拉马克真是一无是处？


              [原作者]：Michael Balter   [译者]：宋非


　　今天，人们通常只记得拉马克提出了一种现在认为错误不堪的进化理论。按
照这种进化理论，父母把自己在生活中获得的特性传递给下一代，因此就发生了
进化。人们不太知道的是,拉马克(1744-1829)这位法国的自然学家是他所处时代
里最伟大的科学家之一。他是第一个系统研究无脊椎动物的科学家，是最早提出
动植物随时间的变化是由于进化，而不是神干预造成的科学家之一。不过，在20
世纪初，他的进化理论被达尔文的自然选择理论和孟德尔的遗传定理所取代。更
为吊诡的是，他的名字从此被人们紧紧地同前苏联斯大林时代的农学家李森科连
在一起。李森科当时逼迫前苏联的遗传学家要么接受拉马克的理论，要么停止遗
传学研究。

　　不过，拉马克的名字近来又开始出现在科学文献中。其中的根本原因是“特
异遗传(epigenetics)”研究的爆炸性进展。“特异遗传”研究不改变DNA序列，
但出现的遗传表达变化。某些“特异遗传”变化能传递给下一代，从而产生似乎
有违孟德尔遗传学的现象。虽然这些新发现并不支持拉马克的整个理论，但它们
引出了“特异遗传”可能在进化中起作用的可能性。哦力冈大学的分子遗传学家
Selker评论到：我现在不知道有证据表明拉马克理论有对的成分，但这种可能是
存在的。现在越来越清楚的是：特异遗传机制确实在生物中扮演重要，有时甚至
是关键性的作用“。

　　特异遗传变化，包括通过DNA片断甲基化后,此基因不再被细胞中蛋白质组成
的装置阅读,从而造成的基因的“沉默(silencing)”。特异遗传变化与许多过程
有关，包括基因调控，发育甚至癌症。虽然这些基因表达的变化可以在细胞分裂
时由母代传递给子代细胞，比如肌肉细胞分裂，或者癌细胞增生形成肿瘤，但这
些变化在生殖细胞形成时通常会被抹去。

　　不过越来越多的证据表明：在一些情形下，特异突变并不会被抹去。这种现
象曾经在植物，果蝇和酵母中观察到过。第一例哺乳动物中令人信服的观察发表
在1999年十一月号的《自然：遗传学》杂志上。这一工作是由澳大利亚悉尼大学
的生物化学家Whitelaw和其他苏格兰，美国的合作者共同完成。Whitelaw的小组
所用的材料是一个遗传背景完全相同的自交小鼠系，按理它们应该完全相同。但
是这些小鼠的皮毛颜色差异很大，从黄色到各种颜色的杂合。而且更有趣的是：
新生小鼠的皮毛颜色很大程度受母鼠的影响，但不受父鼠的影响。黄皮毛的母鼠
所生的黄色小鼠比杂色小鼠多。同理，杂色母鼠所生的杂色小鼠比黄色小鼠多。
这一现象就违背了孟德尔原则，即性状随机分布于子代。

　　该小组发现：皮毛的颜色明显依赖于在控制皮毛颜色基因agouti上游的调节
DNA片断的甲基化程度。也就是说,这依赖于这一甲基化状态在多大程度上通过生
殖细胞从母鼠传递给后代。英国剑桥大学的发育遗传学家Surani对此评论到：“
通常，生殖细胞是非常有效抹去特遗传修饰的机制。但Whitelaw的文章表明，这
一原则也有例外。”至于是否特异突变也象 DNA序列改变一样在进化中扮演重要
的作用，如有利于达尔文的自然选择发生作用。Surani认为这部分取决于这种特
异遗传现象同经典的遗传突变相比，比例有多大。

　　Surani和其它研究者认为，成体动物获得的特异突变传给下一代的可能性大
大地为生殖细胞在生命的早期就被隔离开来的事实所限制。在哺乳动物中，生殖
细胞在胎儿出生前就已经形成并迁移到胚胎的卵巢和精囊中，这样就使得它们不
受成体中特异遗传修饰的影响。但在植物中，情形可能完全不同，因为它们在生
命过程的较晚时期才产生生殖细胞。在1999年9月9日的《自然》杂志上，英国
Norwich，John Innes中心的分子遗传学家Coen和同事报道了云兰属植物Linaria 
vulgaris的一个突变体特征。这一特异突变导致它的花从双面对称变为辐射状。
在突变体植物中，一个叫Lcyc基因广泛甲基化，因此不能表达。这一甲基化状态
在云兰属植物中是能遗传的。Coen和同事认为这种特异突变可能在植物进化中同
时具有的短期和长期的效应，因为甲基化的基因更容易转化为经典的突变,即DNA
序列改变。

