horizontal gene transfer and the history of life

Horizontal Gene Transfer and the History of Life

Vincent Daubin1,2 and Gergely J. Szollosi3

1Laboratoire de Biometrie et Biologie Evolutive, Universite de Lyon, 69000 Lyon, France2Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5558, Universite Lyon 1,69622 Villeurbanne, France

3ELTE-MTA “Lendulet” Biophysics Research Group, 1117 Budapest, Hungary

Correspondence: [email protected]

Microbes acquire DNA from a variety of sources. The last decades, which have seen thedevelopment of genome sequencing, have revealed that horizontal gene transfer has been amajor evolutionary force that has constantly reshaped genomes throughout evolution.However, because the history of life must ultimately be deduced from gene phylogenies,the lack of methods to account for horizontal gene transfer has thrown into confusion the veryconcept of the tree of life. As a result, many questions remain open, but emerging method-ological developments promise to use information conveyed by horizontal gene transfer thatremains unexploited today.

The discovery of the existence of prokaryoticmicrobes dates back more than 300 years.

Since then, our picture of our distant micro-scopic relatives has undergone several revolu-tions: from being the living “proofs” of the ex-istence of spontaneous generation, they becamelater the “archaic” representatives of our distantancestors, to finally be legitimately recognizedas exceptionally diverse organisms, keystone toany ecosystem, including the most familiar andthe most hostile environments on Earth. Simi-larly, although they were first seen as elementaryand unbreakable bricks of life, they are now seenas genetically composite bodies, heavyweightchampions of “gene robbery.” The most recentof these revolutions has indeed been the reali-zation of their unparalleled ability to integrategenetic material coming from more or less evo-lutionarily distant organisms. This mechanismis called “horizontal gene transfer” as opposed

to vertical transmission from mother to daugh-ter cell.

MECHANISMS OF HORIZONTAL TRANSFER

Horizontal Gene Transfer and the Natureof Heredity

The first description of a horizontal gene trans-fer has been a major advance in molecularbiology, and can even be seen as its foundingexperiment. By demonstrating, in 1928, thatnonvirulent pneumococcus bacteria can be-come pathogenic simply by contact with viru-lent bacteria, even bacteria destroyed by heat,Griffith (1928) showed that there is a thermo-stable principle, capable of modifying heredity.This principle would be identified years later asDNA (Avery et al. 1944). This discovery, how-ever, could only take place because of the re-

Editor: Howard Ochman

Additional Perspectives on Microbial Evolution available at www.cshperspectives.org

Copyright # 2016 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a018036

Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018036

1

on April 11, 2022 - Published by Cold Spring Harbor Laboratory Press http://cshperspectives.cshlp.org/Downloaded from

mailto:[email protected]



http://www.cshperspectives.org



http://cshperspectives.cshlp.org/

markable ability of pneumococci to acquireDNA horizontally. We now know that in thisexperiment, a gene responsible for the synthesisof the polysaccharide capsule of the bacteriumis transferred, and incorporated in place of itsdeficient counterpart in nonvirulent strains.

The cytoplasm of the bacteria, wherein thegenome is located, is effectively isolated fromthe external medium by one or more mem-branes, depending on the groups of bacteria.DNA cannot passively traverse these obstacles.There are specific mechanisms that facilitateforeign DNA’s access to the genome. Three ofthese are well documented.

† Transformation is an active mechanism bywhich free DNA present in the medium, typ-ically derived from dead organisms and istaken up into the cytoplasm. This could bemainly for nutritional purposes, but somebacteria are very selective on the type ofDNA that they allow into the cell, suggestingthat it also serves to favor recombination withclose relatives (Redfield et al. 1997; Szollosiet al. 2006; Mell and Redfield 2014).

† Conjugation is a one-way transmissionmechanism of DNA from one cell to anothervia a “sexual pilus” by which DNA is trans-ported. This mechanism has spuriously beencompared with eukaryotic sex. The donorbacterium is described as male, whereas therecipient bacterium is called female. In fact,the genes responsible for conjugation arecarried by plasmids or bacteriophages knownas “conjugative,” that use conjugation to in-sure their transmission (and thus transformthe female into male). Sometimes, however,these conjugative elements accidentally carrywith them the DNA of the host, in which casethey can promote transfer of genes other thantheir own.

† Transduction is a type of transfer that occursvia a bacteriophage that transmits the DNAfrom one cell to another. At the end of itsreplication cycle, the host cell undergoes ly-sis, and fragmented DNA of the host genomeis occasionally packaged inside infectiousparticles. This DNA can then be injectedinto another individual, in place of virus

DNA. Some species of bacteria have hijackedthis mechanism to their advantage and haverecruited bacteriophage genes to facilitate ge-netic exchange. Such defective phage capsids,present, in particular, in many a-proteobac-teria, are called “gene transfer agents” (GTAs)(Lang and Beatty 2007).

Once inside the cytoplasm, DNA has severalpossible fates. It can be destroyed by DNA deg-radation systems that are present in the cyto-plasm of the host (restriction enzymes, DNAses,etc.) or persist as autonomous replicative enti-ties, such as plasmids. Finally, all or part ofthe DNA may be integrated into the host chro-mosome. This integration depends on severalfactors such as the degree of similarity withgenomic DNA of the host, in the case of homol-ogous recombination, or physical associationwith other sequences capable of integrationsuch as transposable elements or bacteriophagegenes. When homologous recombination oc-curs, the foreign DNA sequence replaces existinghomologous sequences in the host genome—this is what happens in the pneumococcus ex-ample. On the contrary, when DNA is integratedinto the genome by other means, it is often sim-ply inserted as an entirely new gene.

