Horizontal gene transfer/Citable Version

Legionella pneumophila are prokaryotic bacteria that can survive and reproduce inside phagocytic cells such as protists that have eaten them. They are competent in DNA transformation and occasionally capture genes from their eukaryotic host cells.

Horizontal gene transfer occurs when an organism transfers its genetic material to a being other than one of its own offspring. The actual process of this transfer can be by any mechanism, but since genes are not passing by descent, HGT is always very different from vertical gene transfer. In vertical descent, parental traits are inherited by progeny by one of two general methods: either (1) sexual reproduction in which gametes form zygotes, a common method in higher animals and plants, or (2) by asexual reproduction, where splitting of cells or growth of an entire organism from a fragment, occurs, as usual in microorganisms such as bacteria and fungi, and also occurs in some animals and plants. Horizontal Gene Transfer (abbreviated as HGT) is a much more recently discovered route of passage for genetic material. Through HGT, genetic material can be shared between organisms without the immediate relatedness of mother cell to daughter cells, or parent organisms to offspring, but may not even be of the same species, genus or kingdom (put that in temporarily) of life form. Horizontal gene transfer (sometimes called lateral gene transfer) occurs between cells at such a markedly lower frequency than vertical gene transfer that its detection requires special techniques.

Introduction

Evidence from genome science and bioinformatics shows that HGT has occurred naturally between diverse biological taxa that are widely separated in the phylogenetic tree of life. Known horizontal gene transfers include movement of genetic material between different species of microbes and other microbial taxa such as protists, gene movement between different plant families, between different animals, and between bacteria and plants.

HGT — gene exchange between non-related organisms —appears commonplace among bacteria, but contributes just small fragments of genetic information, leaving the traditional tree of life intact. From: [http://biology.plosjournals.org/perlserv/?request=slideshow&type=figure&doi=10.1371/journal.pbio.0030347&id=36052 Comparing Gene Trees and Genome Trees: A Cobweb of Life? PLoS Biology 3 e347]

Microorganisms appear to be most affected by HGT, but research suggests that even in microbes only about 2% of core genes are transferred laterally - a low enough percentage to allow the the main lineages of microbial evolution to be treated as 'trees' branched by vertical descent, HGT included in the scheme only as 'cobwebs' (see figure to right).

Gene transfers between different biological sub-kingdoms (domains), such as between eukaryotic protists and bacteria , or between bacteria and insects are the most phylogenetically extreme cases of HGT. An example is bacterial 'rol' genes from Agrobacterium species which have been found in tobacco plants (Nicotiniana). .

HGT is just one of the processes causing rearrangement of genomes during evolution. The possibility of intracellular movement of genes between different parts of an organism's genome (that is, between the chromosomes of the nucleus, the circular mitochondrion chromosome, or the circular plastid (chloroplast) chromosome) need to be considered when evaluating HGT between different species.

Main features of HGT in nature

• A hallmark of HGT is the presence of the same gene in organisms that are only very distantly related to each other. The frequent discovery of shared DNA sequences such as the mariner class of transposons, insertion sequence DNA, and retrovirus genes in diverse species, and shared mitochondrial genes in diverse flowering plants, indicate that mobile DNA has natural pathways for movement between species. (The name mariner for a class of related transposons is an allusion to The Rime of the Ancient Mariner, meaning a traveller to distant lands.) Close relatives of mariner mobile DNA have been discovered in organisms as diverse as mites, flatworms, hydras, insects, nematodes, mammals and humans.

Millet. From: Jumping Genes Cross Plant Species Boundaries. Analysis of the genomes of millet and rice revealed evidence for HGT between chromosomes in the nucleus of one plant to chromosomes in the nucleus of a reproductively isolated species

• Horizontal movement of genes is common among bacteria, and is a major factor in accelerating the rate of evolution in these organisms. HGT is involved in infectious multiple-antibiotic resistance in pathogenic bacteria, a major factor limiting the effectiveness of antibiotics. Inter-domain (sub-kingdom) transfer of several genes from eukaryotes to bacteria for instance, has occurred in the 'accidentally pathogenic' bacterium (Legionella pneumophila, see illustration) that lives and replicates within a vacuoles of protist and mammalian macrophage cells.

• HGT is documented in diverse unicellular protists, which can contain several genes transferred from both prokaryotes and other protists.

• HGT occurs globally on a massive scale among marine microorganisms, and viruses, at total numbers near 10²⁹ being the most common biological entities in the sea, are a major pathway for inter-species gene movement in the ocean. The estimated virus-mediated gene transfer events in the Mediterranean sea are 10¹³ per year. Endosymbiosis with an alga is identified as a route for HGT in marine dinoflagellates, the organisms that cause 'red tides'.

