Tal­mu­dic Ques­tion #30

I be­lieve that ALL bac­te­ria em­ploy com­plex reg­u­la­tory processes to con­trol their gene ex­pres­sion (we only know about these processes in the few ex­ten­sively stud­ies bugs). I tell my stu­dents this is be­cause bac­te­ria can­not af­ford to make any mis­takes in gene ex­pres­sion that would re­sult in un­prof­itable ex­pen­di­ture of en­ergy or non­adap­tive changes to their en­vi­ron­ment.

Be­cause I like to be a con­trar­ian; in what sense do they have a lot of reg­u­la­tory mech­a­nisms? This is sim­i­lar to what Tim said, but I'm sure no one on this site would un­der­es­ti­mate the com­plex­ity of mi­cro­bial lifestyles! If the ques­tion is in­ter­preted more nar­rowly as why have reg­u­la­tion at all lev­els, in­stead of just tran­scrip­tional or trans­la­tional, or al­loster­i­cally, I'd imag­ine it is more or less the dif­fer­ence be­tween need­ing to act fast (pro­tein level reg­u­la­tion of motil­ity, for ex­am­ple) vs. act­ing carefully/judiciously, i.e. the dif­fi­cult and irreversible(ish) de­ci­sion to be­come a spore. Dif­fer­ent modes for dif­fer­ent choices, and all that. We all know that small isn't sim­ple....

The rea­son that comes to the minds of many for why reg­u­late cel­lu­lar processes would be to save en­ergy. Any ac­tion a cell de­cides to take will ex­pend en­ergy and re­sources. Whether the cell is repli­cat­ing or tran­scrib­ing DNA, trans­lat­ing a pro­tein, or sim­ply de­grad­ing cel­lu­lar com­po­nents that are no longer needed, en­ergy is be­ing used. The real ques­tion is whether or not the en­ergy ex­pended is sub­stan­tial com­pared to the to­tal en­ergy sup­ply of the cell. I be­lieve that the en­ergy used up is a small enough frac­tion of what the cell has at its ex­pense, that reg­u­la­tion is re­ally not about sav­ing en­ergy. Rather I think reg­u­la­tion is nec­es­sary in or­der to adapt and thrive in a va­ri­ety of en­vi­ron­ments in or­der to pro­mote sur­vival. A cell is pro­vided with a num­ber of sig­nals at any given time. It is the pri­or­i­ti­za­tion in re­sponse to these sig­nals that de­ter­mines what en­vi­ron­ment and what con­di­tions the cell will adapt it­self to. A prime ex­am­ple of such pri­or­i­ti­za­tion is the Lac Operon. A cell ben­e­fits the most from the up­take of glu­cose and with­out reg­u­la­tion, if glu­cose and lac­tose were both around there may be no dis­tinc­tion made be­tween the two sugar en­ergy sources. In or­der to ben­e­fit the most from its en­vi­ron­ment, a cell should up­take and use the glu­cose rather than the lac­tose. Aside from the pri­or­i­ti­za­tion of which food source to choose to pro­vide the most ben­e­fit, there are more se­ri­ous con­se­quences of a lack of reg­u­la­tion. In times of star­va­tion, a cell can choose to turn on motil­ity or sporu­late. Sporu­la­tion is a com­mit­ted path­way that a cell can­not re­verse. If a cell were to en­ter this path­way at the wrong time it would re­sult in the death of the cell rather than its sur­vival via a spore.
In or­der to pri­or­i­tize such cel­lu­lar events, there must be reg­u­la­tion at every pos­si­ble level. There must be reg­u­la­tion at the level of tran­scrip­tion so gene tran­scripts that are not needed for the cur­rent en­vi­ron­ment are not float­ing around within the cy­to­plasm. I be­lieve this level could be more lax as mak­ing a tran­script does not guar­an­tee its trans­la­tion. Reg­u­la­tion at the level of trans­la­tion should be stricter as un­nec­es­sary pro­teins act­ing within the cy­to­plasm will al­ter pri­or­i­ti­za­tion or slow a switch to a new nu­tri­ent or en­vi­ron­men­tal stim­u­lus.
In short, a cell needs a va­ri­ety of reg­u­la­tory mech­a­nisms at every level in or­der to pri­or­i­tize its ac­tiv­i­ties in or­der to adapt to its sur­round­ings and pro­long its life.
Paula Pat­ter­son (Stu­dent, In­te­gra­tive Mi­cro­bi­ol­ogy course)

