1959年,一系列的文章报道了大肠杆菌(Escherichia coli)的高频转导(Hfr)菌株可以将遗传信息传递给特定的 鼠伤寒沙门氏菌(Salmonella typhimurium)突变菌株。同年,Tomochiro Akiba和Kunitaro Ochiai发现病原菌中的抗性质粒,而这一发现直接导致了携带抗性的质粒可以在不同菌种间转移现象的发现,这实际上就宣告了 野生型菌株间存在着 水平基因转移。
然而,水平基因转移作为一种概念,并不是一开始就伴随着其现象的发现而出现的。直到20世纪90年代,由于下列原因,人们才逐步使用水平基因转移的概念来解释所遇到的水平基因转移现象,并形成研究热点。基因工程生物,特别是基因工程微生物(gene engineered organisms, GEOs, or gene engineered microorganisms, GEMs)的应用,及被释放到环境中后的安全性问题。 抗药性病原菌的大量出现,许多药物,特别是抗生素已经不能抑制或杀死原来敏感的病原菌,这已不仅仅是 基因突变可解释的,可能与抗药性基因的水平转移有关。已发现基因的转移不仅仅是发生在细菌之间,而且也发生在细菌与高等生物之间,甚至是高等生物之间。
细菌中以F质粒为媒介的 接合作用和以病毒( 噬菌体)为媒介的 转导作用是最普通的水平基因转移,而且这种转移还不只是发生在细菌之间,还发生在细菌与高等生物之间,例如在 土壤微生物中,存在于根癌 土壤杆菌(Agrobacterium tumefaciens)中的200kb Ti质粒上的 T-DNA基因片段可整合进 植物细胞的 基因组中。即: 根癌土壤杆菌中的T-DNA可转移到植物细胞核内。T-DNA还可以携带一定的外源基因,在植物基因工程中被广泛地用做 基因转移载体[8]。此外, Ri质粒也可以协助遗传物质在细菌与植物间进行 水平基因转移。有关细菌与 动物细胞间的水平基因转移,在1991年,Falkow综合论述了有些特定的细菌属可以入侵 哺乳动物细胞的详细情况。Patrice Courvalin研究表明,弗氏 志贺菌(Shigella flexneri)及E. coli的入侵型菌株以携带质粒进入哺乳动物细胞,质粒并可以整合进 基因组中稳定地在 子代细胞中表达。
1996年,Baur发现在从自然环境中采集的含一定离子的天然水样中,大肠杆菌可通过其内在调节机制建立自然 感受态[12]。能够在自然环境中“直接”摄取 外源DNA,这对原本认为大肠杆菌是不能建立自然感受态的传统概念是一种挑战。此外, 枯草芽孢杆菌建立自然感受态的能力也早已得到人们的肯定,其基因组上有10多个基因与感受态的建立有关。随着环境中具有转化活性的 DNA分子及 感受态细胞的发现,自然转化在 水平基因转移中的作用成为人们关注的焦点。所谓自然遗传转化是不需要任何媒介的“裸露”DNA分子与自然感受态细胞间相互作用的一种 基因转移方式,可以发生在细菌之间,也可以发生在细菌与其它真核生物之间。因为自然遗传转化不需要致育质粒和 噬菌体作为媒介,甚至不受时空的限制,可以发生在不同的生物之间,所以被认为很可能是水平基因转移的重要途径。在这一途径中,一种新的现象已引起人们的极大兴趣,即细菌细胞能主动分泌DNA到环境中,并具有转化活性,这不仅对传统的不涉及供体的自然转化概念提出了新的挑战,而且也为水平基因转移的深入研究提供了新的内容。特别近来有报道表明,细菌在逆境条件下形成生物膜(biofilm)的机制与细菌分泌到胞外的DNA密切相关,更引起人们广泛的关注。由前可知,无论是在正常条件下,还是在逆境条件下,尤其是后者,细菌主动分泌DNA到环境中和从环境中摄取DNA都得到了有力的证明。如果能够在逆境条件下,找到细菌主动分泌及摄取DNA的结合点,有利于进一步揭示 水平基因转移的机理。
3 基因组序列分析和水平基因转移随着基因工程的深入开展,人类及其它生物基因组测序工作相继完成,人们发现不同物种之间,甚至亲缘关系很远的生物之间 基因组上有大量 同源基因存在。
在 三域系统的基因组相互比对中,发现大量存在水平基因转移现象。海栖热袍菌MSB8(Thermotoga maritima MSB8)是一种属于 细菌域的 嗜热细菌,在其基因组中含有1872个预测的 编码区,其中有1014个(54%)功能已知。在与 古生菌的比对中,发现有24%的基因与古生菌基因相近,即有近1/4的基因来源于古生菌,成为 古菌与细菌之间进行侧向 基因转移的有力证据。细菌基因组上含有来自高等生物的基因也有不少报道。如耐放射异常球菌(Deinococcus radiodurans)含有几个只有在植物中才有的基因; 结核分枝杆菌(Mycobacterium tuberculosis)的 基因组上至少含有8个来自人类的基因,而且这些基因编码的蛋白质能帮助细菌逃避 宿主的防御系统,显然这是结核分枝杆菌通过某种方式从宿主那儿获得了这些基因为自己的生存服务。 人类基因组测序工作的完成也进一步证实了 水平基因转移的普遍性和远缘性。在人类基因组上已发现了223个来源于细菌的基因,这些基因无疑是通过水平基因转移机制获得的[21]。但在 基因转移的时间上,目前还存在争议。除了基因组比对外,人们还对部分蛋白质序列做了比对分析,发现有许多水平基因转移存在的证据。在 细胞色素c的 序列比对中认为长须银柴胡(Stellaria longipes)和 鼠耳芥(Arabidopsis thaliana)很有可能与 噬菌体之间发生过水平基因转移[23]。 铜绿假单胞菌(Pseudomonas aeruginosa)中类似真核的磷酸脂酶D(PLDS)的遗传学和生化分析指出,编码该酶的基因pldA是通过来自真核的 水平基因转移获得的。
在这个意义上,水平基因转移不仅仅是一个 基因转移的过程,实际上它是一个复杂的多步骤过程。Jonathan将此大致分为6个步骤。首先要被转移的遗传物质在供体中进化。当达到某一点时,遗传物质通过载体(如病毒)或者直接(如 接合)或者间接(如转化)地进行转移。这些遗传物质必须获取能够在受体中长期存在的形式。不同的转移和存留方式决定了不同的水平基因转移类型。被受体接受的遗传物质在受体群落中广泛传播,即使这些遗传物质的传播是符合中性法则的,但是自然选择的压力会有可能促进这一传播过程(如抗生素抗性的选择)。而这一过程对供体和受体的进化都具有影响,最终有可能会产生一个新的品系,这被称之为“改良(amelioration)”过程。这一过程实际上是漫长而复杂的。
