horizontal gene transfer || endosymbiotic gene transfer

C H A P T E R 27

Endosymbiotic Gene Transfer: A SpecialCase of Horizontal Gene Transfer Germaneto Endosymbiosis, the Origins of Organellesand the Origins of EukaryotesKatrin Henze, Claus Schnarrenberger and William Martin

Endosymbiotic gene transfer describes the pro-cess through which chloroplasts and mitochon-dria relinquished the majority of their genes tothe nucleus while not having surrendered themajority of proteins integral to the eubacterialnature of their metabolism. It is a special case oflateral gene transfer that was very importantfor the establishment of biochemical compart-mentation during the evolution of eukaryoticcells. Many examples of endosymbiotic genetransfer in the history of higher plant genes forchloroplast-cytosolic isoenzymes of the Calvincycle and glycolysis have been considered inthe past few years. The data indicate that nu-clear genes for almost all glycolytic enzymesof the eukaryotic cytosol were acquired fromeubacteria early in eukaryotic evolution, prob-ably in the course of the endosymbiotic eventthat gave rise to the origin of mitochondria. Thegenes for enzymes that are possessed both bythe symbiont and host during a given endo-symbiosis are redundant. In such cases, it is ob-served that the intruding gene contributed bythe symbiont had a very high likelihood of suc-cessful gene transfer. But the protein productsof genes that were transferred from symbiont tohost chromosomes have been surprisingly oftenrerouted to compartments other than that from

which the genes were donated. Because ofthis, the localization of a protein within the eu-karyotic cell is not per se an indicator of the evo-lutionary origin of its gene. The evolutionaryhistory of the enzymes of central carbon metab-olism in eukaryotes and the role of lateral genetransfer in that process is summarized. These re-sults are considered in light of the ability ofcompeting alternative theories for the origins ofeukaryotes to account for the observations.

INTRODUCTION

Genes encoded in organellar genomes attestbeyond all reasonable doubt to the eubacterialancestry of chloroplasts (Martin et al., 1998) andmitochondria (Gray et al., 1999). But how doesendosymbiotic theory account for the originof organellar proteins that are not encoded inorganellar DNA? Their fate is commonly ex-plained with the help of a scenario elegantlyargued by Weeden (1981) that is known as the“product specificity corollary” (also known asthe “gene transfer corollary”) to endosymbiotictheory. It posits that during the course ofeukaryotic history, the majority of genes forproteins integral to organellar metabolism were

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transferred to the nucleus where they becameintegrated into the regulatory hierarchy of thenucleus and acquired a transit peptide, so thatthe functional gene products could be reim-ported into the organelle of their genetic originon a daily basis since. This is a reasonable andlogical scenario that satisfyingly explains whyorganelles have retained so much of their bio-chemically eubacterial heritage while havingrelinquished to the nucleus the majority ofgenes necessary to have done so. Though ulti-mately incorrect in the majority of specific casesin which it has been tested (Martin andSchnarrenberger, 1997; Martin, 1998), primarilydue to the unfulfilled predictions that it gener-ates about the origin of cytosolic enzymes, thegene transfer corollary does manage adequatelyto account for several organelle-to-nucleus genetransfer events (Martin and Cerff, 1986; Baldaufand Palmer, 1990; Brennicke et al., 1993; Martinet al., 1993).

However, the simple phrase “organelle-to-nucleus gene transfer” raises a different, muchmore difficult and in our view much morepressing question, namely: what is the origin ofthe nuclear genome under endosymbiotictheory? When Weeden (1981) formulated thegene transfer corollary, it was not knownwhether chloroplasts and mitochondria weredescendants of endosymbionts or not, and hisconsiderations generated testable predictionsthat could help to muster evidence in favor (orin disfavor) of that view (Gray and Doolittle,1982). A salient element of that reasoningwas that nuclear-encoded organellar enzymesshould reflect the evolutionary history of thesymbiont while cytosolic enzymes in eukary-otes should reflect the evolutionary history ofthe host (Weeden, 1981; Gray and Doolittle,1982). Although we now know with certaintythat plastids and mitochondria are descendantsof free-living eubacteria, and although we arereasonably (but not completely) confident thatthe origin of mitochondria preceeded the originof chloroplasts in evolution, it is perhaps sur-prising that endosymbiotic theory is just asmuch in the dark about the origin of the hostthat acquired mitochondria today as it was20 years ago. In other words, in order to have anull hypothesis for the patterns of similarity to

be expected for a given eukaryotic nuclear gene,one has to have a biological model for theorigins of eukaryotes that generates suchpredictions.