Bac­te­ria pos­sess a mul­ti­tude of reg­u­la­tory pro­teins (ex. ki­nase, phos­phatases just to name a cou­ple) that are re­spon­si­ble for en­sur­ing their abil­ity to con­trol their struc­ture, func­tion, dif­fer­en­ti­a­tion and adap­ta­tion to en­vi­ron­men­tal con­di­tions. In ad­di­tion many of these reg­u­la­tory pro­teins have over­lap­ping func­tions with other reg­u­la­tory pro­teins. This leads one to ask the ob­vi­ous ques­tion – why would a bac­terium want so many reg­u­la­tory pro­teins and why have reg­u­la­tory pro­teins with over­lap­ping func­tions?
The sec­ond half of this ques­tion is easy to an­swer. Hav­ing two reg­u­la­tory pro­teins with over­lap­ping func­tions en­sures that the proper reg­u­la­tion con­tin­ues to oc­cur even in the ab­sence of one of the reg­u­la­tory pro­teins. For ex­am­ple the syn­the­sis of ℗ppGpp is reg­u­lated by two pro­teins: RelA and SpoT. In the ab­sence of RelA the syn­the­sis of ℗ppGpp still oc­curs and is still de­tected in the cell thanks to SpoT. The over­lap­ping func­tion of SpoT en­sures that ℗ppGpp ex­pres­sion re­mains "nor­mal" un­der nu­tri­ent rich and nu­tri­ent poor con­di­tions, thus al­low­ing the cell to re­spond ac­cord­ingly. There­fore, over­lap­ping reg­u­la­tory pro­teins func­tion to en­sure the proper reg­u­la­tion of nu­mer­ous cel­lu­lar processes es­sen­tial for bac­te­r­ial sur­vival.
The first half of the ques­tion asks, why would a bac­terium want so many pro­teins? Nu­mer­ous bac­te­r­ial pro­teins have been im­pli­cated to per­form es­sen­tial func­tions in fairly sim­ple tasks such as cell growth and di­vi­sion. One pos­si­bil­ity for the abun­dance of so many bac­te­r­ial pro­teins is to en­sure that the ex­e­cuted task is be­ing per­formed cor­rectly. For ex­am­ple, each pro­tein in the RNA tran­scrip­tion com­plex per­forms func­tions in en­sur­ing proper gene ex­pres­sion (ex. al­ter­na­tive sigma fac­tors rec­og­niz­ing el­e­ments in the pro­mot­ers of stress re­sponse genes). The loss of one of these fac­tors could have a sig­nif­i­cant neg­a­tive im­pact on cell sur­vival. An­other rea­son why there are so many bac­te­r­ial pro­teins is to en­sure that bac­te­r­ial tasks are ex­e­cuted only when re­quired. For ex­am­ple, in­duc­tion of the stress re­sponse path­ways oc­curs via a sig­nal­ing cas­cade event in­volv­ing nu­mer­ous pro­teins and re­sult­ing in a change in gene ex­pres­sion. Each of these pro­teins in the sig­nal­ing cas­cade event could func­tion as a check­point to en­sure that un­nec­es­sary changes in gene ex­pres­sion do not oc­cur. A fi­nal rea­son why bac­te­ria have so many pro­teins may re­flect the abil­ity of the bac­terium to "fine tune" cel­lu­lar processes to al­low for op­ti­mal sur­vival. Hav­ing the abil­ity to change a sin­gle pro­tein in a pro­tein com­plex may op­ti­mize a bac­te­r­ial meta­bolic process thereby en­hanc­ing bac­te­r­ial fit­ness.
There­fore, the abun­dance of pro­teins in bac­te­ria al­low the bac­te­ria to con­trol when and how cel­lu­lar tasks are ex­e­cuted and to en­sure that each task is per­formed op­ti­mally.
Celia M. Ebrahimi (Stu­dent, In­te­gra­tive Mi­cro­bi­ol­ogy course)