En­er­get­ics of the Eu­kary­otic Edge

by Franklin M. Harold

The most con­spic­u­ous fea­ture in the land­scape of cell evo­lu­tion is the tremen­dous rift that sep­a­rates eu­kary­otes from prokary­otes. This is not ap­par­ent at the level of ri­bo­so­mal RNA se­quences, or of mol­e­c­u­lar bi­ol­ogy in gen­eral, but leaps to the eye of any­one in­trigued by form, func­tion and evo­lu­tion­ary po­ten­tial. Prokary­otes have been bio­chem­i­cally most in­ven­tive, and found ac­cess to all the prac­ti­ca­ble en­ergy sources our planet has to of­fer. It's a good rule of thumb that, if a chem­i­cal re­ac­tion yields suf­fi­cient en­ergy to sup­port life, a prokary­ote ex­ists that ex­ploits it. But when judged by their mor­phol­ogy and or­ga­ni­za­tion, prokary­otes seem to have ad­vanced lit­tle be­yond their fos­sil an­ces­tors of 2 to 3 bil­lion years ago. Some, it is true, have at­tained struc­tural and be­hav­ioral com­plex­ity be­yond the norm: cyanobac­te­ria and planc­to­mycetes with their in­ter­nal mem­branes come to mind, and so do myxobac­te­ria with their elab­o­rate fruit­ing bod­ies and wolf-pack hunt­ing habit. Still, these pale by com­par­i­son with even the plainest of eu­kary­otic pro­tists, whose cells are typ­i­cally a thou­sand times larger and stuffed with func­tional ma­chin­ery. It is al­most seems as though the prokary­otes made re­peated starts up the lad­der of com­plex­ity, but al­ways fell short. By con­trast eu­kary­otes, de­spite their mea­ger meta­bolic reper­toire, burst what­ever con­straints ham­pered prokary­otes to ex­per­i­ment with the op­por­tu­ni­ties af­forded by greater cell size and more elab­o­rate or­ga­ni­za­tion. Just what is it that made the eu­kary­otic mode of life so much more "evolv­able" than the prokary­otic one?

Typ­i­cal prokary­otic (a) and eu­kary­otic (b) cells. Source

Evolv­abil­ity is an ab­stract term that refers to "the ca­pac­ity to gen­er­ate her­i­ta­ble, se­lec­table phe­no­typic vari­a­tion" (1), and some­times more broadly to the propen­sity to evolve novel struc­tures (2). Marc Kirschner and John Ger­hart, whose de­f­i­n­i­tion I have just ap­pro­pri­ated, credit the con­spic­u­ous evolv­abil­ity of meta­zoa to the flex­i­bil­ity of the de­vel­op­men­tal processes that me­di­ate be­tween geno­type and phe­no­type. Loose reins also rank among the sig­nif­i­cant dif­fer­ences be­tween prokary­otic cells and eu­kary­otic ones: as a rule, the lat­ter have many more genes and much ex­tra DNA, more tol­er­ant reg­u­la­tion of gene ex­pres­sion, many more mov­ing parts and a more fluid phys­i­ol­ogy. These are surely im­por­tant dif­fer­ences, but they look like con­se­quences of the dis­tinc­tive evo­lu­tion­ary strate­gies pur­sued by the two kinds of cells, rather than the cause thereof. Nor does it make sense to at­tribute the dif­fer­ence to some sin­gu­lar and crit­i­cal in­ven­tion, such as nu­clear mem­branes or lin­ear chro­mo­somes. Though char­ac­ter­is­tic of eu­kary­otic cells, both are found in some prokary­otes as well; even en­do­cy­to­sis has re­cently been doc­u­mented in planc­to­mycetes (3).

 A more con­vinc­ing ar­gu­ment links the gulf that di­vides prokary­otes from eu­kary­otes to their dis­tinct ways of or­ga­niz­ing the pro­duc­tion of use­ful en­ergy. In prokary­otes en­ergy gen­er­a­tion is a func­tion of the plasma mem­brane, whereas eu­kary­otes as­sign it to spe­cial­ized com­po­nents, the mi­to­chon­dria and chloro­plasts. This greatly ex­pands the mem­brane sur­face avail­able for en­ergy trans­duc­tion by ion cur­rents, while free­ing the plasma mem­brane for other tasks. How­ever, as Nick Lane and William Mar­tin ex­plain in a stim­u­lat­ing pa­per (4), this is just the be­gin­ning of the story, for that anatom­i­cal dif­fer­ence has un­ex­pected evo­lu­tion­ary im­pli­ca­tions. In prokary­otes, the en­ergy gen­er­ated by each in­di­vid­ual cell sup­ports the out­put of its own genome; as much as three quar­ters of that en­ergy is re­quired just to ex­press ge­nomic in­for­ma­tion by way of pro­tein syn­the­sis. By con­trast, in eu­kary­otic cells the en­ergy pro­duced by hun­dreds or even thou­sands of mi­to­chon­dria, each one a prokary­otic power pack, is put at the ser­vice of a sin­gle cen­tral genome. In con­se­quence, a eu­kary­otic genome gov­erns far more en­ergy than a prokary­otic one. This al­lowed eu­kary­otic genomes to ex­pand, lay­ing the foun­da­tions for the spec­tac­u­lar dif­fer­ence in cel­lu­lar com­plex­ity. Lane and Mar­tin ar­gue that the rise of the eu­kary­otes was due to the ac­qui­si­tion of mi­to­chon­dria at a very early stage in their evo­lu­tion; and fur­ther­more, that the only way struc­turally and func­tion­ally com­plex cells could have made an ap­pear­ance was by en­slav­ing en­dosym­bionts.