Evolutionary Consequences ofHorizontal Transfer

The true evolutionary role and impact that hor-izontal gene transfer has had on the evolutionof life were only realized recently with the ad-vent of genome sequencing. The above mecha-nisms have relatively low specificity, and thusallow movement of genetic information evenbetween distant species, with correspondinglyprofound consequences on the modes of adap-tation and the concept of bacterial species(Ochman et al. 2005).

In comparison to descent with modifica-tion, horizontal gene transfer offers the possi-bility for quite drastic adaptation. However, farfrom questioning the principle of Darwinianevolution, as has been suggested, this mode ofevolution underscores the importance of takinginto account different levels of selection (e.g.,genes vs. genomes) for understanding the evo-

V. Daubin and G.J. Szollosi

2 Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018036



lution of genomes. Many genes present in bac-terial genomes come from prophages and hencehave evolved under different constraints thanthe rest of the genome. Nonetheless, bacterialgenomes have repeatedly co-opted functionsfrom their genomic parasites (Canchaya et al.2004; Bobay et al. 2014). Also, it has been sug-gested that the organization in operons of bac-terial genomes (i.e., in groups of functionallyrelated genes and cotranscribed) could be theresult of a need for coregulation as well as aselection pressure for genes that interact to per-form a function to remain together duringhorizontal transfers. This model is known asthe “selfish operon” (Lawrence and Roth 1996;Price et al. 2006). Horizontal gene transfer hasalso been seen as a barrier to defining speciesin prokaryotes (and, as we shall see later, also forthe concept of prokaryotic phylogeny). Definedin animals on a criterion of interfertility, or on amore molecular level, by the limits of recombi-nation, the biological species is a concept that isdifficult to apply to bacteria.

INTRA- AND INTERSPECIFIC GENETICEXCHANGE

Better than Sex

In sexual eukaryotes, the theoretical advantagesof genetic exchange, through the elimination ofdeleterious mutations and the combination offavorable ones, are well established. Horizontalgene transfer provides the same advantageswhen the acquisition of DNA is from conspe-cifics, although recombination is not associatedwith reproduction. However, these movementsof genetic information extend well beyond thespecies boundaries. Many cases of horizontaltransfers have been described, particularly inconnection with the acquisition of new func-tions and colonization of new ecological niches.In particular, the capacity shown by some bac-terial strains of acquiring virulence genes orantibiotic resistance remains a major healthproblem. Yet, one can wonder whether thesecases are anecdotal, or if, instead, the horizontaltransfer is a mechanism that plays a key role inthe evolution of prokaryotes. Answering this

question involves detecting transfers betweenspecies, to quantify their importance.

The Many Facets of Horizontal Transfer

There are three major types of approaches toidentifying horizontal transfers in completelysequenced genomes:

1. Methods for comparison of gene repertoirescontrast genomes of related species or strainsof the same species and often reveal very dif-ferent gene content. These differences ingene repertoires are explained by gene losses(deletions) and/or gains. However, as in thecase of Escherichia coli, bacterial strains ofthe same species frequently have hundredsof genes that are strain specific. In such cases,we must either assume an ancestral genomeof astronomical size, to interpret these dif-ferences by genes losses, or accept that dif-ferences between closely related strains aremostly the result of recent integrations(Daubin et al. 2003a; Touchon et al. 2009).

2. Methods of gene composition analysis relyon the long-standing observation that thereis a great diversity of GþC content amongbacterial genomes (Sueoka 1962) and thateach genome has a base composition andcodon usage that can be diagnostic of thespecies. However, regions having contrast-ing nucleotide or codon composition areoften found in bacterial genomes. This sug-gests that such regions originate from recenttransfer from genomes having different com-positions (Lawrence and Ochman 1998;Ochman et al. 2000). As relatively closelyrelated organisms (such as enterobacteria-ceae, for example) have comparable GþCcontent, genes with diverging GþC con-tent are generally considered as originatingfrom more distant organisms. Overall, thesemethods are expected to underestimate thenumber of transfers, for two reasons. First,they are not able to identify transfers fromspecies having a composition similar to thehost genome. Second, these methods cannotfind ancient transfers, because these genes,once integrated, gradually acquire the char-


Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018036 3



acteristics of the host genome. It is worthnoting, although, that some mechanismsprobably maintain an heterogeneity ofGþC content of genes within bacterial ge-nomes, which could be deceiving for thesemethods (Guindon and Perriere 2001; Dau-bin and Perriere 2003; Lassalle et al. 2015).