　　Coen指出，同拉马克一样，达尔文也认为“获得性遗传”在进化中起作用。
两者之间的分歧在于拉马克认为进化是由生物内部需要驱动，从而适应环境的，
最著名的例子是说长颈鹿因为想吃到较高树枝上的树叶，不断拉长脖子，并把这
种长脖的表型性状传给子孙后代。而达尔文则认为是对遗传改变的自然选择，而
不是内部需要，驱动适应性变化。Coen认为，虽然现在特异突变研究的结果挑战
经典的教条：“只有DNA序列的改变才是唯一的可遗传突变”,但这些结果并不支
持成体生物在生命过程中获得的形态变化能以拉马克的方式遗传下去。

　　但是，也有研究者认为，新的研究确实提供了一种潜在的机制，这种机制使
得特异遗传变化能具有适应性作用。Selker评论道：虽然把特异遗传性状的适应
性特征同拉马克关于长颈鹿脖子如何变长相比确有牵强附会之嫌。但我们确实知
道环境因子，比如温度，就能影响特异遗传标志，如甲基化”。现在看来有一点
已经是明确的：特异遗传研究的爆炸已经帮助恢复了拉马克在科学史上的地位，
虽然他在主要的方面错了。Coen说道：“拉马克是进化论的真正先驱”。

　　原载于2000年，四月7号的权威科学杂志：《科学》 (38页)