What was the host? Biologists have a numberof different suggestions, but no generally ac-cepted answer to that question, but there are afew important clues that can serve as a guide-line. Discovery of the archaebacterial nature ofcomponents of the nuclear genetic apparatus(Pühler et al., 1989; Ouzounis and Sander, 1992;Rowlands et al., 1994; Langer et al., 1995) andthe results of extensive molecular phylogeneticwork have slowly unveiled the host that ac-quired the mitochondrion as a descendant (inpart or in whole) of an archaebacterium (Zillig etal., 1989; Ouzounis and Sander, 1992; Brownand Doolittle, 1995, 1997; Langer et al., 1995;Doolittle, 1996; Ribiero and Golding, 1998;Rivera et al., 1998). Under the simplest set ofpremises possible, this means that the hostcell that acquired the mitochondrion was anarchaebacterium (Doolittle, 1996; Martin andMüller, 1998). However, many other more com-plicated models involving more than two sym-biotic partners to give rise to a mitochondrion-bearing eukaryote have been elaborated. It isworthwhile briefly to recapitulate a few of thesemodels to see what sorts of predictions theygenerate, in particular about the evolution ofmolecules that occur in the cytosol of contempo-rary eukaryotes.

Probably the most popular model up until afew years ago is what is best described as theachezoa model (Cavalier-Smith 1987a,b), alsosometimes called the “classical hypothesis”(Doolittle, 1980, 1998). Under this view, a primi-tively amitochondriate, nucleus-bearing cell (anarchezoon) is suggested to have arisen from anarchaebacterial ancestor in a process that in-volved the origin of typical eukaryotic features(cytoskeleton, endocytosis, nucleus and mi-tosis). A member of that ancient group acquiredthe mitochondrion through endosymbiosis,while others (the suspectedly most primitiveeukaryotes) remained amitochondriate up tothe present day. This model has not withstoodthe scrutiny of molecular phylogeneticists, whohave found that all amitochondriate eukaryotesstudied to date possessed a mitochondrion in

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their evolutionary past, but lost the organellesubsequently (Clark and Roger, 1995; Germot etal., 1997; Embley and Hirt, 1998; Martin andMüller, 1998; Gray et al., 1999; Roger, 1999;Tovar et al., 1999; Müller, 2000; Philippe et al.,2000), the evidence for which is founded in nu-clear genes in these amitochondriate organismswhich reflect a mitochondrial ancestry (that is,they were transferred from the organelle to thenucleus via endosymbiotic gene transfer). Fur-thermore, the achezoa model clearly predicts alleukaryotes in general, and amitochondriateeukaryotes in particular, to possess archae-bacterial enzymes of cytosolic metabolism,because under this model, amitochondriateprotists are, on the bottom line, to be inter-preted as direct descendants of archaebacteria(Cavalier-Smith, 1987b). A version of theachezoa model has been published under thename of the “ox-tox” hypothesis (Anderssonand Kurland, 1999), but it is not fundamentallydifferent from the achezoa model, rather it isvery similar to 1975 formulations of the endo-symbiont hypothesis (John and Whatley, 1975).For a further discussion of this matter, see Rotteet al. (2000) and Martin (2000).

A second model is that of Lynn Margulis,which entails a symbiosis between a spiro-chete and a Thermoplasma-like archaebacterium(Sagan, 1967; Margulis, 1970, 1996) to give rise toa primitive, flagellated, mitochondrion-lacking(amitochondriate) eukaryote that subsequentlyacquired the mitochondrion through endo-symbiosis. In the most recent formulation, thatmodel suggests that the spirochete endosym-biont also gave rise to the nuclear compart-ment (Margulis et al., 2000). This model predictsthat eukaryotic enzymes should, in general, bemore similar to Thermoplasma enzymes than tohomologues from other prokaryotes, but thesequence of the Thermoplasma genome did notbear out that prediction (Cowan, 2000).

