Com­ments on Bac­te­r­ial Mi­to­sis: What's Tak­ing So Long?

by Merry & Elio

This mini-es­say gar­nered some par­tic­u­larly in­sight­ful and provoca­tive com­ments. We think they de­serve their own post­ing. We hope the dis­cus­sion con­tin­ues.

Saman­tha Or­chard

I think it is in­ter­est­ing that while quite a bit is now known about the seg­re­ga­tion of some bac­te­r­ial plas­mids (as de­scribed in this blog en­try), rel­a­tively lit­tle is known about bac­te­r­ial chro­mo­some seg­re­ga­tion. I won­der if it isn't a com­bi­na­tion of the small size of the bac­te­ria (as noted above) and the fact that any pro­teins re­quired for chro­mo­some seg­re­ga­tion are es­sen­tial for cell vi­a­bil­ity and are there­fore less eas­ily stud­ied? Also, it should be noted that a few labs have pro­posed that bac­te­r­ial chro­mo­some seg­re­ga­tion might oc­cur with­out the need for spe­cific seg­re­ga­tion pro­teins.

For ex­am­ple, see the work of Suck­joon Jun and Bela Mul­der who pro­pose a role for en­tropy in chro­mo­some seg­re­ga­tion. Con­rad Woldringh is an­other per­son I know of who is a pro­po­nent of a less ac­tive method of chro­mo­some seg­re­ga­tion, one in­volv­ing transer­tion (com­bined transcript­ion, trans­la­tion and in­ser­tion of the pro­teins be­ing trans­lated into the mem­brane caus­ing a "tug" on the chro­mo­some) and dif­fu­sion of the daugh­ter chro­mo­somes due to phase ex­clu­sion from the solutes in the cy­to­plasm.

Elio replies:

Many thanks for point­ing out that cur­rently there is in­ter­est in a purely phys­i­cal model for bacte­rial chro­mo­some seg­re­ga­tion, one not in­volv­ing a spe­cial ma­chin­ery. Surely this will be a hot area of de­bate. Stay tuned.

 

Paul Or­win

This is a very in­ter­est­ing topic, and I have no ex­pla­na­tion for why it has lagged eu­kary­otic stud­ies. Per­haps be­cause mi­cro­bial ge­netic tech­niques are not well suited to study­ing par­ti­tion de­fects? Hard to say if that is true, but mol­e­c­u­lar and bioin­for­matic strate­gies seem solid. It could a combi­nation of bias (bac­te­ria split sim­ply, by fis­sion) and dif­fi­culty (we never get chro­mo­some par­ti­tion mu­tants in screens, or we mis s the phe­no­type). Speak­ing of new stud­ies on this topic, here's one that is in JBact ahead of print right now:

Yoshi­haru Ya­maichi, Michael A. Fo­gel, Sarah M. McLeod, and Mon­ica P. Hui. Dis­tinct cen­tromere-like parS sites on the two chro­mo­somes of vib­rio species.

I just skimmed it, but it looks like they used the known ParAB gene func­tion to iden­tify the chro­mo­so­mal sites re­quired for cor­rect par­ti­tion of both chro­mo­somes. As you said, a hot topic.

Apalazzo

I would say that a proper study of mi­to­sis re­quires knowl­edge of the cy­toskele­ton and the abil­ity to im­age the sub­ject in ques­tion (you might even ar­gue that the ad­vent of imag­ing is cru­cial for the un­der­stand­ing of cel­lu­lar or­ga­ni­za­tion.) Imag­ing and the study of the cy­toskele­ton are both eas­ier in euks in com­par­i­son to proks.

Con­rad Woldringh

Bac­te­r­ial Mi­to­sis: What's Tak­ing So Long? Those who agree with this ques­tion have to ex­ert more pa­tience for two rea­sons:

First, be­cause, in my view, there is no such sim­ple thing as "bac­te­r­ial mi­to­sis". The term "mi­totic-like seg­re­ga­tion" is used, some mi­cro­bi­ol­o­gists told me, be­cause the ter­mi­nol­ogy of G1, S, G2 and M phases makes it eas­ier to pub­lish in Eu­kary­otic-Cell-like jour­nals.
 

The sec­ond rea­son is that the eu­kary­otic process of strand res­o­lu­tion within the cohesin/conden­sin com­plexes, with which the process of bac­te­r­ial seg­re­ga­tion can bet­ter be com­pared, is far from un­der­stood. In a re­view of 2002 ("Seg­re­gat­ing sis­ter genomes: the mol­e­c­u­lar bi­ol­ogy of chromo­some sep­a­ra­tion". Sci­ence 297: 559–565) Kim Nas­myth noted that sis­ter chro­matid dis­en­gage­ment "oc­curs in the com­plete ab­sence of mi­cro­tubules and yet is ca­pa­ble of sep­a­rat­ing sis­ter se­quences by up to 0.5 µm." And he fur­ther re­marks that this first phase in eu­kary­otic DNA seg­re­ga­tion may in­volve processes sim­i­lar to bac­te­r­ial nu­cleoid seg­re­ga­tion.

