Fine Read­ing: A Brief His­tory of Plas­mids

by Roberto

That plas­mids are au­tonomous rep­licat­ing ele­ments and that they can serve as excel­lent clon­ing vec­tors are facts most cer­tainly well-known to STC read­ers. How­ever, I ven­ture to guess that the same can­not be said about the his­tor­ical de­tails of the when, how, and why plas­mids be­came the sub­ject of in­tense study and the many impor­tant contri­butions that those stud­ies pro­vided to bi­ol­ogy. That is one rea­son why I am strongly recom­mend­ing a re­cent re­view, A Brief His­tory of Plas­mids, by Don He­lin­ski and pub­lished in ASM's EcoSal Plus. (Many thanks to Christoph for point­ing Don's re­view out to me.)

Fig. 1. Elec­tron mi­cro­graph of a replic­ative inter­med­iate of the plas­mid ColE1, af­ter nick­ing with DNAse I. Source

A sec­ond rea­son is much more per­sonal. In the early 1970s, while I was an under­grad­uate work­ing on DNA poly­mer­ase I, I be­came fascin­ated with plas­mids. I saw them as ideal sys­tems for study­ing the regul­ation of DNA replic­ation. So, it was no sur­prise that when I started in the Ph.D. prog­ram at UCSD, I joined Don's lab to do my the­sis. As the tools of recom­binant DNA be­came avail­able, we ex­ploited them to de­fine the ba­sic work­ing parts of plas­mids, aim­ing to test the "repli­con hy­pothe­sis" elabor­ated in the land­mark 1963 pa­per of Ja­cob, Bren­ner and Cuzin. The lab's ex­treme excite­ment sur­round­ing the rapid prog­ress we made re­mains firmly planted in my mind. Read­ing Don's retell­ing of the events of those times al­lowed me to re­live that excite­ment. In his words: "The ad­vent of in vitro recom­binant DNA tech­nology in the early 1970s gave rise in the follow­ing years to a burst of infor­mation on plas­mid DNA struc­ture, includ­ing defin­ing the essen­tial ele­ments for the initia­tion of repli­cation and the cir­cuitry for the con­trol of plas­mid copy num­ber..." "...restric­tion endo­nucle­ase analy­sis of plas­mids dem­on­strated that, in many but not all cases, the replic­ation initia­tion pro­tein could act in trans on a replic­ation ori­gin, allow­ing for the separ­ation of the ori­gin from the initia­tion gene and the mainten­ance of the coval­ently closed form of the ori­gin frag­ment in a bacter­ium that also har­bored a com­patible plas­mid carry­ing the initia­tion pro­tein gene." Mil­lion thanks for writ­ing this won­derful es­say, Don!