A third model that has been discussed atlength in the literature is the idea that the nu-cleus was an endosymbiont. This model isexactly as old as the notion that chloroplastsdescend from cyanobacteria, because the firstpaper thoroughly to argue the latter case(almost 100 years ago) also argued the former,albeit more briefly (Mereschkowsky, 1905). The

idea that the nuclear compartment is theremnant of an ancient endosymbiosis sufferedextinction for many decades (Mereschkowsky,1905), but it was resuscitated in 1994 (Lake andRivera, 1994), was rejuvenated in 1996 (Guptaand Golding, 1996), came more or less fully backto life in 1998 (Lopez-Garcia and Moreira, 1999)and has even been claimed to receive direct sup-port from data (Horiike et al., 2001). In these for-mulations, the nucleus is viewed as an archae-bacterial symbiont that took up residence in aeubacterial host. In Margulis’s formulation, aspirochete symbiont (that became the flagellumand the nucleus) took up residence in anarchaebacterial host. It should be noted thatthere are several severe cell biological problems(discussed in Martin, 1999b; Rotte and Martin,2001) with this model that are usually over-looked by its advocates, most notably (1) thatthe nucleus is not bounded by a double mem-brane, like chloroplasts and mitochondria, butrather by a folded single membrane, (2) thatthe nuclear membrane disintegrates at mitosis(viable chloroplasts and mitochondria neverlose their surrounding membranes), and (3) theway that the cytosol is separated from the nu-cleus has no similarity whatsoever to the waythat free-living prokaryotes are separatedfrom their environment. Perhaps most impor-tantly, “nucleosymbiotic” models derive anarchezoon (a nucleus-bearing but amito-chondriate eukaryote), whereby – as mentionedabove – available data indicate that all eu-karyotes, including those that lack mitochon-dria, once possessed mitochondria in theirevolutionary past, but lost them secondarily.Therefore, these models predict eukaryotes thatnever possessed mitochondria (achaezoa) to befound, descendants of the stem that acquiredmitochondria. Furthermore, with regard totheir statements about the cytosol, these modelswould ultimately predict eukaryotes to possessDNA both in the nucleus and in the cytosol (inaddition to genomes in chloroplasts andmitochondria).

The fourth, and arguably simplest, currentmodel to derive a mitochondrion-bearing eu-karyote is called the “hydrogen hypothesis”(Martin and Müller, 1998). It posits that the hostcell of the mitochondrial symbiosis was an

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archaebacterium, specifically an autotrophic andH2-dependent archaebacterium, with an energymetabolism possibly similar to that found inmodern methanogens. It accounts for thecommon ancestry of mitochondria and hydro-genosomes – the H2-producing organelles ofATP-synthesis in anaerobic eukaryotes (Müller,1988, 1993; Embley and Hirt, 1998). It posits thateukaryotes acquired their heterotrophic lifestyle,including the genes and enzymes necessary forthat lifestyle, from the mitochondrial symbiontvia endosymbiotic gene transfer from theheterotrophic symbiont’s (eubacterial) to theautotrophic host’s (archaebacterial) chromo-somes (Martin and Müller, 1998). Under thismodel, the origins of mitochondria/hydro-genosomes and the origins of eukaryotes areidentical and the nucleus is a subsequenteukaryotic invention, the origin of which prob-ably relates mechanistically to the origin ofeubacterial lipid synthesis in eukaryotes (Martin,1999b). This model explicitly predicts eukaryotesto have a eubacterial glycolytic pathway in thecytosol as the result of specifically selectedendosymbiotic gene transfer from symbiont tohost prior to the evolution of a mitochondrialprotein import machinery.