3. Phylogenetic methods are the most general,and potentially most sensitive, methods forinferring horizontal transfers. These meth-ods reconstruct the history of a family ofhomologous genes (a gene tree), and com-pare it to a putative history of the species inwhich the genes are found (the species tree).Phylogenetically well-supported disagree-ments between the two trees can be inter-preted in terms of transfers. Such methodshave the advantage of providing informationon the donor species (not just the recipient)and can, in theory, identify ancient transfers.The difficulty of this approach is that it re-quires a reference phylogeny, and the abilityto differentiate between different types ofevents that can change the history of a genesuch as duplications, losses, and transfers(see Fig. 1). Most studies aimed at evaluatingthe role of gene transfer using phylogeneticapproaches have tried to circumvent the

problem of duplications and loss of genesby focusing on genes that are present in atmost one copy in each genome (Beiko et al.2005; Than et al. 2008; Abby et al. 2010, 2012;Puigbo et al. 2010). Only recently, new meth-ods have been developed that can sort out therole of duplication, transfer, and loss in genehistories (Bansal et al. 2012; Szollosi et al.2012, 2013b; Sjostrand et al. 2014). A cru-cial ingredient of any phylogenetic methodthat aims at detecting gene transfer is theability to account for phylogenetic uncer-tainty. Taking into consideration phyloge-netic uncertainty is important, because lim-ited signal leads to reconstruction errors thatsubsequently result in a gross overestimate ofthe amount of horizontal gene transfer. Toovercome this problem, it is possible to ex-ploit the fact that, although each homolo-gous gene family has its own unique story,they are all related by a shared species history,and this history can be helpful for genetree inference. In a study that attempted totake into account shared species history forgene tree reconstruction in cyanobacteria(Szollosi et al. 2013a), the majority of phy-logenetic discord was found to result fromreconstruction errors. This can be corrected

Deep coalescence

A B

Duplication/extinction

Horizontaltransfer

C D

A B C DA B

C

A B C D

dup

Figure 1. The processes of discord. Three biological processes can generate gene trees that differ from the speciestree. (A) The combined action of gene duplication and loss, (B) horizontal gene transfer, and (C) deepcoalescence, where polymorphic alleles can remain present in a population for a time than spans two speciations(black squares show the alleles that coexist for this period). In each of these examples, the genes from species Cand D are closest relatives, although species C is more closely related to species B (adapted from Maddison 1997).





by combining information from sequencealignment with information from a putativespecies tree and probabilities of duplication,transfer, and loss optimized across gene fam-ilies. The result is a striking reduction inapparent phylogenetic discord, with 24%,59%, and 46% reductions, respectively, inthe mean numbers of duplications, transfers,and losses per gene family.

More generally, the three approaches de-scribed above give seemingly very different ideasabout the impact of horizontal transfer on ge-nomes (Ragan 2001; Lawrence and Ochman2002). The first two show that genomes cancontain high proportions of “foreign” genes,up to 20%, acquired recently. The third ap-proach, in contrast, has limited power to detectvery recent transfers, but phylogenetic in-congruities are clearly evident when studyingthe genomes of distant species (Daubin et al.2003b). This apparent contradiction betweenthe different approaches can, in fact, be inter-preted as a fundamental underlying differencein the time scale considered. An individual ge-nome sequence corresponds to the shortesttime scale. It is a snapshot of the genetic infor-mation of a species (or strain) at a particularinstance in time. Such a genomic snapshot cancontain hundreds of recently acquired genes,the overwhelming majority of which are des-tined to disappear in the short term, leavinglittle trace in gene phylogenies (Daubin et al.2003b; Lerat et al. 2005). Analysis of recentlyacquired genes shows that the vast majorityare orphans, or “ORFans” (i.e., genes that haveno homologs in the other known genomes)(Siew and Fischer 2003). One possible explana-tion is that these genes originate from bacterio-phages that have integrated into the genome. Tobe retained in the longer term, they would haveto turn out to be useful for their host (Daubinet al. 2003a; Daubin and Ochman 2004a,b; Cor-tez et al. 2009; Bobay et al. 2014).

Horizontal Transfer and Adaptation

The adaptive role of horizontal transfer in bac-teria is well established. In particular, there arelong stretches of genomes called “islands” that

are only present sporadically in a given species,and are associated with pathogenicity, symbio-sis with another organism (e.g., a plant), orother ecological characteristics (Dobrindt et al.2004). The grouping of these genes in islandsis probably a result of the fact that these genesare associated with mobile elements (transpo-sons, bacteriophages) that tend to recombinewith each other and thus are inserted in closeproximity to each other, which then promotestheir simultaneous transfer from one genometo another. Interestingly, these islands usuallycontain numerous “ORFans” whose function,if they have one, has not yet been discovered(Siew and Fischer 2003).

These examples are evidence for the exis-tence of recent horizontal transfer in conjunc-tion with immediate environmental benefits,but there are also many indications suggestingthat ancient transfers have been able to toucheven the most fundamental cellular function.One example is the case of reverse gyrase, a pro-tein that changes the conformation of the chro-mosome, is found in all hyperthermophilic andsome thermophilic organisms (Bacteria andArchaea) and is thought to have been acquiredrepeatedly to adapt to this unique environment(Brochier-Armanet and Forterre 2006). Also,many examples of transfers of genes encodingtRNA synthetases, whose function is to load theamino acids onto their tRNAs before transla-tion, have been described between phylogenet-ically distant organisms (Fournier et al. 2015).The selection pressures that promote suchtransfers are still poorly understood, but it ispossible that these enzymes, which generallyoperate without interacting with other proteins,and whose substrates (an amino acid andtRNA) are highly conserved in evolution andcan hence adapt relatively easily to a new cellularenvironment. This type of reasoning is consis-tent with the “hypothesis of complexity” (Jainet al. 1999), which maintains that the number ofmolecular interactions of the protein encodedby a gene is a barrier to transfer. For example,genes involved in complex molecular structures,such as ribosomes or DNA replication machin-ery, are considered less likely to be replaced byremote homologs, because they have a low





probability of having preserved their numeroussites of interactions intact. However, there areexceptions to this rule, and, specifically, certainribosomal genes show clear traces of horizontaltransfer (Brochier et al. 2000).

