When the protein-encoding genes of the human are compared with the protein-encoding genes of the chimpanzee, they are about 99 percent the same. Moreover, the one percent that are distinctive aren't obviously interesting, being involved with such traits as sperm surface proteins and immune responses.
当将编码人类蛋白的基因与编码黑猩猩蛋白基因进行比较时，他们之间有99%的相似度。而且，涉及到诸如精子表面蛋白和免疫反应特征的1%的基因也没有引起明显的兴趣。
因此，考虑到这个，对于许多方面尤其是意识方面，人类和黑猩猩彼此不同的基因基础是什么呢？
A most ingenious approach to this question is being developed in the lab of Katherine Pollard at the University of California in San Francisco. To understand their experiments, we first need a crash course in genes and embryos. I'll try to make it quick.
在旧金山加利福尼亚大学Katherine Pollard 实验室设计了一个非常有创意的方法。为了理解他们的试验，我们首先需要一堂在基因和胚胎方面的速成课，我将试着很快对此作一阐述。
Our single-celled ancestors who lived more than 1.5 billion years ago were already impressively gene-rich and sophisticated, as per last week's blog. Notably, their genomes encoded a rich toolkit of regulatory molecules that turn on or off the expression of genes as appropriate to the occasion. For example, in the presence of bacterial food, the ancient ancestors turned on the expression of genes that allowed them to crawl around and engulf their prey. When things got lean, they instead turned on genes that allowed them to swim off to find new food sources.
生活在15亿年前的单细胞生物祖先就已经拥有丰富而复杂的基因，根据上周的博客。值得注意的是，他们的基因组编码了一个丰富的工具箱，这个工具箱由可控分子构成，这些分子可以根据合适的情况打开或关闭基因的表达。例如，有细菌性食物时，古代的祖先会打开基因的表达，这些基因允许他们爬过去并且吞噬他们的捕食。相反，当食物贫乏时，他们会打开让他们游过去找到新的食物来源的基因。
The way these switches work is pretty straightforward to explain, albeit exquisitely intricate in detail. Basically, proteins are encoded by sectors of DNA called genes. Contiguous to each gene is DNA that doesn't code for protein; instead, it functions as the gene's on-off switch. When regulatory molecules bind to this switch DNA, the contiguous gene is either expressed or prevented from being expressed. So, very crudely, the thing on the wall is the switch DNA, your finger is the regulator, and gene expression is the light turning on or turning off.
这些开关的工作方式能够被非常直接明了地解释，细节上虽然精巧复杂。基本上，蛋白质被称之为基因的DNA编码。每个相邻基因之间是不能编码蛋白质的DNA；相反，它起着基因启动－关闭开关的功能。当调控分子与这个开关DNA结合时，相邻的基因便开始表达或终止表达。因此，大体上可以这么形容，在墙上的东西就是开关DNA，手指是调控器，基因表达就是打开灯或关闭灯。
The common-ancestral selves were unicellular, whereas the animal lineage has elected to construct multicellular selves. In making this transition, animals hung on to the same switch arrangement and the same sets of regulators used by the ancestors, but they added a splendid additional idea. In addition to being responsive to signals from the environment, they also became responsive to signals coming from their very own cells. So, to highly oversimplify the situation, after a fertilized egg has divided into two and then four, then eight, then 16 cells (where the human has, gulp, ten trillion cells), cell #16 makes a regulator that acts to switch on a set of unique genes in cell #10, the outcome being that cell #10 and its progeny eventually give rise to nervous tissue. Meanwhile, cell #11 expresses a different suite of genes, poising its progeny to influence yet other cells to differentiate into muscle.