RESULTS AND DISCUSSION

Evolution of two further enzymes ofcentral sugar phosphate metabolism inhigher plants

In previous work, we have studied the evolutionof several enzymes involved in sugar phosphatemetabolism in the chloroplast and cytosol ofhigher plants (Henze et al., 1994; Martin andSchnarrenberger, 1997; Martin and Herrmann,1998) and of the cytosolic homologues in severalprotists (Henze et al., 1995, 1998, 2001; Wu et al.,2001). Two enzymes whose gene origins havebeen unclear are ribose-5-phosphate isomerase(RPI), that catalyzes the freely revers-ible isomerization of ribose-5-phosphate andribulose-5-phosphate, and phosphoglucomutase(PGluM), that catalyzes the freely reversibleinterconversion of glucose-1-phosphate and glu-cose-6-phosphate. Homologues for both genes

from a variety of sources were collected fromGenBank and subjected to phylogenetic analysis(Figure 27.1).

The tree for RPI, which is a relatively shortenzyme of about 220 amino acids, does not pro-vide very sharp resolution, but it does revealthat the enzymes from plants, animals, andfungi are clearly more similar to eubacterialhomologues than they are to archaebacterialhomologues (Figure 27.1A). In spinach, there isonly one isoenzyme of RPI known; cell fraction-ation has shown it to be located in the plastid(Schnarrenberger et al., 1995). The subcellularlocalization of the two Arabidopsis enzymes in-ferred from the genome sequence is currentlyunknown. The plant enzyme does not branchspecifically with the cyanobacterial homologue,nor does the enzyme from animals and fungibranch specifically with proteobacterial homo-logues, as one might expect if these enzymeswere donated to eukaryotes from the ances-tors of plastids and mitochondria, respectively.This can be due to a number of factors, in-cluding the simple phylogenetic resolutionproblems involved with a protein that is only220 amino acids long or, alternatively, to hori-zontal gene transfer between free-living eu-bacteria subsequent to the origins of organelles(see below). It is noteworthy that the plantenzyme does not branch with its homologuesfrom animals and yeast, suggesting that theeubacterial donor of the plant gene was a dif-ferent bacterium from that which donated thegene to the heterotrophic eukaryotes sampled.

The tree for PGluM (Figure 27.1B) reveals thatthe eukaryotic genes are derived from a singleacquisition from a eubacterial donor, and thatthe higher plant chloroplast-cytosol isoenzymesare related by a gene duplication in the plant lin-eage, as has been observed for the majority ofchloroplast-cytosol isoenzymes studied to date(Martin and Schnarrenberger, 1997), and in con-trast to the predictions from the product speci-ficity corollary (Weeden, 1981). Archaebacterialhomologues of PGluM were not identified, butfurther searching revealed that eubacterialPGluM is related to phosphomannomutase(PMM) which does have homologues inarchaebacterial genomes (Figure 27.1B). Theplant PMM genes surveyed are descendants of


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eubacterial PMM genes, but again, not specifi-cally related to the cyanobacterial homologue(see below). Notably, Figure 27.1B shows thatthe PGluM sequence from the amitochondriateprotist Entamoeba histolytica (Ortner et al., 1997)is also an acquisition from eubacteria. In this

respect it is important to recall that althoughEntamoeba histolytica does not have either mito-chondria or hydrogenosomes, it was recentlydiscovered to possess a small, double membrane-bounded organelle in the cytosol – termed themitosome – that is most easily interpreted as an


FIGURE 27.1 Protein phylogenies for (A) ribose-5-phosphate isomerase and (B) phosphoglucomutase. The RPItree was inferred using ProtML (Adachi and Hasegawa, 1996) with local rearrangements and the JTT-F matrixstarting from the neighbor-joining topology. The PGluM tree was inferred with the neighbor-joining method(Saitou and Nei, 1987) from the Dayhoff distance matrix using Phylip (Felsenstein, 1993). Bootstrap proportions>80 are indicated at branches.

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intermediate stage in the evolutionary processof mitochonrion and hydrogenosome reduction(Tovar et al., 1999).