EVOLUTION OF GENE REPERTOIRE

The Genomic Diversity of Life

Our appreciation of the magnitude of extantdiversity has broached new frontiers with theadvent of comparative genomics and the recog-nition of the differences in gene repertoires be-tween genomes. These differences are surpris-ing at all evolutionary scales, from the oldest tomost recent. As we have seen above, the ge-nomes of different strains of the same bacterialspecies can differ by several hundred genes. Theimportance of this phenomenon is such in bac-teria that it has led to the creation of the conceptof the “pan-genome,” the union of genes repre-sented in all individuals of the species. InE. coli, the pan-genome comprises .20,000 genes(and continues to gradually expand as new ge-nomes are sequenced), whereas the “core ge-nome,” the set of genes shared by all strains,comprises ,2000 genes (Touchon et al. 2009).At the other extreme, although all cellular or-ganisms have a DNA genome that they replicate,transcribe into messenger RNA, and translateusing a quasi-universal genetic code, only about60 genes have been found to be common to allliving genomes (Koonin 2003; Charlebois andDoolittle 2004), a number that is clearly insuf-ficient to perform all, or even any one, of theseuniversal functions. Several phenomena havebeen proposed to account for the marked dif-ferences in the gene repertoire:

† Gene duplication;

† Gene loss;

† Horizontal transfer of genes from cellularorganisms or viruses;

† Saturation of the signal of homology. Afterdiverging for a very long time or with veryhigh rates of evolution, genes can accumu-late so many substitutions that they will nolonger be recognizable as homolog;

† The origin of new genes from nonfunctionalsequences, or combinations of pieces of pre-existing genes.

The relative contribution of the differentphenomena has been difficult to assess, andeach probably accounts for disparities at differ-ent evolutionary scales. Differences in gene rep-ertoires between strains of the same species aremost probably explained by recent horizontaltransfer. Although the diversity of genes presentin the pan-genome of certain bacterial andarchaeal species contains a reservoir of genesallowing to adapt to a variety of conditions(Szollosi et al. 2006, cf. above; Touchon et al.2009), it seems more plausible to see these var-iations of gene content essentially as the result ofa highly dynamic process in which DNA inte-gration from selfish elements is quickly coun-terbalanced by deletion of even slightly harm-ful DNA (Daubin et al. 2003a; Collins et al.2011; Szollosi and Daubin 2012). In a way, thepan-genome observed in bacteria could be anequivalent to the junk DNA found in many eu-karyotic genomes, with the difference that eu-karyotic species with small population sizes areusually inapt to eliminate this DNA (Lynch andConery 2003). In Bacteria and Archaea, somelineages show strong tendencies to reduction oftheir genome, a feature that is generally relatedto lifestyle such as obligatory parasitism or en-dosymbiosis (Ochman and Moran 2001). It hasbeen proposed that there is a deletion bias in allbacterial genomes, normally offset by horizon-tal transfer, and that endosymbionts and otherparasites living in very confined spaces have lostthis source of new genes (Mira et al. 2001). Onthe other hand, if the gene duplications seemto occur spontaneously in bacterial genomes,multigene families are relatively rare in theseorganisms, compared with eukaryotes, and asubstantial portion of the genes of these multi-gene families could have expanded by horizon-tal gene transfer rather than duplication (Leratet al. 2005; Treangen and Rocha 2011). At deep-er evolutionary time scales, the differencesbetween gene content among domains of lifecould be explained by the saturation of the sig-nal of homology. Basic approaches searching for





nearly universal genes usually identify only a fewgenes (,60) that can be safely traced to the lastuniversal cellular ancestor (LUCA). This is ob-viously not sufficient to accomplish any of thefunctions that are believed to have been presentin this organism (e.g., functions that are univer-sal to cellular organisms), such as DNA replica-tion, transcription, translation, or membranesynthesis. It is of course possible that some ofthese functions were acquired after LUCA inde-pendently by its descendants (Koonin and Mar-tin 2005; Forterre 2013), but the loss of the sig-nal for recognizing homologs is very likely toplay a significant role in the failure to assigngenes to ancestral genomes (Daubin and Och-man 2004a; Elhaik et al. 2006).

HORIZONTAL GENE TRANSFER AND THETREE OF LIFE

After a century of stasis, distinguished onlyby the promotion of “Monera” and Fungi fromthe rank of phyla to kingdoms (Haeckel 1866;Whittaker 1969), the tree of life underwent rad-ical reorganization with the rise of molecularphylogeny. It was in the 1970s, with the workof Fox and Woese (Fox et al. 1977; Woese andFox 1977; Woese et al. 1990) on the RNA of thesmall subunit of the ribosome (termed 16S inprokaryotes and 18S in eukaryotes), that molec-ular phylogeny was systematically implementedto establish a phylogenetic classification of theprokaryotic world, and more generally a tree oflife. Since then, the diversity of life has been seenas comprised of three major domains, Archaea,Bacteria, and Eukarya. Most of the diversity rec-ognized before Woese (e.g., by Haeckel or Whit-tacker) belonged to the last domain, Eukarya,but because we have the tools to perceive ge-nome diversity, the first two domains havecome to be appreciated to be at least as diverse.