Let a few num­bers taken from that pa­per bol­ster the the­sis. When ex­pressed on the ba­sis of mass, the mean meta­bolic rates of aer­o­bic eu­bac­te­ria and pro­to­zoa are not very dif­fer­ent: 0.19 and 0.06 W/g, re­spec­tively (one watt cor­re­sponds to one joule per sec­ond). But their cel­lu­lar masses are very dif­fer­ent in­deed, typ­i­cally 2.6 x 10 ^-12g for the bac­terium and 40,000 x 10^-12 g for the pro­to­zoan. In con­se­quence, a pro­to­zoan cell has much more power at its com­mand than a bac­te­r­ial one: 2300 pW per cell, com­pared to 0.49 pW. Eu­kary­otic cells made use of that abun­dant en­ergy to ex­pand their genomes by or­ders of mag­ni­tude: the mean hap­loid DNA con­tent is 6 megabases for a prokary­otic cell, 3000 megabases for a pro­to­zoan. (mean gene num­bers are 5000 and 20,000, re­spec­tively, though both prokary­otic and eu­kary­otic genomes vary over a wide range). Even so, the en­ergy avail­able per gene is far greater for eu­kary­otes than for prokary­otes, 57 fW ver­sus 0.03 fW per gene (other ways of ex­press­ing the dif­fer­ence make the dis­par­ity even larger). The mi­to­chon­dria that power a eu­kary­otic cell still har­bor a min­i­mal genome, a rem­nant of the genome that came in with the an­ces­tral en­dosym­biont; most of those genes were ei­ther lost or trans­ferred to the host's nu­cleus. Tak­ing or­ganel­lar genes into ac­count makes lit­tle dif­fer­ence to the es­ti­mate of the power avail­able per gene. Ev­i­dently, eu­kary­otic cells have "en­ergy to burn", more than suf­fi­cient to evolve many new pro­tein fam­i­lies, to ex­plore so­phis­ti­cated ways to reg­u­late their pro­duc­tion and put them to work in elab­o­rate phys­i­o­log­i­cal processes that would be be­yond the means of prokary­otic cells.

Lane and Mar­tin draw an in­struc­tive com­par­i­son be­tween the en­ergy bud­gets of a pro­to­zoan cell and a gi­ant prokary­ote, such as Epu­lop­is­cium fishel­sonii, sev­eral times the size of Para­me­cium. A cell of Epu­lop­is­cium is a con­sor­tium of some 200,000 full-fledged nu­cleoids, each re­liant upon a share of the en­ergy gen­er­ated by the com­mu­nal plasma mem­brane. Re­pro­duc­tion re­quires the cell to du­pli­cate 760,000 megabases of DNA, com­pared to 6000 megabases for a pro­to­zoan cell of com­pa­ra­ble size. Epu­lop­is­cium ob­vi­ously gen­er­ates suf­fi­cient en­ergy to re­pro­duce, but will have none to spare on a quest for struc­tural and func­tional com­plex­ity.

Could one imag­ine some way for prokary­otes to com­part­men­tal­ize their en­ergy pro­duc­tion in small pods, and thereby aug­ment the genome's power sup­ply with­out go­ing to all the bother of do­mes­ti­cat­ing en­dosym­bionts? Yes, one could, but bac­te­ria have not fol­lowed that path, and Lane and Mar­tin ar­gue that in re­al­ity no such op­tion was avail­able. The rea­son is that the small genomes re­tained by both mi­to­chon­dria and chloro­plasts per­form an es­sen­tial func­tion. Main­tain­ing a steady flux of elec­trons through the res­pi­ra­tory (and pho­to­syn­thetic) re­dox chains re­quires the cell to make ad­just­ments and re­pairs to in­di­vid­ual or­ganelles as needed, and that can only be done un­der the con­trol of a genome lo­cal­ized to the par­tic­u­lar or­ganelle (5). That kind of ar­chi­tec­ture can only be achieved by start­ing with en­dosym­bionts, en­slaved and put to work as com­po­nents of a larger com­mu­nity.