The evolution of compartmentalizedsugar phosphate metabolism in higherplants

Figure 27.2 (see color plates) summarizes the ob-servations from a large number of individualgene phylogenies published over the past yearsconcerning the enzymes of compartmentalizedsugar phosphate metabolism in higher plants.Importantly, all of the enzymes represented inthe figure, with the exception of the large sub-unit of Rubisco, are encoded in the nucleus.Color coding indicates whether the nuclear en-coded enzyme is (1) more similar to cyano-bacterial homologues (green), (2) more similarto eubacterial (but not specifically cyano-bacterial) homologues (blue), or (3) more similarto archaebacterial homologues (red). For the en-zymes shaded in gray, no statement is currentlypossible. The results summarized in the figurehave been discussed in further detail elsewhere(Martin and Schnarrenberger, 1997; Henze etal., 1998; Martin and Herrmann, 1998; Nowitzkiet al., 1998; Wu et al., 2001) In general, what weobserve is the following.

In the chloroplast, many of the enzymes ofcarbohydrate metabolism are indeed encodedby nuclear genes that were acquired from thecyanobacterial antecedent of plastids, asthe product specificity corollary predicts. Ex-amples are glyceraldehyde-3-phosphate de-hydrogenase (GAPDH) (Martin et al., 1993),phosphoglycerate kinase (PGK) (Brinkmannand Martin, 1996; Martin and Schnarren-berger, 1997), transketolase (TKL) (Martin,1998) and glucose-6-phosphate isomerase(GPI) (Nowitzki et al., 1998). But there aremany exceptions to this rule. Notably, many ofthe enzymes localized in the plastid compart-ment are encoded by genes that were acquiredfrom eubacteria, but – on the basis of availabledata – not from cyanobacteria. Examples arefructose-1,6-bisphosphatase (FBP) (Martin etal., 1996), triosephosphate isomerase (TPI)(Henze et al., 1994; Schmidt et al., 1995; Keeling

and Doolittle, 1997), glucose-6-phosphatedehydrogenase (G6PDH) (Wendt et al.,1999) and 6-phosphogluconate dehydro-genase (6PGDH) (Krepinsky et al., 2001). Oneenzyme in the chloroplast, enolase (ENO)(Hannaert et al., 2000) is more similar toarchaebacterial homologues than to eu-bacterial homologues. In those cases where thechloroplast enzyme does not reflect a cyano-bacterial origin, the nuclear gene for theenzyme arose through duplication of a pre-existing nuclear gene in the higher plant lineage.But as mentioned above, in all cases exceptenolase those pre-existing nuclear genes werethemselves acquisitions from eubacteria.

In the cytosol, almost without exception, all ofthe enzymes of central carbon metabolism inhigher plants are acquisitions from eubacteria.The exception is again enolase, which reflects anarchaebacterial origin (Hannaert et al., 2000).Another is phosphoglycerate kinase, where acyanobacterial enzyme has taken up residencein the cytosol. Very importantly, if one were toprepare Figure 27.2 for yeast or humans, thecytosolic portion of the figure would be exactlythe same, except that PPi-dependent PFK wouldbe missing, both PGK and 6GPDH would beblue (instead of green), the oxidative pentosephosphate cycle would be in the cytosol, andtransketolase (TKL) would be blue in fungi andred in animals.

Yet even more importantly, for those glyco-lytic enzymes that have been studied from amito-chondriate protists (Markos et al., 1993; Henze etal., 1995, 1998; Keeling and Doolittle, 1997) a sim-ilar picture emerges, namely that amito-chondriate protists also possess eubacterialenzymes of the glycolytic pathway (Martin andMüller, 1998). Specific examples include gluco-kinase from Trichomonas vaginalis (Wu et al.,2001), PPi-PFK from Trichomonas vaginalis andGiardia lamblia (Mertens et al., 1998), aldolase fromGiardia lamblia (Henze et al., 1998) and fromTrichomonas vaginalis (Henze and Müller, unpub-lished), TPI from Giardia lamblia (Keeling andDoolittle, 1997; Martin, 1998), GAPDH fromTrichomonas vaginalis (Markos et al., 1993),Entamoeba histolytica and Giardia lamblia (Markoset al., 1993; Henze et al., 1995), and PGluM fromEntamoeba histolytica (Figure 27.1B).