这种 基因转移到底发生在什么时候,目前有两种观点。一种认为 水平基因转移发生在远古时候的早期生命,即单一的共同细胞祖先产生了所有的现代生物;另一种观点则认为,除了早期生命在进化过程中进行了大量水平基因转移外,现在的生命,即在 物种形成清晰的谱系之后仍能毫无困难地交换基因。水平基因转移在历史上的大量证据,使人们有必要对 生物进化理论进行重新审视。Doolittle认为许多原本在生物进化理论中基础的概念都需要经过重新审视。传统的简单分支的 系统发育树不能成为表现众多生物亲缘关系的最佳方式,而网络性的或类网状的 系统发育模式才能给予它们恰当的描述。同时,水平基因转移在微生物进化中还是被认为是一种重要的推动力量。随着 转基因生物的商业化过程,转基因工程的 生物安全性逐步受到人们的重视。有研究认为距今20亿年至10亿年之间,发生了大量 水平基因转移的事实。假设这是正确的话,在人为介入水平基因转移之后,大量 穿梭载体及特异人工遗传物质的出现并释放到实验室之外后,是否会出现水平基因转移的第二次大爆发呢?在距今20亿年至10亿年之间,三域生物之间发生了大量的水平基因转移事件。认为现代真核生物的核(nu)来自于 古细菌, 线粒体(mi)和 叶绿体(ch)来自 真细菌。同时还发生了许多其它对现代生物影响深远的水平基因转移事件(源自Michael Syvanen, 2002)。
近年来,发现自然环境中存在大量具有转化活性的 DNA分子以及能主动摄取 外源DNA的 感受态细胞,使得人们对环境中发生的 水平基因转移有了新的认识,也必然引起人们对GEMs使用安全性的更深层次的思考。如果说自然环境微生物之间遗传物质的交流是一种正常的生态平衡系统,或者说是一种极其缓慢的优胜劣汰的进化过程,那么为了提高农业生产,甚至革新整个农业生产面貌,或治理环境污染,或其它方面的应用,人为地向环境中加入大量的人工构建的GEMs或其它的GEOs,也许是一种加速进化的“ 人工进化”过程,这个过程的结果是喜是忧?还是二者兼有?目前仍是未解决的问题,也是颇具争议的问题。水平基因转移及其产生的 生态效应的深入研究,将有助于对GEOs做出新的评价,使得基因工程技术及 转基因生物的应用发挥更辉煌的作用。
Horizontal gene transfer (HGT) refers to the transfer of genes between organisms in a manner other than traditional reproduction. Also termed lateral gene transfer (LGT), it contrasts with vertical transfer, the transmission of genes from the parental generation to offspring via sexual or asexual reproduction. HGT has been shown to be an important factor in the evolution of many organisms.[1]
Horizontal gene transfer is the primary reason for bacterial antibiotic resistance,[1][2][3][4][5] and plays an important role in the evolution of bacteria that can degrade novel compounds such as human-created pesticides[6]and in the evolution, maintenance, and transmission of virulence.[7] This horizontal gene transfer often involves temperate bacteriophages and plasmids.[8][9] Genes that are responsible for antibiotic resistance in one species of bacteria can be transferred to another species of bacteria through various mechanisms (e.g., via F-pilus), subsequently arming the antibiotic resistant genes' recipient against antibiotics, which is becoming a medical challenge to deal with.
Most thinking in genetics has focused upon vertical transfer, but there is a growing awareness that horizontal gene transfer is a highly significant phenomenon and among single-celled organisms perhaps the dominant form of genetic transfer.[10][11]
Artificial horizontal gene transfer is a form of genetic engineering.
Contents
[hide]
- 1History
- 2Mechanism
- 3Inference
- 4Viruses
- 5Prokaryotes
- 6Eukaryotes
- 7Artificial horizontal gene transfer
- 8Importance in evolution
- 8.1Scientific American article (2000)
- 8.2Genes
- 9See also
- 10Sources and notes
- 11Further reading
History[edit]