These ideas have im­pli­ca­tions for one of the thorni­est is­sues in cell evo­lu­tion, the ori­gin of eu­kary­otic cells. In the con­ven­tional view, mi­to­chon­dria came late into a phago­cytic cell, de­scended from the eu­bac­te­r­ial stem, that was al­ready well on its way to at­tain­ing eu­kary­otic or­ga­ni­za­tion (6,7). Lane and Mar­tin re­ject that po­si­tion in fa­vor of the hy­poth­e­sis that the first step in eu­karyo­ge­n­e­sis was the fu­sion or merger of an ar­chae­bac­terium with a eu­bac­terium (8,9). The for­mer made large con­tri­bu­tions to both the cy­to­plasm and the nu­clear genome, the lat­ter be­came the pre­cur­sor of mi­to­chon­dria, and their in­creas­ingly in­ti­mate part­ner­ship pro­duced the eu­kary­otic cell. An es­sen­tial el­e­ment of their the­sis is that mi­to­chon­dria came early and were a pre­req­ui­site to the evo­lu­tion of eu­kary­otic or­ga­ni­za­tion. I must re­serve judg­ment about parts of this pro­posal: I have al­ways doubted that merger of prokary­otic cells, and would note that an early ac­qui­si­tion of mi­to­chon­dria is en­tirely con­sis­tent with Carl Woese's orig­i­nal view that the prog­en­i­tor of the eu­kary­otes rep­re­sents one of the pri­mary lines of cel­lu­lar de­scent. The pri­mor­dial com­mu­nity of prokary­otes would surely have had a niche for some sort of prim­i­tive scav­enger or preda­tor (pre­sum­ably re­lated to the Ar­chaea), which would make the per­fect host for en­dosym­bionts (10); we proud eu­kary­otes must ac­knowl­edge hum­ble an­ces­try! Be that as it may (and we will prob­a­bly never know for sure), the the­sis that mi­to­chon­dria came early and were re­quired for the evo­lu­tion of the full eu­kary­otic or­der has, to my ears, the ring of an im­por­tant truth.

Let me not leave those evolv­able eu­kary­otes with­out not­ing that the role of en­er­get­ics in their emer­gence was per­mis­sive, not pre­scrip­tive: a gen­er­ous sup­ply of en­ergy made great things pos­si­ble, but man­dated none of them. We are still obliged to spec­ify the fea­tures of eu­kary­otic or­ga­ni­za­tion that nat­ural se­lec­tion fa­vored, and the mol­e­c­u­lar in­ven­tions that marked the way. That task has not yet been fully ac­com­plished, but the ar­gu­ment that pre­da­tion based on phago­cy­to­sis is key to the rise of the eu­kary­otes (6,7) seems to me sound. Prokary­otes, by con­trast, are con­strained by lim­i­ta­tions on the en­ergy avail­able to the genome, which bent their evo­lu­tion into quite dif­fer­ent chan­nels. In their case, nat­ural se­lec­tion fa­vored small and spare cells with stream­lined genomes, rapid re­pro­duc­tion, lit­tle su­per­flu­ous DNA and tightly dis­ci­plined reg­u­la­tion of gene ex­pres­sion. March­ing un­der the ban­ner Small is Beau­ti­ful they flour­ished, mul­ti­plied and in­her­ited the earth. From any point of view ex­cept that of a eu­kary­otic chau­vin­ist, it's still a prokary­otic world.

Ref­er­ences

1. Kirschner, M., and J. Ger­hart. 1988. Evolv­abil­ity. Proc. Natl. Acad. Sci. USA 95: 8420 – 8427.

2. Pigli­ucci, M. 2008. Is evolv­abil­ity evolv­able? Na­ture Rev. Ge­net­ics 9: 75 –82.

3. Lon­hi­enne, T. G., et al. 2010. En­do­cy­to­sis-like pro­tein up­take in the bac­terium Gem­mata ob­scuriglob­u­los. Proc. Natl. Acad. Sci. USA 107: 12883 — 12888.

4. Lane, N., and W. Mar­tin. 2010. The en­er­get­ics of genome com­plex­ity. Na­ture 467: 929 – 934.

5. Allen, J. F. 2003. The func­tion of genomes in bioen­er­getic or­ganelles. Phi­los. Trans. Roy. Soc. B 358: 19 – 38.

6. Cav­a­lier-Smith, T. 2002. The phagotrophic ori­gin of eu­kary­otes and phy­lo­ge­netic clas­si­fi­ca­tion of pro­to­zoa. In­ter­nat. J. Sys. Evol. Mi­cro­biol. 52: 297 — 354.

7. de Duve, C. 2007. The ori­gin of eu­kary­otes: a reap­praisal. Na­ture Rev. Ge­net­ics 8: 395 – 403.

8. Em­b­ley, T. M., and W. Mar­tin. 2006. Eu­kary­otic evo­lu­tion, changes and chal­lenges. Na­ture 440: 623 – 630.

9. Cox, C. J., et al. 2008. The ar­chae­bac­te­r­ial ori­gin of eu­kary­otes. Proc. Natl. Acad. Sci. USA 105: 20356 – 20361.

10. Kur­land, C. G., Collins, L. J. and D. Penny. 2006. Ge­nomics and the ir­re­ducible na­ture of eu­kary­otic cells. Sci­ence 312: 1011 – 1014.

Franklin M. Harold, De­part­ment of Mi­cro­bi­ol­ogy, Uni­ver­sity of Wash­ing­ton, Seat­tle, WA 98195. E‑Mail: frankharold@earthlink.net