Dr. (I' . I Comment on proposed letter on "Sex Factors and Conjugons" ' h I am willing to sign this letter, or to be counted among the number of aupporters if the journal will not accept a long list of signatures, I do not wish to sponsor this letter but will accept the proposed terminology if the letter is published. I do not approve of the proposal. My apologies for having let this slip. ------------------------------------------------ I certainly approve of "conjugon"; but I think there.will still be semantic problems. "Generate a conjugation apparatus " has a reasonably clear connotation in E. coli K-12; but it is easy to imagine related processes, that will make you wish you had a more precise definition. 'perhaps in other bacteria Does pneumococcus or B. subtilis have a "conjugation apparatus" that we now label as "competence"? Then are you going to distin-guish a block of genes perhaps firmly integrated in a chromosome $ (f plasmid, therefore I assume 4 mrs@n conjugon) from the same DNA sequence outside? fushons So I think to improve the present situation, with all of its con- , you may have to introduce a whole family of terms to cover the various al- ternatives. L k**g:*eThinking out loudf~hk*>kk : defn. of Orthogonal criteria conjugon present Location of particle on/ off chromosome Scope of connected sequence one/few genes // a small chromosome recent history and prospects probable interaction with chromosome or not OFF FEW NOT functions mediated: pilus (penis) that remains attached to source cell and mediates DNA transfer . . . including other genes detachable capsid containing DNA others YES + NO + Potential l'F~m le-speEi6i.c" components are not included in th&s definition of conjugon -- I wonder if it would not be better to use a term that stresses the male-speEi6icity implied here. Would YOU settle for pilosome/ pilogene for the plasmid and its genetic informa- tion respectively, the latter being possibly part of a chromosome. This may not sufficiently excllJCle non-sexu;il I'ili. So maybe rrndxw~alpax androsomelandrogene. Xe; Con;unzr! DC, fb `72 I will be,happy to go along with the term, but I have some comments that would be inconsistent with 'sponsoring' the note in its present text. SUBSTANCE We now know enough to think of several orthogonal criteria and to use these to label a taxonomy of particles. According to a first pass at this (below) one might have a-fairly simple key for the 'species' conjugon. But I predict this will run into new troubles when the concept is cited, used and transformed by others. There tend to be two kinds of difficulty: confusing one species with another; and confusing different hierarchies of the classifica- tion. If I understand you correctly, you would use conjugon only for the extra-chromosomal state of a particle; others more interested in sex and less in plasmids might want to relax this criterion, i.e., to generalize on the definition with respect to one parameter; others with respect to another. And most of our colleagues, being rather impatient with neological and neologistic analysis will use conjugon for whatever happens to certain strains of 6. coli. The minimum prophylaxis is to display the tree explicitly; in addition one mmght wish to provide contrasting names for other nodes -- which one may feel foolish in doing before some of them are experimentally verified (v.i. -- a caution I heeded too well in defining 'plasmid' and leaving what came to be known as 'episome' to a passing reference.) o Orthogonal criteria defn. of conjugon present Location of particle on/ off chromosome Scope of connected sequence one/few genes // a small chromosome recent history and prospects probable interaction with chromosome or not OFF FEW NOT functions mediated: pilus (penis) that remains attached to source cell and mediates DNA transfer . . . including other genes detachable capsid containing DNA others YES + NO + Potential "Female-speEiEic" components are not included in thts definition of conjugon -- I wonder if it would not be better to use a term that stresses the male-spetitiicity implied here. Would you settle for pilosome/ pilogene for the plasmid and its genetic informa- tion respectively, the latter being possibly part of a chromosome. This may not sufficiently exclude non-sexual pili. So maybe xadxsgsa~x androsomelandrogene. HISTORY Perhaps not surprisingly, I have a different perception of the history of these terms than is indicated in the preamble. Certaihly I coined the term PLASMID in 1952 to solve a rather different problem than indicated here-- namely to unify "plasmagenes" and "viruses". X$UIX$J Lysogenicity rather than the F story was the focus of attenttion, as far as bacteria were concerned (the paper was written in 1951 with last minute revisions in early '52 and we-had at most our first glimmers of F at that time). The concept of 'episome' was addressed there in remarks about "a special relationship between the nucleus and some viruses" but until we had completed our first studies of F and of lambda-segregation a few monbhs later, we did not have the datd- a lot of effort trying to persuade various keeping F and lambda unscrambled to spell this out. (We-were spending people that F was not a virion, and Some of the characterizations in that 1952 paper inevitably appear somewhat muddled viewed from hindsight; but I think the definition of plasmid given there can still stand. With the emergence of the episome terminology, people tend to use 'plasmid' to mean an obligately non-chromosomal particle; but there is no easy opera- tional test to help predict whether a particle can ever be integrated. I'm sorry I don't have the reference right to hand; but you may be interested that the term 'episome' had been used earlier by McClintock or by Anderson to refer to particles (like AC in mlize) that migbate from one chromosomal location to another. There is no way to impose a rigorous definition on customary usage. P.S. Checking back in my files, which are intermittently intact, I found only one draft version of the ms, bar that paper-- which has significantly more detailed discussion about lysogenicity. I have to assume that the editors discouraged placing that much emphasis on lambda for a physiological reviews audience, Needless to say, this has no bearing on the public record; except that I have to guard against reading more than actually appears in the prin ed version. Then, I think I have to correct the preamble. The term 'plasmidl, WNI introduced in my 1952 paper without particular reference to F. Its application to temperate phages would also have to be revised in the light of later work-- which justified the general concept ofethe episome as a parti& that alternates between a chromogenic and a plasmagenic habit. PLASMID was coined to unify all extrachromosomal determinants, whether these could also be viewed as 'plasmagenes' or as symbiotic 'viruses', a distinction that I felt to be operapionally meaningless, but which confused many contemporaries. Today, in using *&I&PI term plasmbd (in distinction? to episome)Pasm one must clarify whether one means mxlncrr~~rmmwx existentially extrachromosomal, or obligatorily so. (I know of no way to prove that a plasmid is inherently incaPable of entaring a chromosome, i,e., of functioning as an episome.) I Incidentally episome was coined by McClintock (or Anderson) some years before Jacob for the *atory regulatory factors, like AC in maize. It is no easy task to keep moaninga rtraight -- as Al Hershey used to say, discoveries also keep getting fn the way of simple thinking.