顾秀林：极其精彩的文章，实在来不及翻译。先起一个头。多么需要好的生物学学者参与。为了这篇文章，伪军大队会向我开炮的。有种的去轰炸詹姆斯.夏皮罗。
达尔文的“物竞天择适者生存”假说，早就完成了历史使命，早就该进博物馆；只因有一大帮生物技术专家太爱它，千方百计不让它进博物馆，而把它变成了过时不肯退下的伪科学。于是，真正属于我们时代的、科学的演化论迟迟不能“亮相”，所以才有中国的滚刀肉小方，黄皮白心的老任们（任筑山，2014-6-1）死心塌地的维护行动和拙劣表演，为死去很久的转基因金科玉律“中心法则”招魂。不就是因为基因专项工程的钱太多吗？不就是因为转基因的“钱途”耀瞎了他们的双眼吗？不就是因为找到了得心应手、向公众投毒又难以被抓住血手的“高招”了吗？生物科学走到这境界，已是十足的邪恶！伪军衮衮，政客孜孜，末世死光，笼罩华夏。
真正的科学不在自称主流的大小科霸的嘴里。我们时代的新遗传学早已脱颖而出，陈旧的、决定论的分子生物学该进博物馆了，根据那个错误的理论制造出来的转基因“不可阻挡的趋势”，日暮途穷，垂死挣扎，看看借央视舞台裸演的老任那副嘴脸即可知。愿意为它殉葬的人还有很多，不要紧——真的假不了，愿意殉葬的，排好队，别掉队，都过去，一刀切才能切彻底。下面是摘译。
演化是天然的基因工程 来ISIShttp://www.i-sis.org.uk/Evolution_by_Natural_Genetic_Engineering.php
1. 切割加混合 vs 随机事件
美国芝加哥大学詹姆斯.夏皮罗，早在1980年代就以新遗传学的“流动基因组“学说”动摇了基因学说的根基。(2，4，5：与流动的基因组一起生存， ISIS刊发)。 半个世纪以来，老式基因学说的原理一个又一个成了“例外”，终于有一天，例外的数量超过了还能成立的规则。在发表于1997年的论文中[1], 夏皮罗雄辩地挑战了新达尔文主义的“法则”：即演化出自于随机突变基础上的自然选择...(Shapiro made a powerful case against the neo-Darwinian dogma that evolution occurs by the natural selection of random mutations.)......
2. 适应性突变中有精确的天然基因工程特征
‘Adaptive’ mutations involve features of precise natural genetic engineering
3. 在一篇新论文中，夏皮罗把基因组和计算机并列，清晰地演示了二者的异同，纠正了对基因组的很多误解——“人们一直把基因组当作ROM--只读存储，出现改变是因为转录错误和事故(注7 第258页)， 我改变视角，把基因组理解为计算机的读写数据(RW)，它常规性地被细胞的操作进行修饰修饰并命名。”
部分原文：
ISIS Report 02/06/14
New Genetics and Evolution
Evolution by Natural Genetic Engineering
########################################
New findings in genetics show that evolution happens by precisely targeted
natural genetic engineering and not by the natural selection of random
mutations, says leading molecular biologist James Shapiro, but what are the
implications for the safety of GMOs and social policies? Dr Mae Wan Ho
Cut and splice vs random accidents
I have been awaiting his latest papers for years ever since he first introduced
the concept of ‘natural genetic engineering’ in 1997 [1], referring to organisms
themselves using ‘cut and splice’ techniques to meet environmental challenges,
same as those used by human genetic engineers in the lab. It was a major
inspiration for my book [2] Genetic Engineering: Dream or Nightmare? (ISIS
publication) warning of dangers from genetically modified organisms (GMOs)
released into the environment.
James Shapiro at University of Chicago Illinois in the United States is among
the pioneers who discovered the new genetics of the ‘fluid genome’ that, by the
early 1980s, had already shaken the scientific establishment to its roots [3]
(see also [2, 4], [5] Living with the Fluid Genome, ISIS publication). All the
basic tenets of conventional genetics that had dominated science and society for
at least half a century were being eroded by exceptions upon exceptions, until
the exceptions outnumbered and overwhelmed the rules.