祖先本身是单细胞的，然而动物进化成多细胞。在这个变化过程中，动物继续选择祖先使用开关排列和调控器，但是他们加入了一个非常好的创意。除了对环境的信息作出反应，他们也可以对来自自身的细胞的信号作出反应。因此，为了是这种情况更加简化，一个受精卵变成2个、4个、8个，16个（人类有10万亿个细胞），#16 细胞变成一个控制器，负责打开#10细胞的独特基因，结果是#10细胞和它的子代们最终产生了神经组织。同时，#11细胞表达另一套不同的基因，平衡它的子代影响其它细胞分化成肌肉。
As animals, and hence animal embryos, complexified over time, these cell-to-cell interactions have become increasingly impressive. In the developing mammalian brain, for example, neurons migrate up into the cranium, using much the same kind of amoeboid movement that our deep ancestor employed to capture bacteria. Neurons that reach a particular destination switch on genes that allow them to secrete a nerve growth hormone. As the next phalanx of neurons migrates into the region, they follow the hormone gradient, akin to male moths moving up pheromone gradients to find females, avidly competing for hormones that will enable their proliferation. The first to arrive at the pulsating source proceed to form synaptic connections with their targets; any laggards, by contrast, fail to proliferate and instead degenerate.
由于动物和动物胚胎随着时间变得更加复杂了，这些细胞和细胞之间的相互作用也越来越让人印象深刻。例如，在进化中哺乳动物的大脑，神经迁入到了头颅，用我们祖先使用过的变形运动来捕捉细菌。达到特殊部位的神经元可以打开让他们分泌神经生长激素的基因。随着神经元跟随着激素的浓度，大量进入这个部位，同雄蛾向着激素的方向移动寻找雌飞蛾一样，争夺着能使它们繁殖的激素。首先到达脉冲源的神经元就会和他们的靶点形成突触结合，相比之下，落后者不是繁殖而是退化。
Granted that this is an absurdly simplified account of brain development, it suffices to make a key point, which is that brains build themselves. Bottom up. When A happens, that allows B and C to happen; B allows D and E to happen; and so on.
假设这是一个荒谬的脑部发展的简化描述，它可以成为一个关键点，也就是说大脑建立自己。自下而上的。当A发生的时候，允许B和C发生；B允许D、E发生，等等。
Because brain development is so contingent on what has gone on before, it's pretty easy to alter what happens. For example, if the pioneer neurons in our example carried a switch mutation that prevented them from secreting the nerve growth hormone at the appropriate time, the next phalanx of neurons wouldn't move towards them and might, instead, pick up on a more distant hormonal signal from another brain region and move in that direction, forming synapses with a new set of neurons altogether. A brain is still constructed, but it will have different kinds of neural pathways and connections and hence, perhaps, different ways of doing things.
由于大脑的进化是根据之前所发生决定的，也很容易改变所发生的。例如，假如先前的神经元发生突变阻碍它们在合适的时间分泌神经生长激素，大量的神经元便不会朝着它们移动，相反，有可能从另一个大脑区选择一个更远的激素信号，朝着另外一个方向移动，和一组新的神经元形成突触。大脑仍然被建造，仍然拥有不同的神经路线和连接方式，因此，可能有不同种做事情的方法。
So now we can return to the chimp-human question. If the chimp and human protein-encoding genes are virtually all the same, then are there any interesting differences in their switch regions? Given the bottom-up nature of development, mutant switches could have large-scale consequences.
到现在为止，我们返回到黑猩猩－人类的问题上。假如黑猩猩和人类的编码蛋白的基因一样，那么在开关区间有什么有趣的不同之处呢？考虑到自上而下的发展本质，突变开关能产生大规模的结果。
开关序列的鉴别要比基因的鉴别计算起来更具有挑战性，但是Pollard 实验室对此进行了研究。
开关序列的鉴别要比基因的鉴别计算起来更具有挑战性，但是Pollard 实验室对此进行了研究。
Basically, they compare the DNA sequences adjacent to genes that are found not only in humans and chimps but also in mice and rats, where the most recent common ancestor of these four mammals roamed the planet some 60 million years ago.