However, as popular as the tree of life basedon 16/18S RNA has been, it quickly proved tobe limited in its ability to resolve importantparts of the history of life as other gene markerscontradicted many of the relationships it sug-gested. Most notably, other phylogenetic mark-ers supported different relationships in the earlybranches of the tree, especially among bacterial

(or archaeal) phyla and between Archaea andEukarya (Brown and Doolittle 1997). With thedevelopment of genome sequencing, the com-bination of genetic markers to resolve deeprelationships in the tree of life became popu-lar (Delsuc et al. 2005), but again led onlyto ephemeral conclusions: different so-called“phylogenomic” studies identified very differ-ent numbers of phylogenetic markers potential-ly informative to infer the tree of life (with var-iations among studies from 14 to .50 genes),each combination of these markers pleading fordifferent trees, and different phylogenetic meth-ods yielded conflicting signals (see review inGribaldo et al. 2010). Metagenomic studies arenow bringing new incentive to these approachesby providing genomic sequences for previouslyunknown organisms, which turn out to be keyto resolve, for instance, the relationships be-tween Eukarya and Archaea (Spang et al.2015). These new results indicate that Eukaryaare in fact nested within the archaeal domainrather than being its sister group, a relationshipthat was proposed earlier based on individualmarkers (Rivera and Lake 1992; Tourasse andGouy 1999). However, none of these approachesaccount for the fact that individual genes havecomplex and, most certainly, different histories,but rather simply combine phylogenetic mark-ers, constraining them to a shared story, and as aresult are bound to produce indecisive represen-tations of the history of life. Reconstructingthe history of life based on molecular data willrequire the development of more principledmethodologies that explicitly deal with the com-plex processes of gene evolution (Boussau andDaubin 2010; Szollosi et al. 2015).

Gene Tree/Species Tree Models Are Key toReconstructing the History of Life

Although phylogeny seeks to reconstruct therelationships among species (etymologically,the genesis of species), molecular phylogeneticshas long focused on a different objective. Forcontingent and practical reasons, molecularphylogenetic analysis has mainly developed inthe context of the analysis of the histories of“genes.” The evolution of biological sequences





is subject to many factors and complex process-es, but one of these processes has been thesubject of most studies: the replacement of aletter of the nucleotide (or protein) alphabet byanother. Models attempting to describe thesesubstitutions are numerous, and are becom-ing more and more complex, gradually relax-ing simplifying assumptions made by previousmodels (Felsenstein 2004). We now know thatthe probability of replacement of a nucleotideor amino acid by another varies according toits biochemical properties; that all sites of amolecule are not subject to the same constraintsand that their evolutionary rate varies accord-ingly; that these constraints also vary over timeand that changes within a molecule can facili-tate or prevent others; and that the conditionsin which an organism lives can also affect theseprocesses. Increasingly sophisticated attemptshave been made to incorporate these into mod-els of sequence evolution, but much remainsto be accounted for (Boussau and Gouy 2006;Dutheil and Boussau 2008; Lartillot et al. 2009;Lartillot and Poujol 2010; Matsumoto et al.2015).

As sophisticated as these models become,they cannot solve the problem of phylogeny inits primary sense. For the history of the speciesis not a simple transposition of the history of agene or a genomic sequence (Maddison 1997).As we have seen before, the history of a gene ismarked by a series of speciation, duplication,losses, and horizontal transfer (Fig. 1). In addi-tion, genes evolve in populations, and differentallelic forms of a gene can coexist for periodsthat may span several speciation events. All ofthese events prevent us from interpreting thephylogeny of a gene directly as a phylogeny ofspecies. Hence, to reconstruct the history of spe-cies based on molecular data it is necessary, inaddition to modeling sequence evolution, to beable to model the relationships between a genetree and a species tree. This is currently an activeavenue of research, although a complete modelaccounting for all mechanisms is still lacking(Szollosi et al. 2015). Most relevant to the infer-ence of the tree of life, probabilistic modelscombining the likelihood of gene duplication,transfer, and loss scenarios and sequence evolu-

tion have been recently developed (Szollosi et al.2013a; Sjostrand et al. 2014). The previouslymentioned application to cyanobacteria hasshown that these models allow the reconstruc-tion of a species tree based on the full set ofgenes present in genomes, and not only thosewidely represented among species (Szollosiet al. 2012, 2013a,b). Importantly, under a mod-el accounting for lateral gene transfer, the re-constructed species tree contains informationon the relative timing of speciation of differentgroups, because gene transfer can only occurbetween species that have been contemporaries(Fig. 2) (Szollosi et al. 2012). This informationis completely independent from any other in-formation about the timing of events, such asfossils or molecular clocks, and can therefore beused to complete these data. It has been shownthat, using the complete set of gene trees thatcan be reconstructed from a set of genomes, onecan reconstruct a fully resolved species tree, withevents of speciation ordered in time (Szollosi etal. 2012). This approach has been applied onlyto parts of the tree of life because it is compu-tationally intensive and cannot yet be applied tohundreds or thousands of species. However, itsadvantages are many because it also provides anexplicit reconstruction of the events of dupli-cation, loss, and transfer along the phylogeny,and hence also reconstruct ancestral genomes ateach node of the species tree. Future develop-ments will hopefully allow the generalization ofsuch methods to larger data sets and an appli-cation to a well-sampled tree of life.