Horizontal genetic transfer was first described in Seattle in 1951 in a publication which demonstrated that the transfer of a viral gene intoCorynebacterium diphtheriae created a virulent from a non-virulent strain,[12] also simultaneously solving the riddle of diphtheria (that patients could be infected with the bacteria but not have any symptoms, and then suddenly convert later or never),[13] and giving the first example for the relevance of the lysogenic cycle.[14] Inter-bacterial gene transfer was first described in Japan in a 1959 publication that demonstrated the transfer of antibiotic resistance between different species of bacteria.[15][16] In the mid-1980s, Syvanen[17] predicted that lateral gene transfer existed, had biological significance, and was involved in shaping evolutionary history from the beginning of life on Earth.
As Jain, Rivera and Lake (1999) put it: "Increasingly, studies of genes and genomes are indicating that considerable horizontal transfer has occurred between prokaryotes"[18] (see also Lake and Rivera, 2007).[19] The phenomenon appears to have had some significance for unicellulareukaryotes as well. As Bapteste et al. (2005) observe, "additional evidence suggests that gene transfer might also be an important evolutionary mechanism in protist evolution."[20]
There is some evidence that even higher plants and animals have been affected and this has raised concerns for safety.[21] It has been suggested that lateral gene transfer to humans from bacteria may play a role in cancer.[22]
Richardson and Palmer (2007) state: "Horizontal gene transfer (HGT) has played a major role in bacterial evolution and is fairly common in certain unicellular eukaryotes. However, the prevalence and importance of HGT in the evolution of multicellular eukaryotes remain unclear."[23]
Due to the increasing amount of evidence suggesting the importance of these phenomena for evolution (see below) molecular biologists such as Peter Gogarten have described horizontal gene transfer as "A New Paradigm for Biology".[24]
Some have argued that the process may be a hidden hazard of genetic engineering as it could allow transgenic DNA to spread from species to species.[21]
Mechanism[edit]
There are several mechanisms for horizontal gene transfer:[1][25][26]
- Transformation, the genetic alteration of a cell resulting from the introduction, uptake and expression of foreign genetic material (DNA orRNA).[27] This process is relatively common in bacteria, but less so in eukaryotes.[28] Transformation is often used in laboratories to insert novel genes into bacteria for experiments or for industrial or medical applications. See also molecular biology and biotechnology.