基本上，他们比较了与基因相邻的DNA序列，这些基因不仅能在人类和黑猩猩身上找到，而且在大鼠和小鼠身上也可以找到，而且60万年前生活在这个星球的四种哺乳动物最近的共同祖先就拥有这个序列。
The Pollard logic is this:
Pollard 的逻辑是这样的：
1) If a given set of sequences isn't doing anything important, which is usually the case, then the rat, mouse, human, and chimp versions are expected to be very different from one another. That's because they aren't under selection, so they tend to accumulate mutations. In genomic lingo, the sequences are said to "drift."
假如一系列既定的序列不发挥任何重要作用，通常也是这样的情况，那么大鼠、小鼠、人类和黑猩猩彼此就会差别很大。那是由于他们没有进行选择，因此他们易于积累突变。用基因组术语，这个序列称之为“漂移”。
2) By contrast, if the sequences function as switches, then they are expected to be very similar because they are under selection to maintain their gene-regulating function.
相比之下，假如序列执行开关的职能，那么它们会非常相似，因为它们经过选择保持他们的基因调控功能。
3) Of particular interest are cases where the mouse, rat, and chimp sequences are all identical, indicating intense selection to maintain them, whereas the human sequence is markedly different from the other three. The Pollard lab has thus far identified 202 such cases, where each is called a human accelerated regions or HAR.
特别有趣的是大鼠、小鼠和黑猩猩的序列是一样的，表明是经过挑选来维持的，然而人类的序列与这三类有着显著的差别。Pollard 实验室到目前为止确定202种这样的情况，每个被称为人类加速地区或HAR.
Now the fun begins. A researcher picks out a HAR (e.g. HAR34), figures out what gene it's contiguous to, and then asks: Where and when is that gene switched on/off during embryological development? And then: Is its expression pattern different in the human than in mouse, rat, or chimp? If it is, then the novel pattern may prove to be relevant to an understanding of how humans are distinctive creatures.
现在兴致来了。一位研究员挑出一个HAR，指出它与什么基因相连，然后问：在胚胎发育期基因是何时何地被打开或关闭？然后问：它的表达方式在人类和在大鼠、小鼠或黑猩猩体内有差别吗？假如有，新的方式可以证明与理解人类是独特的物种的原因有关。
Thus far there are three preliminary stories relevant to the brain. HAR1 proves to mark a genetic region that is expressed early in the development of the neocortex; HAR152 is near the gene encoding a protein called neurogenin-2 that is expressed in a region of the hippocampus with a central role in learning and memory; and HAR2 is near a gene with strong expression in the hand, perhaps playing some role in human-specific hand coordination.
到现在为止有三个与大脑有关的表述。HAR1证明了标码在大脑皮质形成过程中早期表达的基因区；HAR152 靠近编码蛋白基因，称之为神经元配基－2，神经元配基－2在海马区表达，在学习和记忆分面扮演着重要的角色；HAR2靠近在手上有强表达的基因，在人类特有的手协调方面发挥着某些功能。
The knee-jerk response to this account is to think "Aha — maybe some of those novel HAR sequences are running some new human-specific brain module or widget! Like my consciousness!"
对于这个数据下意识的反应就是思考“或许一些新的HAR序列正运行着某些人类所特有的新的大脑模式或部件，就像意识一样！”
But if we circle back to our core notion, that brains build themselves, and think about the HARs in this context, then we realize that we're not likely to be talking about new modules or widgets. Just as in our hypothetical example, where a group of neurons failed to secrete a hormone and the second phalanx of neurons wandered off to find new targets, a mutant HAR is more likely to result in some human-specific pattern of regional brain differentiation. Indeed, going back to the finch-song domesticated-ape story told here and here, some of the mutant HARs may have the effect of releasing constraints on ape-brain organization, opening things up to greater novelty and plasticity
但是假如我们返回到核心观念，即大脑可以自我组建，在这个背景下思考HARs，那是我们便会意识到我们不可能谈论新的模式或是部件。就像我们假设的例子一样，神经元没有分泌激素并且大量神经元没有找到新的靶点，突变的HAR更可能导致人类特有的大脑区域差别模式。的确，返回到这里所讲的驯养的猩猩，一些突变的HARs可能对猩猩大脑的组织产生抑制，开启更新具有更大可塑性的东西。
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