• Interspecies gene movement within the same biological genus by cross-hybridization is common in flowering plants. Mechanisms for HGT in flowering plants between more distant taxa involving parasitic plants such as dodder and endophytes such as mosses (which facilitate inter-species gene transfer by being in intimate cell-to-cell contact with their host plants) are also well established (see Horizontal gene transfer in plants). Plant mitochondria are unusually active in HGT.

• Not all of the vehicles by which HGT occurs are fully characterized, but some have been identified. HGT is hard to detect directly, as it occurs at lower frequencies than with normal sexual reproduction within the species, but modern techniques of DNA analysis, by providing detailed comparison of genomes, provide much of the evidence for HGT. In insects, mites and viruses are probably vectors for HGT. In bacteria, surface appendages called pili have various roles in DNA uptake, DNA secretion and DNA transfer which have been extensively analyzed; HGT in bacteria includes plasmid-mediated promiscuous mating by bacteria, for instance by the crown-gall bacterium Agrobacterium tumefaciens, and carriage of genes between species by viruses. Direct DNA uptake as another transfer mechanism is illustrated by Legionella bacteria, which are naturally competent for DNA uptake.

Prokaryotes

See main article HGT in prokaryotes

The three main mechanisms of HGT in bacteria and archaea discussed here are:

• Bacterial Transformation or direct uptake of extracellular DNA.
• Transduction of genes by bacterial viruses.
• Bacterial conjugation, a gene transfer process carried out by plasmids and conjugative transposons.

Eukaryotes

See also Endosymbiotic theory

Protists

Analysis of the complete genome sequence of the protist Entamoeba histolytica indicates 96 cases of relatively recent HGT from prokaryotes , whereas similar analysis of the protist Cryptosporidium parvum reveals 24 candidates of HGT from bacteria .There is also convincing evidence that a bacterial gene for a biosynthetic enzyme has been recruited by the protist Trichomonas vaginalis from bacteria related to the ancestors of Pasteurella bacteria. These results fit the idea that "you are what you eat". That is, with unicellular grazing organisms, foreign genetic material is constantly entering the cell and occasionally the genome from food organisms

Fungi

Comparison of the genome sequences of two fungi, baker's yeast (Saccharomyces cerevisiae) and Ashbya gossypii, has shown that Saccharomyces has received two genes from bacteria by HGT. One codes for an enzyme that allows baker's yeast to make pyrimidine nucleotide bases anaerobically, and the other allows usage of sulfur from several organic sulfur sources. Other work with yeasts suggests that eight genes from Yarrowia lipolytica, five from Kluyveromyces lactis, and one from Debaryomyces hansenii are horizontally transferred.

Other eukaryotes

Analysis of DNA sequences suggests that HGT has also occurred within multicellular eukaryotes, by a route that involves transfer of genes from chloroplast and mitochondrial genomes to the nuclear genomes. According to the endosymbiotic theory, chloroplasts and mitochondria originated as the bacterial endosymbionts of a progenitor to the eukaryotic cell, and endosymbiosis can be considered to be a special case of HGT.

Plants

See Horizontal gene transfer in plants for

• Natural gene transfer between plants that do not cross-pollinate
• Jumping genes cross naturally between rice and millet
• Epiphytes and parasites as a bridge for gene flow between diverse plant species

See Transgenic plant for hybridization by cross-pollination and artificial horizontal gene transfer in biotechnology.

It has also been discovered that plant genes can move to endophyte fungi that grow on them. Several plant endophyte fungi that grow on taxol-producing yew trees have gained the ability to make taxol themselves . (Taxol, also called paclitaxel, is an anti-cancer drug found in yew trees.)

Animals

Junk DNA is the most obvious general evidence of HGT in eukaryotes. Such seemingly non-functional repetitive DNA is a major portion of many genomes of plants and animals. This DNA usually includes multiple copies of various 'Jumping genes' which can proliferate within a genome after they have been transferred from another species. Examples in the human of such mobile elements are 'Hsmar1' and 'Hsmar2' which are related to the widely studied 'mariner' transposon. Close relatives of mariner mobile DNA have been discovered in organisms as diverse as mites, flatworms, hydras, insects, nematodes, mammals and humans. Retroviruses and retrotransposons are other examples of mobile horizontally transferred DNA found in animals.

The adzuki bean beetle Callosobruchus chinensis is infected with several strains of bacterial Wolbachia endosymbionts. A genome fragment of one of these endosymbionts has been found transferred to the X chromosome of the host insect.