This com­par­i­son was made ear­lier (see Woldringh, C.L., and R. Van Driel. 1999. The Eu­kary­otic Per­spective: Sim­i­lar­i­ties and dis­tinc­tions be­tween pro- and eu­kary­otes. p. 77–90. In R.L. Charlebois (ed.), Or­ga­ni­za­tion of the prokary­otic genome. Chap­ter 5. Amer­i­can So­ci­ety for Mi­cro­bi­ol­ogy, Wash­ington, D.C.). In this chap­ter we em­pha­sized that the high amount of tran­scrip­tion oc­cur­ring across the eu­kary­otic (mam­malian) chro­mo­some (see, for in­stance: The ENCODE Project Consort­ium. 2007. Na­ture 447: 799–816.) could play a role in strand sep­a­ra­tion just as has been sug­gested for bac­te­r­ial seg­re­ga­tion (see post by Saman­tha Or­chard, May 14, 2007).

For me the ques­tion is how within the cell DNA sis­ter-strands in­ter­act when a repli­ca­tion bub­ble is formed. If they sep­a­rate un­der the in­flu­ence of en­tropic forces as sug­gested by Jun and Mul­der (2006. PNAS 103: 12388–12393), how long can this de-mix­ing last? Con­sid­ered as a phys­i­cal poly­mer prob­a­bly not long. But as a "bi­o­log­i­cal poly­mer", where the du­pli­cated strands be­come decor­ated with DNA bind­ing pro­teins with dif­fer­ent and tran­sient ac­tiv­i­ties like lig­a­tion, tran­scrip­tion or su­per­coil for­ma­tion, the ini­tial de-mix­ing could be­come pro­longed and sta­bi­lized, gen­er­at­ing se­gregation.

Men­tion­ing these processes re­minds me of the re­marks by Franklin Harold (his post of May 28, 2007) about spa­tial or self-or­ga­ni­za­tion ariz­ing from the in­ter­ac­tions among large num­bers of gene prod­ucts. This is "sta­tis­ti­cal me­chan­ics"! It is not the eas­i­est physics for a bi­ol­o­gist (see, for in­stance: Odijk, T. 1998. Os­motic com­paction of su­per­coiled DNA into a bac­te­r­ial nu­cleoid. Bio­phys. Chem.  73: 23–30). To get a feel­ing for this self-or­ga­ni­za­tion of macro­mol­e­cules in ei­ther eu­karyotes or prokary­otes we have to learn sta­tis­ti­cal ther­mo­dy­nam­ics and need time and pa­tience to un­der­stand its old and dif­fi­cult con­cepts, that can still hardly be ap­plied to the com­plex­ity of cells.

Robert Mur­ray

Here is a his­tor­i­cal note dri­ven by the rev­e­la­tion that there is in­volve­ment of a mo­tor actin-like pro­tein in the ag­gre­ga­tion of both a bac­te­r­ial chro­mo­some and ac­com­pa­ny­ing large plas­mid. This awak­ens mem­o­ries of the 1950's polemic about di­rect nu­clear di­vi­sion ver­sus a mi­to­sis-like chro­mo­so­mal bal­let. It was a mat­ter of in­tr­pre­ta­tion of im­ages in fixed and stained prepa­ra­tions. Model species (e.g., B. sub­tilis) showed fairly com­pact nu­clear bod­ies that some­how formed two sim­i­larly shaped bod­ies dur­ing cell di­vi­sion; other model species (e.g., B. mega­terium) showed con­stel­la­tions of chro­ma­tinic bits in a patch form of nu­cleus. Two views re­sulted: C.F. Robi­now con­tended that gen­er­ally the nu­clei be­haved as a unit and di­vided di­rectly while E.D. De­la­mater con­tended that the seg­re­ga­tion was more likely rep­re­sented by the patch forms in which se­lect nu­clei ex­em­pli­fied stages in the clas­si­cal mi­totic cy­cle. Each of them had stu­dents and sup­port­ers and their var­i­ous in­ter­pre­ta­tions gen­er­ated heated ar­gu­ments en­ter­tain­ing enough for cy­to­log­i­cal pa­pers to be given in the biggest meet­ing rooms. It went on for years but in the end ge­netic stud­ies were con­vinc­ing that the main model species (in­clud­ing by then E. coli) had only a sin­gle link­age group. The ar­gu­ment col­lapsed and there was a for­mal with­drawal of the con­cept of a mi­to­sis process in bac­te­ria.

So now two ag­ing, friendly blog­gers who were dis­posed on one side or the other in the 50's are faced with a dilemma. Was each side par­tially right or par­tially wrong?  Any­way, is this the proper ap­pli­ca­tion of the term mi­to­sis, which to some of us is the de­scrip­tive term for a chore­o­graphed bal­let of eu­cary­otic chro­mo­somes as­sisted by cen­tri­oles and spin­dle struc­tures? Maybe it does not mat­ter: they move any­way and the mech­a­nism has at least one el­e­ment that re­minds us of how mi­to­sis works.