Horizontal gene transfer/Citable Version

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

Horizontal gene transfer (HGT) (also called lateral gene transfer (LGT)) is any process in which an organism transfers genetic material to another cell or organism that is not one of its own offspring. HGT is thus very different from common vertical gene transfer which involves simple inheritance of parental traits by the progeny as part of the normal organism's life cycle, be it a sexual fusion of gametes to form zygotes as in animals and plants, or asexual propagation as in microorganisms such as bacteria and fungi. HGT occurs at a lower frequency than vertical gene transfer, so is not easily detected directly; its discovery depends on using special techniques to enable rare genetic events to be detected or inferred.

Introduction

The advent of genome science and bioinformatics has provided abundant indirect evidence that extensive natural HGT occurs between diverse biological taxa that are widely separated in the phylogenetic tree. About 2% of core microbial genes arise from HGT, and this allows the the main lineages of microbial evolution to be treated as trees with HGT cobwebs (see figures). These transfers include gene movement between different microbial species and other microbial taxa such as protists, 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 bits of genetic information, leaving the traditional tree of life intact. From: Comparing Gene Trees and Genome Trees: A Cobweb of Life? PLoS Biol 3 e347

Gene transfers between different biological domains, such as between eukaryotic protists and bacteria , or between bacteria and insects are the most phylogenetically extreme cases of HGT. Bacterial "rol" genes from Agrobacterium species have for instance been found in plants of the tobacco (Nicotiniana) genus. .

HGT is closely connected with mobile DNA ("jumping genes", transposons) and the dynamic changes that occur during genome evolution caused by the DNA rearrangement and transposition processes catalyzed by mobile DNA. Movement of mobile genes (such as transposons) within a genome, and between different parts of an organism's genome (that is, between the chromosomes of the nucleus, the circular mitochondrion chromosome , and the circular plastid (chloroplast) chromosome) are part of the mechanisms that enable horizontal gene transfer 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. The frequent discovery of shared DNA sequences such as the marinerclass 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. Close relatives 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 PLoS Biol 4(1) e35. A genome-wide analysis of millet and rice revealed clear 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 responsible for infectious multiple-antibiotic resistance in pathogenic bacteria, a major factor limiting the effectiveness of antibiotics. Inter-domain transfer of several genes, from the eukaryote domain to the bacterial domain for instance, as represented by an "accidentally pathogenic" bacterium (Legionella pneumophila, see illustration) that resides and replicates within a vacuole of protist and mammalian macrophage cells, has also been demonstrated .
• HGT is common in diverse groups of unicellular protists, which often 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' .

• Mechanisms for HGT in flowering plants involving parasitic plants such as dodder or endophytes such as mosses (which facilitate inter-species gene transfer by being in intimate cell-to-cell contact with their host plants) are now well established (see Horizontal gene transfer in plants).

• Not all of the vehicles by which HGT occurs are fully characterized, but some are clearly identified. HGT is difficult to detect directly, as it occurs at lower frequencies than with normal sexual reproduction within the species. Modern techniques of DNA analysis, by providing detailed comparison of genomes, provide much of the evidence for HGT. In insects, mites and viruses are probable 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 Horizontal gene transfer in prokaryotes

The three main mechanisms of HGT in bacteria and archaea which this article discusses 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

Protists

Analysis of the complete genome sequence of the protist Entamoeba histolytica indicates 96 cases of relatively recent horizontal gene transfer from prokaryotes , whereas similar analysis of the complete genome sequence of the protist "Cryptosporidium parvum" reveal 24 candidates of horizontal gene transfer from bacteria .There is convincing evidence also 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, the yeast Saccharomyces cerevisiae and Ashbya gossypii, has revealed that baker's yeast 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.

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.

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

Animals

Junk DNA is the most obvious general evidence of HGT in eukaryotes. Such seemingly non-functional repetitive DNA contitutes 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 horizontally transferred 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

Evolutionary theory

"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."

HGT is thus a potential confounding factor in inferring phylogenetic trees based on the sequence of one gene. For example, given two distantly related bacteria that have exchanged a gene, a phylogenetic tree including those species will show them to be closely related because that gene is the same, even though most other genes have diverged substantially. For this reason it is often ideal to use other information to infer phylogenies, such as the presence or absence of genes, or, more commonly, to include as wide a range of genes for analysis as possible.

The most common gene to be used for constructing phylogenetic relationships in prokaryotes is the small subunit ribosomal RNA (SSU rRNA, 16s rRNA) gene, since its sequences tend to be conserved among members with close phylogenetic distances, but variable enough that differences can be measured . The small subunit ribosomal RNA as a measure of evolutionary distances was pioneered by Carl Woese when formulating the first modern "tree of life", and his research results with SSU rRNA led him to propose the Archaea as a third domain of life.) However, recently it has been argued that small subunit ribosomal RNA genes can also be horizontally transferred. Although this may be rare, this possiblity is forcing scrutiny of the validity of phylogenetic trees based on these small subunit ribosomal RNAs.

Which metaphor: tree, a net or cobweb?

In his article Uprooting the Tree of Life, W. Ford Doolittle discusses the Last Universal Common Ancestor - the root of the Tree of Life - and the problems with that concept posed by HGT. He describes the microorganism Archaeoglobus fulgidus as an anomaly with respect to a phylogenetic tree based upon the code for the enzyme HMGCoA reductase - the organism is definitely an archaean, with all the cell lipids and transcription machinery expected of an archaean, but its HMGCoA genes are of bacterial origin. In the article, Doolittle says that while it is now widely accepted from the wight of evidence that mitochondria in eukaryotes derived from alpha-proteobacterial cells and that chloroplasts came from ingested cyanobacteria,

".. 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...

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..."