　　[译者按]：进化论，进化论中的各种学派存在者各种不同的看法，这在科学
中是极端正常的。由于进化论的假说性质，各种看法的证明或证伪需要大量，艰
苦的研究工作。

　　凭著一些过时的教科书，就随意把某种学说打成伪科学，然后开展网上大批
判运动，这本身就是极端不严肃，甚至反科学的。

　　由于种种原因，“获得性遗传”被人们同政治运动紧紧联在一起。造成某些
人不必要的误会，认为只要是关于“获得性遗传”，就先天是错误的。实际上，
科学应该同政治分开，科学研究有自己的规律。现在，由于“特异遗传”研究的
爆炸性结果，“获得性遗传”在某些情况下可能已经不是什么特别新鲜的东西。
这里翻译了权威科学杂志《科学》上关于这方面研究进展的报道，希望能表明真
正的科学研究没有禁区，而教科书上的知识通常落后于科学的前沿研究，所以不
能用来指导科学研究。难道因为特异遗传现象与教科书上的介绍不同，我们就不
要去研究它。要知道，特异遗传现在发现与癌症密切相关。


~~~~~~~~~~~~~

原文附后：

GENETICS:
Was Lamarck Just a Little Bit Right?

Michael Balter

Pity poor Jean-Baptiste Lamarck. Today, he is remembered mostly for
the discredited theory that evolution occurs when parent organisms
pass on to their offspring characteristics they have acquired during
their lifetimes. But this French naturalist, who lived from 1744 to
1829, was one of the great scientists of his age. He was the first to
study invertebrate animals systematically, and he was an early champion of 
the idea that evolution rather than divine intervention was responsible 
for changes in plants and animals over time. But by the early 20th century, 
Lamarck's concept of evolution had been superceded by Darwin's theory of 
natural selection and the genetic laws of Gregor Mendel. And since then 
his name has become inextricably linked to that of his most notorious 
disciple--the Stalin-era agronomist Trofim Lysenko--who forced Soviet 
geneticists to accept Lamarckian ideas or be banned from doing research 
(see main text).

Recently, however, Lamarck's name has been creeping back into the
scientific literature. The reason: an explosion in the field of
epigenetics, the study of changes in genetic expression that are not linked
to alterations in DNA sequences. Some of these epigenetic changes can be
passed on to offspring in ways that appear to violate Mendelian genetics.
And although these new findings do not support Lamarck's overall concept,
they do raise the possibility that "epimutations," as they are called,
could play a role in evolution. "I don't know of any evidence that Lamarck
was even a little bit right, but this is possible," says molecular
geneticist Eric Selker of the University of Oregon, Eugene. "It is
increasingly clear that epigenetic mechanisms play important, sometimes
critical, roles in biology."

Epigenetic changes, which include the "silencing" of genes by such
biochemical tricks as attaching methyl groups to segments of DNA so they
will not be read by the cell's protein-making machinery, are involved in a
host of processes, including gene regulation, development, and even cancer
(Science, 15 October 1999, p. 481). Although these alterations in gene
expression can clearly be passed from mother to daughter cells--for
example, when a muscle cell divides into two or cancerous cells proliferate
to form a tumor--they are normally "erased" when the germ cells, which give
rise to the next generation, are formed.

Yet evidence is accumulating that sometimes the epimutations are not
erased. This phenomenon has been spotted in plants, fruit flies, and yeast.
And the first convincing case in mammals was reported in the November 1999
issue of Nature Genetics by biochemist Emma Whitelaw at the University of
Sydney in Australia and co-workers in Scotland and the United States.
Whitelaw's team worked with an inbred strain of mice in which all are
genetically identical and so should look exactly the same. But the coat
colors of these mice varied wildly, ranging from yellow to mottled with
every combination in between. Moreover, the coat color of newborn mice was
highly influenced by the color of the mother, but not of the father: A
yellow mother had more yellow pups than mottled, and a mottled mother had
more mottled pups than yellow, violating Mendelian principles that traits
are randomly distributed during reproduction.

The team found that coat color apparently depends on the degree to which a
stretch of regulatory DNA just upstream from a gene controlling coat color,
called agouti, is methylated. This in turn depends on how much of this
methylation state, if any, has been transferred from the mother through the
germ line to its offspring. Azim Surani, a developmental geneticist at the
University of Cambridge in the United Kingdom, comments that the germ cells
are normally "a very efficient cleaning machine, which wipes out many of
these epigenetic modifications. ... The [Whitelaw] paper shows there are
exceptions to this rule." As for whether epimutations could play an
important role in evolution--that is, whether they, like alterations in DNA
sequence, could be favored by Darwinian natural selection--Surani says this
partly depends on whether they are fairly common, compared to classic
genetic mutations, or rare.

Moreover, Surani and other researchers say, the likelihood that
epimutations acquired by adult organisms will be passed on to their
offspring is limited by the fact that in most animals the germ cells are
segregated very early in life. In mammals, the germ cells are formed and
migrate to the embryonic ovaries and testes long before the fetus is born,
presumably shielding them from epigenetic modifications in the adult. But
the situation might be different in plants, which produce their germ cells
much later in their life cycle. In the 9 September 1999 issue of Nature,
molecular geneticist Enrico Coen and colleagues at the John Innes Centre in
Norwich, U.K., reported that a mutant version of the toadflax plant
(Linaria vulgaris)--which results in flowers with radial rather than
bilateral symmetry--is due to an epimutation. In the mutant plant, a gene
called Lcyc is extensively methylated and thus not expressed--and this
methylated state is heritable by subsequent generations of toadflax plants.
Coen and his colleagues conclude that such epimutations might have both
short- and long-term effects on plant evolution, both in their own right
and because methylated genes are more susceptible to classic mutations that
alter DNA sequences.

Coen points out that Darwin, like Lamarck, believed that the inheritance of
acquired characteristics played a role in evolution. The main difference
between them was that Lamarck thought evolution was driven by an organism's
inner need to adapt to its environment, such as in the famous example of
the giraffes who stretched to reach the upper branches of trees and then
passed on the phenotypic trait for longer necks to their progeny. Darwin,
on the other hand, posited that natural selection of genetic alterations,
rather than some "inner striving," drives adaptive changes. Coen cautions
that although the new studies of epimutations challenge the dogma "that the
only heritable mutations of significance are caused by DNA sequence
changes," they offer no support at all for the idea that morphological
changes acquired during the lifetime of an adult organism can be inherited
in the Lamarckian sense.

But some researchers say that the new research does suggest a potential
mechanism for how epigenetic changes could play an adaptive role. "Although
it would be stretching it to regard epigenetic traits as adaptations
comparable to Lamarck's view of how the giraffe acquired its long neck,"
comments Selker, "we do know that environmental factors, such as
temperature, can influence epigenetic marks such as methylation." And one
thing seems sure: The explosion in epigenetic research has helped restore
Lamarck to his rightful place in scientific history, even if he did get the
big picture wrong. Says Coen: "Lamarck was a true pioneer of evolutionary
theory."