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The endosymbiont hypothesis in its variousformulations and the archezoa hypothesis is ata loss to account for the observation that eu-karyotes have a eubacterial glycolytic pathway intheir cytosol. By contrast, the hydrogen hypoth-esis specifically predicts eukaryotes to have aeubacterial glycolytic pathway because the mechanism that it posits to have associated the mito-chondrial (hydrogenosomal) symbiont with itsH2-dependent host entails the acquisition by theautotrophic host of the symbiont’s heterotrophiclifestyle (glycolysis in particular) through endo-symbiotic gene transfer, a special case of hori-zontal gene transfer (Martin and Müller, 1998).

It is noteworthy that the only enzyme of theglycolytic pathway in eukaryotes that seems to bea direct inheritance from the archaebacterial hostlineage, enolase, is more similar to homologuesfrom methanogens than to homologues fromother eukaryotes (Hannaert et al., 2000), in linewith the prediction of the hydrogen hypothesisthat the host lineage should ultimately reflect amethanogenic ancestry (Martin and Müller,1998). This view is also supported by that findingthat methanogens are the only prokaryotes thatpossess true histones (Sandman and Reeve,1998). Also in line with the hydrogen hypothesisis the finding that some protists have even pre-served glycolytic enzymes in their mitochondria(Liaud et al., 2000). Furthermore in line with thepredictions of the hydrogen hypothesis isthe finding that a highly characteristic enzymeof hydrogenosomes, pyruvate:ferredoxin oxido-reductase (Müller, 1993), is found in the mito-chondria of Euglena gracilis and that the mito-chondrial and hydrogenosomal enzymes share acommon eubacterial origin (Rotte et al., 2001).

Horizontal gene transfer between free-living eubacteria adds an additional levelof complexity

Since the first edition of this book was pub-lished, it has become apparent that horizontalgene transfer between free-living eubacteria is avery widespread process, at least in evolution-arily recent times (Lawrence and Ochman, 1998;Doolittle, 1999; Eisen 2000; Ochman et al., 2000).Since horizontal gene transfer is well known

to occur at appreciable rates among free-livingprokaryotes today, we should assume it also tohave occurred in the distant past. This simplelogic is essential to keep in mind when consid-ering the origin of eukaryotic genes that wereacquired from eubacterial symbionts throughendosymbiotic gene transfer (Martin andSchnarrenberger, 1997; Martin, 1999a). Thereason is because very many of the eukaryoticgenes studied to date that clearly come fromeubacteria do not branch specifically with theirhomologues from cyanobacteria and α-proteo-bacteria, the antecedents of chloroplasts and mi-tochondria. The interpretation of such findingsrequires a bit of thought.

For example, in a recent survey of severalthousand Arabidopsis genes, all of 20 different se-quenced prokaryotic genomes sampled wouldhave appeared to have donated genes to theArabidopsis lineage, if the gene phylogenies areinterpreted at face value (Rujan and Martin,2001). In other words, for all 20 prokaryoticgenomes in that study (16 eubacteria and fourarchaebacteria), at least one gene tree wasobserved where the Arabidopsis nuclear genebranched with a homologue from the givengenome. At face value, that would suggest thatall 20 lineages of prokaryotes donated genes toArabidopsis. Had 40 different prokaryotic gen-omes been studied, then 40 different donorsto the Arabidopsis lineage would have been im-plied, if the trees are taken at face value.

But if we think things through in full and con-sider the process of horizontal gene transfer be-tween free-living prokaryotes as a continuumback through time, it becomes immediately evi-dent that it is unrealistic to expect all plant nu-clear genes that were donated by the antecedentof plastids to branch with homologues from con-temporary cyanobacteria, and it is unrealistic toexpect all genes that were donated to theeukaryotic lineage by the antecedent of mito-chondria to branch with α-proteobacterial homo-logues. This is shown in Figure 27.3 (see colorplates), which was modified from Martin (1999a).All available evidence indicated a single origin ofplastids (Martin et al., 1998; Moreira et al., 2000)and mitochondria (Gray et al., 1999). When thecyanobacterium that gave rise to plastids about1.5 billion years ago (Doolittle, 1997) entered into


