in their eggs, there are plenty of opportunities for horizontal gene transfer.
一个研究团队决定通过列出一组相关动物物种中发现的水平转移 DNA 的综合清单来获得更全面的视角。他们选择了蟑螂，并且理由充分。蟑螂与白蚁亲缘关系密切。白蚁以木材为食，木材主要由糖分子聚合物组成，因此白蚁无法从饮食中获得足够的氮。为了弥补这一点，它们依赖于居住在体内的内共生细菌——布拉特氏菌（Blattabacterium），这种细菌能非常高效地回收在其他物种中会被当作废物排出的氮。虽然蟑螂的饮食结构已经发生了巨大的多样化，但它们依然保留了布拉特氏菌。由于这些细菌生活在动物体内，并通过进入卵细胞传递给下一代，因此存在大量的水平基因转移机会。
Indeed, there is a lot of Blattabacterium DNA in cockroach species. Setting a minimum length of 50 bases long, the team found anywhere from a low of 93 instances of bacterial sequence to a high of 4,900, depending on the roach species. Most of these were short—the median size was just 160 bases long. Depending on the species, 75 percent or more were outside of regions that encode genes. Some of the inserts seem to have been around since the origin of the cockroach lineage, and others are shared among closely related species, suggesting that they originated more recently. It’s clear that most of these sequences aren’t really doing anything useful for the roaches—they got there by accident and simply don’t do enough damage for evolution to get rid of them. But their frequency suggests that horizontal gene transfer is a fairly regular occurrence, at least on evolutionary timescales. So, it’s possible that horizontal gene transfer may play a larger role as a source of diversity in the genomes of animals than we’ve appreciated.
事实上，蟑螂体内确实存在大量的布拉特氏菌 DNA。研究团队设定了 50 个碱基的最小长度，发现不同种类的蟑螂体内细菌序列片段的数量从 93 段到 4,900 段不等。其中大多数都很短——中位数长度仅为 160 个碱基。根据物种的不同，75% 或更多的片段位于基因编码区之外。一些插入片段似乎自蟑螂谱系起源以来就一直存在，而另一些则在亲缘关系相近的物种间共有，这表明它们起源的时间较晚。显而易见，这些序列中的大多数对蟑螂并没有什么实际用途——它们是偶然进入的，且并未造成足够的损害以至于进化需要将其剔除。但它们的出现频率表明，至少在进化时间尺度上，水平基因转移是一种相当普遍的现象。因此，水平基因转移作为动物基因组多样性的来源，其作用可能比我们之前所认识到的要大得多。