CONCLUDING REMARKS

Lateral gene transfer is a powerful evolutionaryforce, allowing the combination of molecularfunctions well beyond the species boundaries.However, its success as a process has long beenseen by evolutionary biologists as a barrier toreconstructing the patterns of evolution (i.e.,the tree of life). This difficulty is not so muchconceptual as methodological and recent de-velopments allow to use lateral gene transferas information for reconstructing the historyof life. Under this view, gene transfer even un-veils unforeseen opportunities to address long-





standing questions such as the reconstructionof the timing of life evolution or the rootof the tree of life. The recent realization thathorizontal gene transfer has been extensivethroughout the evolution of the eukaryoticdomain (Keeling and Palmer 2008; Andersson2009) will allow to compare the informationderived from genome histories to the fossilrecord.

ACKNOWLEDGMENTS

We thank Sophie Abby for allowing us to useher drawings in Figure 2. V.D. is supported by

the French Agence Nationale de la Recherche(ANR) through Grant (ANR-10-BINF-01-01)“Ancestrome.” G.J.S. is supported by Marie Cu-rie Grant CIG 618438 “Genestory.”

REFERENCES

Abby SS, Tannier E, Gouy M, Daubin V. 2010. Detectinglateral gene transfers by statistical reconciliation of phy-logenetic forests. BMC Bioinformatics 11: 324.

Abby SS, Tannier E, Gouy M, Daubin V. 2012. Lateral genetransfer as a support for the tree of life. Proc Natl Acad Sci109: 4962–4967.

Andersson JO. 2009. Horizontal gene transfer between mi-crobial eukaryotes. Methods Mol Biol 532: 473–487.

Species tree

Gene tree

Gene tree/species tree reconciliation

T

?

L

D

t2

t2

t1

t1

Figure 2. Gene tree/species tree reconciliation and the timing of events. Models of reconciliation invokinghorizontal gene transfer (T, in addition to duplications, D, and losses, L) implicitly or explicitly imply a partialorder of evolutionary events in a tree. Here, the scenario of reconciliation of the gene tree and the species containsa transfer that implies that the speciation at time t1 occurred before the speciation at t2. The reconciliation of alarge number of gene trees (typically, from all the homologous genes represented in the genomes under study)with a species tree can yield a fully resolved time order of evolutionary events (Szollosi et al. 2012).





Avery OT, Macleod CM, McCarty M. 1944. Studies on thechemical nature of the substance inducing transforma-tion of pneumococcal types: Induction of transformationby a desoxyribonucleic acid fraction isolated from Pneu-mococcus Type III. J Exp Med 79: 137–158.

Bansal MS, Alm EJ, Kellis M. 2012. Efficient algorithms forthe reconciliation problem with gene duplication, hori-zontal transfer and loss. Bioinformatics 28: 283–i291.

Beiko RG, Harlow TJ, Ragan MA. 2005. Highways of genesharing in prokaryotes. Proc Natl Acad Sci 102: 14332–14337.

Bobay L-M, Touchon M, Rocha EPC. 2014. Pervasive do-mestication of defective prophages by bacteria. Proc NatlAcad Sci 111: 12127–12132.

Boussau B, Daubin V. 2010. Genomes as documents ofevolutionary history. Trends Ecol Evol 25: 224–232.

Boussau B, Gouy M. 2006. Efficient likelihood computa-tions with nonreversible models of evolution. Syst Biol55: 756–768.

Brochier-Armanet C, Forterre P. 2006. Widespread distribu-tion of archaeal reverse gyrase in thermophilic bacteriasuggests a complex history of vertical inheritance andlateral gene transfers. Archaea 2: 83–93.

Brochier C, Philippe H, Moreira D. 2000. The evolutionaryhistory of ribosomal protein RpS14: Horizontal genetransfer at the heart of the ribosome. Trends Genet 16:529–533.

Brown JR, Doolittle WF. 1997. Archaea and the prokaryote-to-eukaryote transition. Microbiol Mol Biol Rev 61: 456–502.

Canchaya C, Fournous G, Brussow H. 2004. The impact ofprophages on bacterial chromosomes. Mol Microbiol53: 9–18.

Charlebois RL, Doolittle WF. 2004. Computing prokaryoticgene ubiquity: Rescuing the core from extinction. Ge-nome Res 14: 2469–2477.

Collins RE, Merz H, Higgs PG. 2011. Origin and evolutionof gene families in bacteria and archaea. BMC Bioinfor-matics 12: S14.

Cortez D, Forterre P, Gribaldo S. 2009. A hidden reservoir ofintegrative elements is the major source of recently ac-quired foreign genes and ORFans in archaeal and bacte-rial genomes. Genome Biol 10: R65.

Daubin V, Ochman H. 2004a. Bacterial genomes as new genehomes: The genealogy of ORFans in E. coli. Genome Res14: 1036–1042.

Daubin V, Ochman H. 2004b. Start-up entities in the originof new genes. Curr Opin Genet Dev 14: 616–619.

Daubin V, Perriere G. 2003. GþC3 structuring along thegenome: A common feature in prokaryotes. Mol BiolEvol 20: 471–483.

Daubin V, Lerat E, Perriere G. 2003a. The source of laterallytransferred genes in bacterial genomes. Genome Biol 4:R57.

Daubin V, Moran NA, Ochman H. 2003b. Phylogeneticsand the cohesion of bacterial genomes. Science 301:829–832.

Delsuc F, Brinkmann H, Philippe H. 2005. Phylogenomicsand the reconstruction of the tree of life. Nat Rev Genet6: 361–375.

Dobrindt U, Hochhut B, Hentschel U, Hacker J. 2004. Ge-nomic islands in pathogenic and environmental micro-organisms. Nat Rev Microbiol 2: 414–424.