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its symbiosis, it contained exactly one genome’sworth of genes (plus a plasmid or two, probably).Its free-living relative among the cyanobacteriathat existed then contained exactly the same setof genes. But the cyanobacterium that becamethe plastid was cut off from gene exchangewith other free-living prokaryotes, because itwas genetically isolated within the eukaryoticcell, a condition that persisted for another1.5 billion years to the present. By contrast, itsfree-living relatives were free to exchange theirgenes with other cyanobacteria and withother non-cyanobacterial prokaryotes for an-other 1.5 billion years. Exactly the same rea-soning applies to the α-proteobacterium thatgave rise to mitochondria, except that the free-living cousins of the mitochondrial (hydrogeno-somal) symbiont had even more time, about 2 bil-lion years (Doolittle, 1997), to exchange geneswith other prokaryotes, whereas the mitochon-drial symbiont did not.

Given that, let us consider the blazing speed(in terms of geological time) with which E. coli,as a well-studied example, has exchanged itsgenes with other eubacteria (Lawrence andOchman, 1998). Lawrence and Ochman (1998)estimated that E. coli has acquired foreign DNAat a rate of about 16 kb per million years overthe last 100 million years, and by inference, thatabout the same amount of DNA has been lostfrom its genome in return. The values for otherprokaryotes may be similar (Doolittle, 1999;Eisen, 2000; Ochman et al., 2000). If that ratewere to be projected back in time into thedepths of history where mitochondria and plas-tids arose, then the current E. coli genomewould not share any genes with the genomethat existed in ancestors of E. coli that lived 1 bil-lion years ago (Martin, 1999a).

Thus, it is extremely unlikely that any free-living prokaryote contains exactly the same setof genes as either the plastid symbiont and orthe mitochondrial symbiont (Martin andSchnarrenberger, 1997; Martin 1999a; Rujan andMartin, 2001). For exactly the same reasons, it isextremely likely that many of the genes that arecurrently found in eukaryotic genomes andthat are clearly acquisitions from eubacteria,probably come from the ancestors of mitochon-dria (hydrogenosomes) and the ancestors of

plastids, even though they do not appear tostem from α-proteobacteria and cyanobacteriarespectively. Conversely, one can expect some(or many) genes that were donated to the nu-cleus from mitochondria and chloroplasts not tobranch with α-proteobacterial or cyanobacterialhomologues. Rather, they will branch with anynumber of eubacterial groups, depending uponwhere these ancestrally donated genes haveended up in contemporary eubacteria. This isthe essence of what is shown in Figure 27.3(Martin, 1999a; Rujan and Martin, 2001).

CONCLUSION

Horizontal gene transfer is a very powerful pro-cess in evolution when it comes to shaping thegene content of genomes, both prokaryotic andeukaryotic. Plastids and mitochondria donatedmany genes to eukaryotic genomes. Some of theproducts of those genes are reimported as pro-teins into the organelle, many others arenot – rather they are imported into otherorganelles or localized in the cytosol or the nu-cleus, which is not an organelle. Contrary towhat was believed 20 years ago (and is some-times still believed today), the compartment-ation of a protein is not a good indicator of itsevolutionary origin. Molecular phylogeneticsgenerally has a hard time coming to grips withthe problem of horizontal gene transfer becauseit makes it more difficult to draw direct infer-ences about the evolutionary past from thephylogenies of contemporary genes. But the sit-uation may not be so dire. If we do not allowourselves to digress into the realm of descriptivehypothesis-free science, that is if we have goodbiological theories with which to interpret mo-lecular phylogenies and which we can test withmolecular phylogenies, then horizontal genetransfer will probably enrich, rather thanhamper, our understanding of life’s history, inparticular the origin of eukaryotic genes.

ACKNOWLEDGMENTS

We thank Miklos Müller for numerousstimulating discussions and Marianne Limpert


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for help in preparing the manuscript. Gen-erous financial support from the Deut-sche Forschungsgemeinschaft is gratefullyacknowledged.