Doolittle suggested that the universal common ancestor cannot have been one particular organism, but was a loosely knit, diverse conglomeration of primitive cells that evolved together. These early cells, each with relatively few genes, differed in many ways, and swapped their genes freely. Eventually, from these eclectic cells came the three domains of life as we know them today: bacteria, archaea and eukaryote. These domains are now recognizably distinct because much of the gene transfer that still occurs is within these domains, rather than between them. Biologist Peter Gogarten reinforced these arguments, and suggested that the metaphor of a tree does not fit the data from recent genome research, and that biologists should instead 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."

Resolution of uncertainty with Phylogenomics

Tree Based on the Median Tree Algorithm. Ge F et al The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer PLoS Biol 3(10), e316. Branches with bootstrap (statistical) scores less than 50% were collapsed. Three domains of life are shown as (A) archaea, (B–J) bacteria, and (K) eukaryote. Species are labeled with different colors based on their inferred HGT rates: red, >4%; yellow, 3%–4%; pink, 2%–3%; blue, 1%–2%; green, <1%. Taxonomy labels are (A) Euryarchaea, (B) Proteobacteria, (C) Chlamydiae, (D) Spirochaetes, (E) Thermotogae, (F) Aquificae, (G) Actinobacteria, (H) Deinococcus, (I) Cyanobacteria, (J) Firmicutes, and (K) Fungi.

Despite the uncertainties in reconstructing phylogenies back to the beginings of life, progress is being made in reconstructing the tree of life in the face of uncertainties raised by HGT. The uncertainty of any inferred phylogenetic tree based on a single gene can be resolved by using several common genes or even evidence from whole genomes . One such approach, sometimes called 'multi-locus typing', has been used to deduce phylogenic trees for organisms that exchange genes, such as meningitis bacteria.

Jonathan Eisen and Claire Fraser have pointed out that:

"In building the tree of life, analysis of whole genomes has begun to supplement, and in some cases to improve upon, studies previously done with one or a few genes. For example, recent studies of complete bacterial genomes have suggested that the hyperthermophilic species are not deeply branching; if this is true, it casts doubt on the idea that the first forms of life were thermophiles. Analysis of the genome of the eukaryotic parasite Encephalitozoon cuniculi supports suggestions that the group Microsporidia are not deep branching protists but are in fact members of the fungal kingdom. Genome analysis can even help resolve relationships within species, such as by providing new genetic markers for population genetics studies in the bacteria causing anthrax or tuberculosis. In all these studies, it is the additional data provided by a complete genome sequence that allows one to separate the phylogenetic signal from the noise. This is not to say the tree of life is now resolved— we only have sampled a smattering of genomes, and many groups are not yet touched"

These whole genome approaches are enabling estimates of the relative frequency of HGT and the relative low values being observed suggests that the tree model is still a valid metaphor for evolution - but adorned with cobwebs of horizontally transferred genes. This is the main conclusion of a 2005 study of more than 40 complete microbial genomic sequences by Fan Ge, Li-San Wang, and Junhyong Kim. They estimate the frequency of HGT events at about 2% of core genes per genome by using a novel statistical method to compare the gene trees and whole-genome trees of these 40 microbes..

See also

• Gene flow
• Phylogenetic tree
• Endogenous retrovirus
• Germline
• Mitochondrion
• Integron
• Provirus
• Retrotransposon
• Mobile DNA
• Pilus

References

Further Reading

• 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: Salzberg SL et al (2001) Microbial genes in the human genome: lateral transfer or gene loss?" Science 292:1903-6 [1]
• Discussion of both the evolutionary and ecological activities of viruses in the ocean, a major source of HGT in nature: Weinbauer MG, Rassoulzadegan F (2004) Are viruses driving microbial diversification and diversity? Envir Microbiol 6:1-11 doi: 10.1046/j.1462-2920.2003.00539.x
• This article shifts the emphasis in early phylogenic adaptation from vertical to horizontal gene transfer. Woese C (2002) On the evolution of cells PNAS USA 99:8742-7
• Convincing evidence of horizontal transfer of bacterial DNA: Hall C et al (2005) Contribution of horizontal gene transfer to the evolution of "Saccharomyces cerevisiae" Eukaryot Cell 4:1102-15
• Book with a comprehensive discussion of mobile DNA, jumping genes, transposons etc in many organisms, not only bacteria. Berg DE, Howe MM (Eds.)(1989) "Mobile DNA". American Society for Microbiology. Washington D.C.
• Proposal for using the presence or absence of a set of genes to infer phylogenies, in order to avoid confounding factors such as HGT. Snel B et al (1999) Genome phylogeny based on gene content Nature Genetics 21:66-7 [2]
• A comprehensive treatise: Syvanen M, Kado CI (2002) Horizontal Gene Transfer 2nd edition, Academic Press ISBN 0-12-680126-6

External links

• Webfocus in Nature with free access review articles Focus on horizontal gene transfer
• (1999) Horizontal gene transfer among genomes: The complexity hypothesis PNAS USA 96:3801-6
• Ochman H et al (2000) Lateral gene transfer and the nature of bacterial innovation (pdf)
• The New Yorker July 12, 1999, p44-61 "Smallpox knows how to make a mouse protein. How did smallpox learn that? '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'"
• Retrotransfer or gene capture: a feature of conjugative plasmids, with ecological and evolutionary significance
• Horizontal Gene Transfer - A New Paradigm for Biology
• Horizontal Gene Transfer (p334 of Molecular Genetics by Ulrich Melcher)
• Report on horizontal gene transfer by Mae-Wan Ho, 1999
• Recent Evidence Confirms Risks of Horizontal Gene Transfer
• Horizontal Gene Transfer at sciences.sdsu.edu