History of discovery of HGT

See main article Horizontal gene transfer (History)

• Bacterial genetics starts in 1946

see main article Horizontal gene transfer in prokaryotes

• First glimpses of horizontal transfer of traits in plant evolution

see also main article Barbara McClintock

• Discovery of mobile genes in flies, and mariner
• HGT and genetic engineering

Decoding the tree of life from genomes scrambled by HGT

Because each organism carries a record of its ancestry in its DNA, methods for rapid gene isolation and analysis of DNA encoded sequences - which can extract the information from this ancestral archive - have been powerful tools for answering questions about evolution. These techniques have enabled rapid expansion of the field of biological systematics known as phylogenetic inference. Comparison of related (homologous) gene sequences from different organisms has made it possible to reconstruct the history of many evolutionary lineages. Many issues about evolution have been clarifed by comparing homologous genes from different species, genera, families, and phyla. Unfortunately, HGT complicates the picture, because HGT 'scrambles' the evidence needed to deduce the branching patterns of evolutionary trees, and requires coalescence of branches in tree representations of evolution. One area of current research in phylogenetic inference, and arguably one the most challenging problems in evolutionary theory, is the early stages in the evolution of life. This quandary about the origins of different cell types provides a good illustration of the complications introduced by HGT into the reconstruction of evolutionary history.

The main early branches of the tree of life have been intensively studied by microbiologists because the first organisms were microorganisms. A gene very commonly used for constructing phylogenetic relationships in microrganisms is the small ribosomal subunit ribosomal RNA gene (SSU rRNA) gene, as its sequences tend to be conserved among members with close phylogenetic distances, yet it is variable enough that differences can be measured. The SSU rRNA as a measure of evolutionary distances was pioneered by Carl Woese when formulating the first modern "tree of life", and his results led him to propose the Archaea as a third domain (sub-kingdom) of life.

A three domain tree of life showing the separation of Bacteria, Archaea, and Eukaryote domains. See Microorganisms article for further explanation

Microbiologists introduced the term domain for the three main early branches of the tree of life, where domain is a phylogenetic term very similar in meaning to biological kingdom. These represent the three main lineages in evolution of early cellular life, and are currently represented by the Bacteria, the Archaea (single celled organisms superficially similar to bacteria), and Eukarya (eukaryote) domains. Eukaryotes are all organisms with a well defined nucleus, and this domain comprises protists, fungi, and all organisms in the animal and plant kingdoms, including humans. As seen in the figure (left), studies of SSU rRNA genes (and some other genes) might suggest that Archaea and Eukarya have a sister relationship in evolution, and it has often been assumed that eukaryotes evolved from archeal cells. However, the fact that genes can move between distant branches of the tree of life even at low probabilities poses problems for scientists trying to reconstruct evolution from studying genes and gene sequences in different organisms due to the scrambling effect of HGT. The challenges are most awkward for the ambitious reconstruction of the earliest branches of the tree of life - because over a long enough time and with large numbers of organisms, many HGT events are certain to have occurred even though each particular transfer event has a low probability.

Thus recent discoveries of 'rampant' HGT in microorganisms, and the detection of horizontal movement of even genes for SSU rRNA have forced biologists to question the accuracy of at least the early branches in the tree of life, and even question the validity of trees as useful models of microbial evolution.

Recent efforts to infer evolutionary trees while recognizing HGT

Hypothesis for the origin of eukaryotic (nucleated) cells, from fusion of two distinct non-nucleated prokaryotes that were partners of a postulated ancient symbiosis.

The challenges of acertaining an accurate branching structure for evolutionary trees of microbes, especially the earliest branches in the tree of life, have been a great spur for current biological research. Clear answers to important questions about these trees are not yet available, but many interesting discoveries and ideas are emerging.

Instead of relying a single gene such as the SSU rRNA gene to reconstruct evolution, scientific effort has shifted to exploiting the comprehensive information from the many complete genome sequences of organisms that are now available.

So far, this comparitive genomics approach, made possible by specially developed computer programs and mathematical algorithms, suggests that most of the core genes of bacteria that are useful for deducing evolutionary histories are unaffected by HGT. This indicates that reliable trees can still be deduced for a least the more recent stages in microbial evolution, such as evolutionary relationships within particular bacterial phyla, provided that many genes are used to investigate how lineages are related to one another. Thus it is argued that the 'tree' is still a valid metaphor for microbial evolution - but a tree adorned with 'cobwebs' of horizontally transferred genes.

But it is also clear that trees based only on SSU rRNA alone do not capture the events of early eukaryote evolution accurately, and the origins of the first nucleated cells are still uncertain. For instance, careful analysis of the complete genome of the eukaryote yeast shows that many of its genes are more closely related to bacterial genes than they are to archaea, and it is now clear that archaea were not the simple progenitors of the eukaryotes, in stark contradiction to the findings based on SSU rRNA and limited samples of other genes.