- Transduction, the process in which bacterial DNA is moved from one bacterium to another by a virus (a bacteriophage, or phage).[27]
- Bacterial conjugation, a process that involves the transfer of DNA via a plasmid from a donor cell to a recombinant recipient cell during cell-to-cell contact.[27]
- Gene transfer agents, virus-like elements encoded by the host that are found in the alphaproteobacteria order Rhodobacterales.[29]
A transposon (jumping gene) is a mobile segment of DNA that can sometimes pick up a resistance gene and insert it into a plasmid or chromosome, thereby inducing horizontal gene transfer of antibiotic resistance.[27]
Inference[edit]
Main article: Inferring horizontal gene transfer
Horizontal gene transfer is typically inferred using bioinformatic methods, either by identifying atypical sequence signatures ("parametric" methods) or by identifying strong discrepancies between the evolutionary history of particular sequences compared to that of their hosts.
Viruses[edit]
The virus called Mimivirus infects amoebae. Another virus, called Sputnik, also infects amoebae, but it cannot reproduce unless mimivirus has already infected the same cell.[30] "Sputnik’s genome reveals further insight into its biology. Although 13 of its genes show little similarity to any other known genes, three are closely related to mimivirus and mamavirus genes, perhaps cannibalized by the tiny virus as it packaged up particles sometime in its history. This suggests that the satellite virus could perform horizontal gene transfer between viruses, paralleling the way that bacteriophages ferry genes between bacteria.".[31] Horizontal transfer is also seen between geminiviruses and tobacco plants.[32]
Prokaryotes[edit]
Horizontal gene transfer is common among bacteria, even among very distantly related ones. This process is thought to be a significant cause of increased drug resistance[1][33] when one bacterial cell acquires resistance, and the resistance genes are transferred to other species.[34][35]Transposition and horizontal gene transfer, along with strong natural selective forces have led to multi-drug resistant strains of S. aureus and many other pathogenic bacteria.[27] Horizontal gene transfer also plays a role in the spread of virulence factors, such as exotoxins and exoenzymes, amongst bacteria.[1] A prime example concerning the spread of exotoxins is the adaptive evolution of Shiga toxins in E. coli through horizontal gene transfer via transduction with Shigella species of bacteria.[36] Strategies to combat certain bacterial infections by targeting these specific virulence factors and mobile genetic elements have been proposed.[7] For example, horizontally transferred genetic elements play important roles in the virulence of E. coli, Salmonella, Streptococcus and Clostridium perfringens.[1]
Eukaryotes[edit]
"Sequence comparisons suggest recent horizontal transfer of many genes among diverse species including across the boundaries of phylogenetic'domains'. Thus determining the phylogenetic history of a species can not be done conclusively by determining evolutionary trees for single genes".[37]
- Analysis of DNA sequences suggests that horizontal gene transfer has occurred within eukaryotes from the chloroplast and mitochondrial genomes to the nuclear genome. As stated in the endosymbiotic theory, chloroplasts and mitochondria probably originated as bacterial endosymbionts of a progenitor to the eukaryotic cell.[38]
- Horizontal transfer occurs from bacteria to some fungi, especially the yeast Saccharomyces cerevisiae.[39]
- The adzuki bean beetle has acquired genetic material from its (non-beneficial) endosymbiont Wolbachia.[40] New examples have recently been reported demonstrating that Wolbachia bacteria represent an important potential source of genetic material in arthropods and filarialnematodes.[41]
- Mitochondrial genes moved to parasites of the Rafflesiaceae plant family from their hosts [42][43] and from chloroplasts of a not-yet-identified plant to the mitochondria of the bean Phaseolus.[44]
- Striga hermonthica, a eudicot, has received a gene from sorghum (Sorghum bicolor) to its nuclear genome.[45] The gene is of unknown functionality.