In his 1997 paper [1], Shapiro made a powerful case against the neo-Darwinian
dogma that evolution occurs by the natural selection of random mutations.
Bacterial genomes typically have a modular structure consisting of sets of genes
(operons) expressed together. Operons have a characteristic internal structure,
with coding regions for regulator protein(s), structural/enzyme proteins and
several control elements. Every protein coding sequence in turn contains several
domains each with a defined function. Many operons are dispersed throughout the
genome, equipped with different combinations of similar regulatory/control
genetic elements and forming overlapping, often extensive ‘regulons’ (gene
expression networks) finely tuned to different stages of cell growth and
development and changing environmental conditions. Staggering multitudes of
protein-effector, protein-protein, protein-nucleic acid, and nucleic acid-
nucleic acid interactions are involved, all highly specific for every occasion.
Not surprisingly, genomes have special mechanisms for correcting base sequence
errors during DNA replication.
It is extremely hard to imagine how such a genome could have been assembled or
changed piece-meal by the natural selection of independently occurring random
mutations in different genetic elements. On the other hand, a simple copying
(amplification) process followed by cut and splice different sequence elements
together would be easily accomplished. Cells have all the enzymes and cofactors
required for such feats of natural genetic engineering. In fact, artificial
genetic engineering is possible only by using the enzymes isolated from the
bacteria themselves, albeit without the precision and finesse of natural genetic
engineering.
‘Adaptive’ mutations involve features of precise natural genetic engineering
Shapiro discovered ‘adaptive’ mutations in bacteria (recently confirmed, see [6]
Non-Random Directed Mutations Confirmed, SiS 60). He investigated an E. coli
system that depends on generating a fusion lacZ protein, the b-galactosidase
that breaks down lactose to galactose and glucose. The bacterial virus (phage)
Mu was used to construct a strain in which a defective lacZ coding sequence
without its promoter - a control element required for transcription - and
carrying an ochre triplet (a stop codon) at codon 17 - so the transcript cannot
be translated fully - was aligned in tandem with another coding sequence araB
(from the arabinose operon) that has an intact promoter [1]. In that way, a
precise deletion of intervening sequence is needed to form the fusion b-
galactosidase protein capable of functioning to break down lactose and enable
the cell to growth on a selective medium with lactose as the sole carbon source.
Shapiro originally thought that the Mu prophage (phage integrated into the
bacterial genome) would be the passive source of homology (sequence similarity)
to enable the fusion to take place by homologous recombination to loop out the
intervening sequence, and such ‘spontaneous’ break-rejoin events would generate
the actual fusions by removing all blocks to transcription and translation
between araB and a site in lacZ downstream of the ochre triplet codon. But
detailed studies showed that the Mu prophage played an active role in the araB-
LacZ fusions using its transposase enzyme, and the process was precisely
regulated by the cell. Many different proteins and DNA sequences have to come
together in choreographed succession to form and rearrange the nucleoprotein
complexes necessary for directing the precise cut and splice operations. A large
number of the molecular players have been identified since. In other words, the
fusion events happen as the result of accurate natural genetic engineering
carried out by the E. coli cell.
As mobile genetic elements like Mu are found in all organisms, Shapiro thought
it reasonable to hypothesize that the regulatory aspects of the mutational
process exemplified by the araB-LacZ system might apply generally to other
examples of adaptive mutations (see [6]) and described the numerous cellular
functions involved in different cases. He wrote [1, p.103]: “The depth of
regulatory interactions between cellular signal transduction networks and
natural genetic engineering systems is likely to prove typical rather than
exception.”
Natural genetic engineering has large implications for evolution, Shapiro
pointed out. First, large scale coordinated changes within the genomes of single
cells are possible because a particular natural genetic engineering system can
be activated to operate at multiple sites in the genome. Second, there is
opportunity for adaptive feedback to make genetic changes, thereby greatly
accelerating evolutionary change during episodes of crisis.
From ROM to RW genome
In his new papers, Shapiro draws an illuminating parallel between the genome and
the computer [7, 8]; at the same time correcting some widely held misconceptions
about the genome.