One controversial hypothesis coming out of recent computer-assisted studies of complete genome DNA sequences is that the first nucleated cell arose from two distinctly different ancient prokaryotic (non-nucleated) species that had formed a symbiotic relationship with one-another to carry out different aspects of metablism. One partner of this postulated symbiosis is proposed to be a true bacterial cell, and the other an archaean cell. It is postulated that this symbiotic partnership progressed to the cellular fusion of the partners to generate a chimeric or hybrid cell with a membrane bound internal structure that was the forerunner of the nucleus. The next stage in this scheme was transfer of both partner genomes into the nucleus and their fusion with one-another. Several variations on this chimera hypothesis for the origin of nucleated cells have been suggested, but other biologists dispute the proposal.

See also

• Gene flow
• Species
• Phylogenetic tree
• Endogenous retrovirus
• Germline
• Mitochondrion
• Endosymbiotic theory
• Integron
• Provirus
• Retrotransposon
• Mobile DNA
• Pilus
• Transgenic plant

References

Further Reading

• Horizontal Gene Transfer Syvanen M, Kado CI (2002) 2nd edition, Academic Press ISBN 0-12-680126-6 A comprehensive treatise. Reviewed here by M-W Ho

• Acquiring genomes: a theory of the origin of species. Margulis L and Sagan D (2002) Basic Books ISBN 0-465-04392-5. A book that looks at gene transfer from a different perspective to many conventional interpretations, but with an interesting emphasis on microbial diversity. Reviewed here.

• Where Do All Those Genes Come From? This study resolves a long-standing paradox: how is it possible to deduce reliable evolutionary histories from gene sequences in bacteria despite extensive HGT?

• Richardson AO, Palmer, JD (2007) Horizontal gene transfer in plants. Journal of Experimental Botany 58:1–9 doi:10.1093/jxb/erl148 PMID 17030541

• Gogarten JP Townsend JP (2005) Horizontal gene transfer, genome innovation and evolution. Nat Rev Microbiol 9:679-87 PMID 16138096. One article in a whole issue of the journal Nature Reviews Microbiology largely devoted to HGT.

• Mobile DNA. Berg DE, Howe MM (Eds.)(1989) American Society for Microbiology. Washington D.C. ISBN 1-55581-005-5 Book with a comprehensive discussion of mobile DNA, jumping genes, transposons etc in many organisms, not only bacteria. Reviewed by Freeling M (1990) in Q Rev Biol 65:217-8

• Salzberg SL et al. (2001) Microbial genes in the human genome: lateral transfer or gene loss? Science 292:1903-6 PMID 11358996. This reports that one dramatic claim of HGT - in which a distinguished group of scientists claimed that bacteria transferred their DNA directly into the human lineage - was simply wrong [1]

• Weinbauer MG, Rassoulzadegan F (2004) Are viruses driving microbial diversification and diversity? Envir Microbiol 6:1-11 PMID 14686936 Discussion of both the evolutionary and ecological activities of viruses in the ocean, a major source of HGT in nature.

• Woese C (2002) On the evolution of cells. Proc Natl Acad Sci USA 99:8742-7 PMID 12077305 This article shifts the emphasis in early phylogenic adaptation from vertical to horizontal gene transfer.

• Hall C et al. (2005) Contribution of horizontal gene transfer to the evolution of Saccharomyces cerevisiae. Eukaryot Cell 4:1102-15 PMID 15947202 Convincing evidence of horizontal transfer of bacterial DNA into yeast.

• Snel B et al. (1999) Genome phylogeny based on gene content. Nature Genetics 21:66-7 PMID 9916801 Proposal for using the presence or absence of a set of genes to infer phylogenies, in order to avoid confounding factors such as HGT.

External links

• Focus on horizontal gene transfer Webfocus in Nature with free access review articles
• Horizontal gene transfer (p334 of Molecular Genetics by Ulrich Melcher).
• Horizontal gene transfer at sciences.sdsu.edu
• Smallpox knows how to make a mouse protein. How did smallpox learn that? The New Yorker July 12, 1999, p44-61 'The poxviruses are promiscuous at capturing genes from their hosts,' Esposito said. 'It tells you that smallpox was once inside a mouse or some other small rodent'
• Horizontal gene transfer among genomes: The complexity hypothesis. Proc Natl Acad Sci USA 96:3801-6 (1999)
• Lateral gene transfer and the nature of bacterial innovation (pdf), Ochman H et al (2000)
• Gogarten Laboratory Webpages.
• Horizontal gene transfer - A new paradigm for biology
• Report on horizontal gene transfer by Mae-Wan Ho, 1999
• Recent evidence confirms risks of horizontal gene transfer