10 Biggest Puzzles of Human Evolution

NOBODY would mistake a human for a chimpanzee, yet we share more DNA than mice and rats do. How can that be? Advances in genomics are starting to unravel the mystery.

Line up the genomes of humans and chimps side by side and they differ by little more than 1 per cent. That may not seem like much, but it equates to more than 30 million point mutations. Around 80 per cent of our 30, 000 genes are affected, and although most have just one or two changes (Gene, vol 346, p 215), these can have dramatic effects. The protein made by the human geneFOXP2, which helps us to speak, differs from its chimp counterpart by just two amino acids, for example. And small changes in the microcephalin andASPM genes may underlie big differences in brain size between humans and chimps.

But protein evolution is only part of what makes us human. Also critical are changes in gene regulation - when and where genes are expressed during development - says James Noonan of Yale University. Mutations in key developmental genes are likely to be fatal. But, he says: "Altering the expression of a gene in a single tissue or at a single time can more easily lead to an innovation that is not lethal." Noonan's lab is one of many that are busy comparing gene expression in tissues such as the brain to home in on the key regulatory difference between chimps and humans, most of which have still to be uncovered.

Then there's gene duplication. This can give rise to families of genes that diversify and take on new functions, says Evan Eichler at the University of Washington in Seattle. His lab has identified uniquely human gene families that affect many aspects of our biology, from the immune system to brain development. He suspects that gene duplication has contributed to the evolution of novel cognitive capacities in humans, but at a cost: greater susceptibility to neurological disorders.

Copying errors mean whole chunks of DNA have been accidentally deleted. Other chunks find themselves in new locations when mobile genetic elements jump around the genome or viruses integrate themselves into our DNA. The human genome contains more than 26, 000 of these so-called INDELs, many linked with differences in gene expression between humans and chimps (Mobile DNA, vol 2, p 13).

Even a complete catalogue of genetic differences will not solve the mystery. Much of what makes us human is cultural, passed from generation to generation by learning, says Ajit Varki at the University of California, San Diego. What's more, he says, The co-evolution of genes and culture is a major force in human evolution, famously leaving the descendents of dairy farmers able to digest milk protein, for example. To crack the mystery of human uniqueness we need to know how genomes build bodies and brains, how brains create culture, and how culture eventually feeds back to alter the genome. It remains a distant goal.

人類進(jìn)化十大謎（之一）：我們與黑猩猩：形不似而基因似？

人類和黑猩猩外貌迥異，沒有人會(huì)搞錯(cuò)，但這兩者間的基因相似度卻很高，高過野鼠和家鼠之間的基因相似度。這怎么可能呢？基因組學(xué)研究正在解開這個(gè)謎底。

    把人類和黑猩猩的染色體組并排比較，二者差異略高于百分之一。看似不多，但卻相當(dāng)于三千多萬的點(diǎn)突變。我們30,000個(gè)基因的約百分之八十都會(huì)受影響，盡管多數(shù)僅有一兩處變異（見《基因》第346卷第215頁），但影響可能十分巨大。比如，人類FOXP2基因所制造的蛋白質(zhì)作用于我們的語言能力，只有兩個(gè)氨基酸與黑猩猩的相應(yīng)蛋白質(zhì)不同。此外，微腦磷脂和ASPM基因里的細(xì)微差別可能決定了人類和黑猩猩大腦尺寸的巨大差異。

    但是，蛋白質(zhì)的進(jìn)化只是造就人類的部分原因。耶魯大學(xué)詹姆斯?努南（James Noonan）說，基因規(guī)則的變化同等重要——在生長(zhǎng)過程中基因何時(shí)何地進(jìn)行表達(dá)。關(guān)鍵性發(fā)展基因的突變很可能致命。不過他說：“改變單一組織的基因表達(dá)或僅改變一次某個(gè)基因的表達(dá)更容易帶來安全的創(chuàng)新。”努南的實(shí)驗(yàn)室忙于比較黑猩猩和人類大腦等組織之間的基因表達(dá)，找出關(guān)鍵性的規(guī)則差異；從事這一工作的實(shí)驗(yàn)室還很多，大多尚不為世人所知。

    此外還有基因復(fù)制。西雅圖華盛頓大學(xué)的伊萬?艾克勒（Evan Eichler）說，由此可能產(chǎn)生多樣化和具備新功能的基因族。唯有他的實(shí)驗(yàn)室找出了影響了我們免疫系統(tǒng)到大腦發(fā)展等多個(gè)方面生物性的基因族。他懷疑基因復(fù)制對(duì)人類新認(rèn)知能力的進(jìn)化起著作用，不過是有代價(jià)的：更容易神經(jīng)紊亂。

    復(fù)制錯(cuò)誤就意味著整段的DNA被意外刪除。別的基因段進(jìn)入新的位置，基因組附近出現(xiàn)活動(dòng)的基因成分，或者病毒融入我們的DNA。人類的基因組包含26000多個(gè)這種所謂的基因插入/缺失（INDEL），許多都和人類與黑猩猩之間的基因表達(dá)差異相關(guān)（《可移動(dòng)的DNA》第2卷第13頁）。

    即使取得完整的基因差異圖也無法揭開這個(gè)謎團(tuán)。加州大學(xué)圣地亞哥分校的阿吉特?瓦基（Ajit Varki）說，造就人類的主要是代代傳承的文化。他還說，基因與文化的共同進(jìn)化才是人類進(jìn)化的主要力量，比如這個(gè)眾所周知例子，畜牧業(yè)牧民的后代擅于消化牛奶蛋白。要解開人類特殊性之謎，我們必須了解基因組如何構(gòu)建出身體和大腦，大腦如何創(chuàng)造文化，文化最終又如何反過來改變基因組。這個(gè)目標(biāo)依然遙遠(yuǎn)。