- Pea aphids (Acyrthosiphon pisum) contain multiple genes from fungi.[46][47] Plants, fungi and microorganisms can synthesize carotenoids, but torulene made by pea aphids is the only carotenoid known to be synthesized by an organism in the animal kingdom.[46]
- The malaria pathogen Plasmodium vivax acquired genetic material from humans that might help facilitate its long stay in the body.[48]
- A bacteriophage-mediated mechanism transfers genes between prokaryotes and eukaryotes. Nuclear localization signals in bacteriophage terminal proteins (TP) prime DNA replication and become covalently linked to the viral genome. The role of virus and bacteriophages in HGT in bacteria, suggests that TP-containing genomes could be a vehicle of inter-kingdom genetic information transference all throughout evolution.[49]
- HhMAN1 is a gene in the genome of the coffee borer beetle (Hypothenemus hampei) that resembles bacterial genes, and is thought to be transferred from bacteria in the beetle's gut.[50][51]
- A gene that allowed ferns to survive in dark forests came from the hornwort, which grows in mats on streambanks or trees. The neochrome gene arrived about 180 million years ago.[52]
- Plants are capable of receiving genetic information from viruses by horizontal gene transfer.[32]
- One study identified approximately 100 of humans' approximately 20,000 total genes which likely resulted from horizontal gene transfer,[53] but this number has been challenged by several researchers arguing these candidate genes for HGT are more likely the result of gene loss combined with differences in the rate of evolution [54]
Update: Genome Biol. 2015 Mar 13;16(1):50. doi: 10.1186/s13059-015-0607-3. Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Crisp A, Boschetti C, Perry M, Tunnacliffe A, Micklem G. http://www.ncbi.nlm.nih.gov/pubmed/25785303
Artificial horizontal gene transfer[edit]
Before it is transformed a bacterium is susceptible to antibiotics. A plasmid can be inserted when the bacteria is under stress, and be incorporated into the bacterial DNA creating antibiotic resistance. When the plasmids are prepared they are inserted into the bacterial cell by either making pores in the plasma membrane with temperature extremes and chemical treatments, or making it semi permeable through the process of electrophoresis, in which electric currents create the holes in the membrane. After conditions return to normal the holes in the membrane close and the plasmids are trapped inside the bacteria where they become part of the genetic material and their genes are expressed by the bacteria.
Genetic engineering is essentially horizontal gene transfer, albeit with synthetic expression cassettes. TheSleeping Beauty transposon system[55] (SB) was developed as a synthetic gene transfer agent that was based on the known abilities of Tc1/mariner transposons to invade genomes of extremely diverse species.[56] The SB system has been used to introduce genetic sequences into a wide variety of animal genomes.[57][58]
Importance in evolution[edit]
See also: Horizontal gene transfer in evolution
Horizontal gene transfer is a potential confounding factor in inferring phylogenetic trees based on the sequenceof one gene.[59] For example, given two distantly related bacteria that have exchanged a gene a phylogenetic treeincluding those species will show them to be closely related because that gene is the same even though most other genes are dissimilar. For this reason it is often ideal to use other information to infer robust phylogenies such as the presence or absence of genes or, more commonly, to include as wide a range of genes for phylogenetic analysis as possible.
For example, the most common gene to be used for constructing phylogenetic relationships in prokaryotes is the16s rRNA gene since its sequences tend to be conserved among members with close phylogenetic distances, but variable enough that differences can be measured. However, in recent years it has also been argued that 16s rRNA genes can also be horizontally transferred. Although this may be infrequent the validity of 16s rRNA-constructed phylogenetic trees must be reevaluated.[60]
Biologist Johann Peter Gogarten suggests "the original metaphor of a tree no longer fits the data from recent genome research" therefore "biologists should use the metaphor of a mosaic to describe the different histories combined in individual genomes and use the metaphor of a net to visualize the rich exchange and cooperative effects of HGT among microbes."[24] There exist several methods to infer such phylogenetic networks.