Dutheil J, Boussau B. 2008. Non-homogeneous models ofsequence evolution in the Bioþþ suite of libraries andprograms. BMC Evol Biol 8: 255.

Elhaik E, Sabath N, Graur D. 2006. The “inverse relationshipbetween evolutionary rate and age of mammalian genes”is an artifact of increased genetic distance with rate ofevolution and time of divergence. Mol Biol Evol 23: 1–3.

Felsenstein J. 2004. Inferring Phylogenies. Sinauer Associates,Sunderland, MA.

Forterre P. 2013. Why are there so many diverse replicationmachineries? J Mol Biol 425: 4714–4726.

Fournier GP, Andam CP, Gogarten JP. 2015. Ancient hori-zontal gene transfer and the last common ancestors. BMCEvol Biol 15: 70.

Fox GE, Magrum LJ, Balch WE, Wolfe RS, Woese CR. 1977.Classification of methanogenic bacteria by 16S ribosomalRNA characterization. Proc Natl Acad Sci 74: 4537–4541.

Gribaldo S, Poole AM, Daubin V, Forterre P, Brochier-Ar-manet C. 2010. The origin of eukaryotes and their rela-tionship with the Archaea: Are we at a phylogenomicimpasse? Nat Rev Microbiol 8: 743–752.

Griffith F. 1928. The significance of pneumococcal types. JHyg (Lond) 27: 113–159.

Guindon S, Perriere G. 2001. Intragenomic base contentvariation is a potential source of biases when search-ing for horizontally transferred genes. Mol Biol Evol 18:1838–1840.

Haeckel EH. 1866. Generelle morphologie der organismen.Georg Reimer, Berlin.

Jain R, Rivera MC, Lake JA. 1999. Horizontal gene transferamong genomes: The complexity hypothesis. Proc NatlAcad Sci 96: 3801–3806.

Keeling PJ, Palmer JD. 2008. Horizontal gene transfer ineukaryotic evolution. Nat Rev Genet 9: 605–618.

Koonin EV. 2003. Comparative genomics, minimal gene-sets and the last universal common ancestor. Nat RevMicrobiol 1: 127–136.

Koonin EV, Martin W. 2005. On the origin of genomes andcells within inorganic compartments. Trends Genet 21:647–654.

Lang AS, Beatty JT. 2007. Importance of widespread genetransfer agent genes in a-proteobacteria. Trends Micro-biol 15: 54–62.

Lartillot N, Poujol R. 2010. A phylogenetic model for inves-tigating correlated evolution of substitution rates andcontinuous phenotypic characters. Mol Biol Evol 28:729–744.

Lartillot N, Lepage T, Blanquart S. 2009. PhyloBayes 3: ABayesian software package for phylogenetic reconstruc-tion and molecular dating. Bioinformatics 25: 2286–2288.

Lassalle F, Perian S, Bataillon T, Nesme X, Duret L, Daubin V.2015. GC-content evolution in bacterial genomes: Thebiased gene conversion hypothesis expands. PLoS Genet11: e1004941.

Lawrence JG, Ochman H. 1998. Molecular archaeologyof the Escherichia coli genome. Proc Natl Acad Sci 95:9413–9417.





Lawrence JG, Ochman H. 2002. Reconciling the many facesof lateral gene transfer. Trends Microbiol 10: 1–4.

Lawrence JG, Roth JR. 1996. Selfish operons: Horizontaltransfer may drive the evolution of gene clusters. Genetics143: 1843–1860.

Lerat E, Daubin V, Ochman H, Moran NA. 2005. Evolution-ary origins of genomic repertoires in bacteria. PLoS Biol3: e130.

Lynch M, Conery JS. 2003. The origins of genome complex-ity. Science 302: 1401–1404.

Maddison WP. 1997. Gene trees in species trees. Syst Biol46: 523–536.

Matsumoto T, Akashi H, Yang Z. 2015. Evaluation of an-cestral sequence reconstruction methods to infer nonsta-tionary patterns of nucleotide substitution. Genetics 200:873–890.

Mell JC, Redfield RJ. 2014. Natural competence and theevolution of DNA uptake specificity. J Bacteriol 196:1471–1483.

Mira A, Ochman H, Moran NA. 2001. Deletional bias andthe evolution of bacterial genomes. Trends Genet 17:589–596.

Ochman H, Moran NA. 2001. Genes lost and genes found:Evolution of bacterial pathogenesis and symbiosis. Sci-ence 292: 1096–1099.

Ochman H, Lawrence JG, Groisman EA. 2000. Lateral genetransfer and the nature of bacterial innovation. Nature405: 299–304.

Ochman H, Lerat E, Daubin V. 2005. Examining bacterialspecies under the specter of gene transfer and exchange.Proc Natl Acad Sci 102: 6595–6599.

Price MN, Arkin AP, Alm EJ. 2006. The life-cycle of operons.PLoS Genet 2: e96.

Puigbo P, Wolf YI, Koonin EV. 2010. The tree and net com-ponents of prokaryote evolution. Genome Biol Evol 2:745–756.

Ragan MA. 2001. On surrogate methods for detecting lateralgene transfer. FEMS Microbiol Lett 201: 187–191.

Redfield RJ, Schrag MR, Dean AM. 1997. The evolution ofbacterial transformation: Sex with poor relations. Genet-ics 146: 27–38.