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FIGURE 27.2 (See following page for caption.)

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FIGURE 27.2 (On previous page.) Summary of gene phylogenies for enzymes of compartmentalized sugarphosphate metabolism in plants. Suggested evolutionary origins for the nuclear genes are color-coded. Enzymesregulated through the thioredoxin system are indicated. Many enzymes in the figure are allosterically regulated,but no allosteric regulation is indicated here. Enyzme abbreviations are: FBA fructose-1,6-bisphosphate aldolase;FBP fructose-1,6-bisphosphatase; GAPDH glyceraldehyde-3-phosphate dehydrogenase; PGK 3-phospho-glycerate kinase; PRI ribose-5-phosphate isomerase; PRK phosphoribulokinase; Rubisco ribulose-1,5-bisphosphatecarboxylase/oxygenase; RPE ribulose-5-phosphate 3-epimerase; SBP sedoheptulose-1,7-bisphosphatase; TKLtransketolase; TPI triosephosphate isomerase; TAL transaldolase; GPI glucose-6-phosphate isomerase; G6PDHglucose-6-phosphate dehydrogenase; 6GPDH 6-phosphogluconate dehydrogenase; PGluM phosphogluco-mutase; PGM phosphoglyceromutase; PFK phosphofructokinase (pyrophosphate and ATP-dependent); ENOenolase; PYK pyruvate kinase; PDC pyruvate dehydrogenase complex (E1, E2, E3 components), T translocator.PDC is a multienzyme complex, but only one set of components is drawn here. Note that chloroplast isoenzymes ofPGM, ENO, and PYK have not been demonstrated in spinach leaves, but for convenience we have included thoseenzymes in this figure, since they have been well characterized in the plastids of other higher plants (Plaxton, 1996).For further details see Martin and Schnarrenberger (1997), Martin and Herrmann (1998), Nowitzki et al. (1998) andKrepinsky et al. (2001).

FIGURE 27.3 (Opposite.) A tree of genomes. Each prokaryotic genome is represented as a single colored line,different colors symbolize different groups of prokaryotes. A working hypothesis for the origin of eukaryoticgenes as outlined primarily in Martin and Müller (1998) and taking lateral gene transfer into account (modifiedfrom Martin, 1999a). The figure extends symbiotic associations (merging of genomes into the same cellularconfines is indicated by the merging of colored lines) to include schematic indication of several independentsecondary symbioses for the acquisition of plastids during eukaryotic history (Martin et al., 1998; Zauner et al.,2000). Importantly, among eukaryotes, colored lines indicate merely that prokaryotic genomes existed at onetime within the cellular confines of a given eukaryotic lineage, not that they have persisted to the present as anindependently compartmented genome (because most genes from organelles are transferred to the nucleus). Forexample some eukaryotes with secondary symbionts are schematically indicated with six lines, but only havefour distinctly compartmented genomes. Similarly, eukaryotes that lack mitochondria apparently possessedsuch organelles in the past but only have one genome – that in the nucleus (for example Giardia, Trichomonas, andEntamoeba, see text). Furthermore it is important to note that mitochondrion-lacking eukaryotes have arisenthrough loss of the organelle in many independent lineages (Embley and Martin, 1998; Hashimoto et al., 1998;Roger, 1999). In the enlargement, lateral gene transfer between eubacteria prior to – and implicitly, but not shown,subsequent to – the origin of mitochondria (blue lines) and plastids (green lines) is schematically represented.Genomes are represented as heavy lines, individual gene transfer events (regardless of possible numbers ofgenes involved) as thin lines. The phylogeny of eukaryotes indicated is mostly schematic, containing variouselements from van der Peer et al. (1996), Keeling and Palmer (2000), Martin et al. (1998) and other sources, and isnot intended to be close to correct. The various schematic plastid organizational types are shown merely toindicate that dramatic differences in organelle structure can arise from a single ancestral symbiotic state.

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free-livingEubacteria

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or Mitochondria, orno ATP-Producing

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horizontal gene transfer || endosymbiotic gene transfer

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