Using single genes as phylogenetic markers, it is difficult to trace organismal phylogeny in the presence of horizontal gene transfer. Combining the simple coalescence model of cladogenesis with rare HGT horizontal gene transfer events suggest there was no single most recent common ancestor that contained all of the genes ancestral to those shared among the three domains of life. Each contemporary molecule has its own history and traces back to an individual molecule cenancestor. However, these molecular ancestors were likely to be present in different organisms at different times."[61]
Scientific American article (2000)[edit]
Uprooting the Tree of Life by W. Ford Doolittle (Scientific American, February 2000, pp 90–95)[62] contains a discussion of the Last Universal Common Ancestor and the problems that arose with respect to that concept when one considers horizontal gene transfer. The article covers a wide area — the endosymbiont hypothesis for eukaryotes, the use of small subunit ribosomal RNA (SSU rRNA) as a measure of evolutionary distances (this was the field Carl Woese worked in when formulating the first modern "tree of life", and his research results with SSU rRNA led him to propose theArchaea as a third domain of life) and other relevant topics. Indeed, it was while examining the new three-domain view of life that horizontal gene transfer arose as a complicating issue: Archaeoglobus fulgidus is cited in the article (p. 76) as being an anomaly with respect to a phylogenetictree based upon the encoding for the enzyme HMGCoA reductase — the organism in question is a definite Archaean, with all the cell lipids and transcription machinery that are expected of an Archaean, but whose HMGCoA genes are actually of bacterial origin.[62]
Again on p. 76, the article continues with:
-
"The weight of evidence still supports the likelihood that mitochondria in eukaryotes derived from alpha-proteobacterial cells and that chloroplasts came from ingested cyanobacteria, but it is no longer safe to assume that those were the only lateral gene transfers that occurred after the first eukaryotes arose. Only in later, multicellular eukaryotes do we know of definite restrictions on horizontal gene exchange, such as the advent of separated (and protected) germ cells."
[62]
The article continues with:
-
"If there had never been any lateral gene transfer, all these individual gene trees would have the same topology (the same branching order), and the ancestral genes at the root of each tree would have all been present in the last universal common ancestor, a single ancient cell. But extensive transfer means that neither is the case: gene trees will differ (although many will have regions of similar topology)
and there would never have been a single cell that could be called the last universal common ancestor.
[62]
-
"As Woese has written, 'the ancestor cannot have been a particular organism, a single organismal lineage. It was communal, a loosely knit, diverse conglomeration of primitive cells that evolved as a unit, and it eventually developed to a stage where it broke into several distinct communities, which in their turn became the three primary lines of descent (bacteria, archaea and eukaryotes)' In other words, early cells, each having relatively few genes, differed in many ways. By swapping genes freely, they shared various of their talents with their contemporaries. Eventually this collection of eclectic and changeable cells coalesced into the three basic domains known today. These domains become recognisable because much (though by no means all) of the gene transfer that occurs these days goes on within domains."
[62]
With regard to how horizontal gene transfer affects evolutionary theory (common descent, universal phylogenetic tree) Carl Woese says:
-
"What elevated common descent to doctrinal status almost certainly was the much later discovery of the universality of biochemistry, which was seemingly impossible to explain otherwise. But that was before horizontal gene transfer (HGT), which could offer an alternative explanation for the universality of biochemistry, was recognized as a major part of the evolutionary dynamic. In questioning the doctrine of common descent, one necessarily questions the universal phylogenetic tree. That compelling tree image resides deep in our representation of biology. But the tree is no more than a graphical device; it is not some a priori form that nature imposes upon the evolutionary process. It is not a matter of whether your data are consistent with a tree, but whether tree topology is a useful way to represent your data. Ordinarily it is, of course, but the universal tree is no ordinary tree, and its root no ordinary root. Under conditions of extreme HGT, there is no (organismal) "tree." Evolution is basically reticulate."
[63]
In a May 2010 article in Nature, Douglas Theobald[64] argued that there was indeed one Last Universal Common Ancestor to all existing life and that horizontal gene transfer has not destroyed our ability to infer this.
Genes[edit]
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There is evidence for historical horizontal transfer of the following genes:
- Lycopene cyclase[disambiguation needed] for carotenoid biosynthesis, between Chlorobi and Cyanobacteria.[65]
- TetO gen conferring resistance to tetracycline, between Campylobacter jejuni.[66]
- Neochrome, gene in some ferns that enhances their ability to survive in dim light. Believed to have been acquired from algae sometime during the Cretaceous.[67]