“The genome has traditionally been treated as a Read-Only Memory (ROM) subject
to change by copying errors and accidents.” Shapiro writes [7, p. 268]: “I
propose that we need to change that perspective and understand the genome as an
intricately formatted Read-Write (RW) data storage system constantly subject to
cellular modifications and inscriptions.”
The ROM view of the genome is encapsulated by Sydney Brenner in his 2012 Alan
Turing Centennial tribute [9]: “Turing’s ideas were carried further in the 1940s
by mathematician and engineer John von Neumann, who conceived of a ‘constructor’
machine capable of assembling another according to a description. A universal
constructor with its own description would build a machine like itself. To
complete the task, the universal constructor needs to copy its description and
insert the copy into the offspring machine. Von Neumann noted that if the
copying machine made errors, these ‘mutations’ would provide inheritable changes
to the progeny.”
This static mechanical view of the genome is a far cry from reality. Even to
reproduce a single protein – originally conceptualised as a single message –
requires elaborate cut and splice operations. The international research
consortium project ENCODE (Encyclopedia of DNA Elements) data have revealed that
the vast majority of genomic DNA include many ‘non-coding’ segments [10, 11].
The term ‘gene’, a theoretical construct that has never been possible to define
rigorously, is now known to be scattered in bits across the genome, overlapping
with bits of multiple genes that have to be spliced together to make a messenger
(m)RNA for translation into protein. The term now used for the bits is ‘coding
sequences’ or exons.
The Turing tape analogy does not take into account the actual physical
participation of the genome in productive and regulatory interactions. The
concept of a Read-Only Turing genome also fails to recognize the essential
‘Write’ capability of a universal Turing machine, which fits remarkably well
with the ability of cells to make temporary or permanent inscriptions in DNA.
(Of course, it is by no means all down to the genome. A genome outside a cell
can do nothing. The numerous claims that synthetic biologists have created life
in the laboratory are spurious, as they all depend on putting a synthetic genome
into a pre-existing cell [12] (Synthetic Life? Not By a Long Shot, SiS 47).
Moreover, it is not so much the cell, but rather the nature of living protoplasm
that keeps eluding our grasp [13, 14] The Rainbow and the Worm, The Physics of
Organisms, and Living Rainbow H2O, ISIS publications.)
Shapiro [1, 7, 8] distinguishes modifications of DNA (rearrangements, deletions,
insertions, mutations) - which he regards as natural genetic engineering proper
- from epigenetic changes involving DNA/histone marks, or via non-coding RNA
species that occur constantly in real time within the life cycle of the cell or
organism. In my view, this distinction is artificial. There is no real
separation between epigenetic and genetic; they form one seamless continuum in
molecular mechanisms that interact with one another directly. In a further paper
[15], Shapiro himself proposes that during ‘life history events’ such as
hybridization and chromosome doubling, viral or bacterial infections, exposure
to environmental toxins, etc., epigenetic changes are often accompanied by
mobilization of transposable elements that change the genome. And non-coding
RNAs (ncRNAs) are involved in mobilizing transposons and in targeting specific
changes in chromatin, the DNA histone protein complex that forms a chromosome.
Another common connection between epigenetic and genome change is that
processed, alternatively spliced RNA can be reversed transcribed and inserted
into the genome. On the other hand, certain altered (reformatted) states of
/chromatin can be passed on to subsequent generations; i.e., they are inherited
like a mutation. And various species of interference RNA can also act
independently as genetic material to perpetrate epigenetic changes across many
generations, as part and parcel of the hereditary legacy of the organism (see
[16] RNA Inheritance of Acquired Characters, SiS 63). In the new genetics of the
‘fluid genome’, the genome is no longer the constant and unchanging entity
previously assumed. Hence I use the term “natural genetic modification” for the
totality of changes in the genetic information of cells and organisms as they
experience their environments that are all necessary for survival, and some of
which are passed on to the next generation(s) [17].
We shall follow Shapiro’s story [7, 8] on actual modifications of DNA base
sequence and the genome structure before dealing with implications on artificial
genetic modification and for society in general. The rest of this series of
articles will elaborate on the epigenetic aspects of natural genetic
modification.
Read the rest of this report here
http://www.i-sis.org.uk/Evolution_by_Natural_Genetic_Engineering.php
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