Rivera MC, Lake JA. 1992. Evidence that eukaryotes andeocyte prokaryotes are immediate relatives. Science 257:74–76.

Siew N, Fischer D. 2003. Twenty thousand ORFan microbialprotein families for the biologist? Structure 11: 7–9.

Sjostrand J, Tofigh A, Daubin V, Arvestad L, Sennblad B,Lagergren J. 2014. A Bayesian method for analyzing lat-eral gene transfer. Syst Biol 63: 409–420.

Spang A, Saw JH, Jørgensen SL, Zaremba-NiedzwiedzkaK, Martijn J, Lind AE, van Eijk R, Schleper C, Guy L,Ettema TJG. 2015. Complex archaea that bridge the gapbetween prokaryotes and eukaryotes. Nature 521: 173–179.

Sueoka N. 1962. On the genetic basis of variation and het-erogeneity of DNA base composition. Proc Natl Acad Sci48: 582–592.

Szollosi GJ, Daubin V. 2012. Modeling gene family evolutionand reconciling phylogenetic discord. Methods Mol Biol856: 29–51.

Szollosi GJ, Derenyi I, Vellai T. 2006. The maintenance of sexin bacteria is ensured by its potential to reload genes.Genetics 174: 2173–2180.

Szollosi GJ, Boussau B, Abby SS, Tannier E, Daubin V. 2012.Phylogenetic modeling of lateral gene transfer recon-structs the pattern and relative timing of speciations.Proc Natl Acad Sci 109: 17513–17518.

Szollosi GJ, Rosikiewicz W, Boussau B, Tannier E, Daubin V.2013a. Efficient exploration of the space of reconciledgene trees. Syst Biol 62: 601–912.

Szollosi GJ, Tannier E, Lartillot N, Daubin V. 2013b. Lateralgene transfer from the dead. Syst Biol 62: 386–397.

Szollosi GJ, Tannier E, Daubin V, Boussau B. 2015. Theinference of gene trees with species trees. Syst Biol 64:e42–e62.

Than C, Ruths D, Nakhleh L. 2008. PhyloNet: A softwarepackage for analyzing and reconstructing reticulateevolutionary relationships. BMC Bioinformatics 9: 322.

Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S,Bidet P, Bingen E, Bonacorsi S, Bouchier C, Bouvet O, etal. 2009. Organised genome dynamics in the Escherichiacoli species results in highly diverse adaptive paths. PLoSGenet 5: e1000344.

Tourasse NJ, Gouy M. 1999. Accounting for evolutionaryrate variation among sequence sites consistently changesuniversal phylogenies deduced from rRNA and protein-coding genes. Mol Phylogenet Evol 13: 159–168.

Treangen TJ, Rocha EPC. 2011. Horizontal transfer, notduplication, drives the expansion of protein families inprokaryotes. PLoS Genet 7: e1001284.

Whittaker RH. 1969. New concepts of kingdoms of organ-isms. Science 163: 150–160.

Woese CR, Fox GE. 1977. Phylogenetic structure of the pro-karyotic domain: The primary kingdoms. Proc Natl AcadSci 74: 5088–5090.

Woese CR, Kandler O, Wheelis ML. 1990. Towards a nat-ural system of organisms: Proposal for the domainsArchaea, Bacteria, and Eucarya. Proc Natl Acad Sci 87:4576–4579.





January 22, 20162016; doi: 10.1101/cshperspect.a018036 originally published onlineCold Spring Harb Perspect Biol

Vincent Daubin and Gergely J. Szöllosi Horizontal Gene Transfer and the History of Life

Subject Collection Microbial Evolution

Genetics, and RecombinationNot So Simple After All: Bacteria, Their Population

William P. HanageAgeGenome-Based Microbial Taxonomy Coming of

Donovan H. ParksPhilip Hugenholtz, Adam Skarshewski and

Realizing Microbial EvolutionHoward Ochman

Horizontal Gene Transfer and the History of LifeVincent Daubin and Gergely J. Szöllosi

EvolutionThe Importance of Microbial Experimental Thoughts Toward a Theory of Natural Selection:

Daniel Dykhuizen

Early Microbial Evolution: The Age of AnaerobesWilliam F. Martin and Filipa L. Sousa

Prokaryotic GenomesCoevolution of the Organization and Structure of

Marie Touchon and Eduardo P.C. Rocha

Microbial SpeciationB. Jesse Shapiro and Martin F. Polz

Mutation and Its Role in the Evolution of BacteriaThe Engine of Evolution: Studying−−Mutation

Ruth HershbergCampylobacter coli

and Campylobacter jejuniThe Evolution of

Samuel K. Sheppard and Martin C.J. Maiden

Mutation)Natural Selection Mimics Mutagenesis (Adaptive The Origin of Mutants Under Selection: How

Sophie Maisnier-Patin and John R. Roth

EvolutionPaleobiological Perspectives on Early Microbial

Andrew H. Knoll

Preexisting GenesEvolution of New Functions De Novo and from

Joakim NäsvallDan I. Andersson, Jon Jerlström-Hultqvist and

http://cshperspectives.cshlp.org/cgi/collection/ For additional articles in this collection, see

Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved


http://cshperspectives.cshlp.org/cgi/collection/

http://cshperspectives.cshlp.org/cgi/collection/

http://cshperspectives.cshlp.org/cgi/adclick/?ad=55917&adclick=true&url=http%3A%2F%2Fwww.genelink.com


horizontal gene transfer and the history of life

Documents