Experiment Station Project No. Th?
Bacterial genetics. Reckefeller Yount.,
Mat") Inet. wealth, & W.A.R.F. Suppert.

Gonptien of Becterta

Ferscuml: Dr, J. Lederberg
Br, B. Ma. Lederberg
Dr. M. L, Mores

Dr. S$. 6, Bradley (RSF fellow)

Assistants: D, C, Gosting; HM. L.
R, E, Weights T. Timez A. eer

Support: Ils Rockefeller; W.A.2.F.
—_— |
JAN 6 1956
fw Pic ~ Bacterial Geneties=-Research Report for 1955

Submitted by J. Lederberg, Professor of Genetics,

t " / oi -L Universi ty of Wisconsin, Madison, Wisconsin

The work in this laboratory continues to center on ths genetic recombina-
tional mechanisms of bacteria: sexuality, transduction, and virus infection. —
This past year hag seen no remarkable new advances, and has been devoted mainly
to clarifying minor discrepancies, and consolidating earlier advances.

1. A considerable amount of time was spent to try te reach a definite con»
clusion concerning the residual unit which is propagated, without multiplying,
in succeeding csll divisions cf some Salmonella cells after "abortive" or
"phenotypic® transduction (5,18). The main conclusion is that no definite de«
cision could be made whether the unit is particulate, and if so whether it repre-
sents a partly inactivated "gene", or simply a gene product. Other workers hove
sought to make more conclusive inferences from the same kind of data,

2, Additional work on conjugal pairs of E, coli has corroborated esrlicr
indications of their sienificance in the sexual cycle of this bacterium, so that
a preliminary account is now justified (9). However, no further progress has
been made in tracing the morphogenetic details of sexual conjugation by micro-
scopic methods.

3. Further study of the relationship between a provirus and other genes of
E. coli (7,8,16) substantiates the hypothesis that a virus is equivalent to a
segment of the bacterial chromosome and that the lysogesnization for a virus
corresponds to a special transduction, Some aspects of this relationship are
still obscure and require further study.

hh. Ag an important tool for the preceding studies, considerable effort has
been devoted to the development of properly marked divioid stocks of F. coll
(normally haploid) which can be used more informatively for routine crossing
purposes. This has proved to be more laborious than had been anticipated, and

is not yet completed, but should repay the effort in due courss,
5, Some second-order discrepancies of observation (3) hawe been clarified
by the finding that different stecks of the Hfr mating type of E. coli show dif»
ferent segregational behevier, ‘The genetic basis and orlsin of these differences
ave being studied now, and are tha most promising leads to clearing up some of
the remarkable peculiarities of the genetics of this organism, as quoted in pre-
vious reports and elsewhere (1).

6, Ag a reneval of some preliminary experiments in 1951-52, a siady has been
made of Streptomyces species to determine whethor a system of genetic recombinase
tion covld be detected (17). This study was motiveted by the interesting taxonomic
and morphogenetic status of these "bacteria", on the one hand, and on the other
by their economic importance in the fermentation industries as sources of antie
biotics and feed supplements, which bas led in turn to their close physiological
study by other workers. However, almost no genetic work had been done with those
organisms until recently. A mumber of species have been examined, including 5.
griseus, by the same basic technique formerly employed with other bacteria, the
combination of different mitritional mutants. No definite evidence for genic
recombination has been found, However, it has been verified that hyphae of dif»
ferent strains will fuse, to allow the intermixture of different moclei in 2
common cytoplasm, namcly heterckaryosis, These muelei are capable of interacting
to produce new physiological effects, This system, while it may be of some in»
dustrial application in the development of suitable strains, is far less ad=
vantageous than true genic recombination for the prospects of controlled breoding,.
While this work was proceeding, a fragmentary report appeared on the occurrence
of recombination in another apscies, 5. coelicolor. This work complements ours
in many respects; it also raises the question of why the strains should behave
differently, perhaps because of sexual compatibility factors which can now be

investigated.
7. Provicus reports have outlined the fects of flagellar "phase varlation"

tue almost

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in Salmonella, Briefly, clones of this organism can persist

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siable states, accordin: two notential entigens are actually pro-

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dueed. The two antigens are contrelied by two different genes: we may ask the
question: What controls which of two genic potentialities is actually realized? <=
a question analogous to those posed by differentiation of tissue cells, but one
uhich is nov often encountered in genetically analysable material, Transduction
analysis has now shown that one of the two genes exists in either of tuo states:
an "active" state which promotes its own realization, and suppresses that of

the other, and, conversely an "inactive" state. In technical terminology, we
may refer to these states as “epistatic" and “hypostatic", respectively, While
the differentiation has thus been localized at the actual site of one of the
jnvelved genes (and not, for exemple, in the cytoplasm or at the second gone)

we still de not lmow its wltimate chemical or physiological basis, This nar
rowing may, however, lead to further advances in this direction, It is perhaps
significant that during the very course of these studies, the interest of
morphogeneticists hes been turned again to the nucleus, and away from the cyto~
plasm, as the seat of differentiation by such studies as the mecleer trans=
plantations (in frogs, not bacteria) of Briggs and King.

8, As a remerkable example of "pleiotropy", or manifold physiological ef-
feets of a single pene mutation, it has been found that the same mutation which
inhibits maltose fermentation alse makes the bacteria resistant to a virus,
lambda«-? (6). There is no perceptible causal relationship between these

phenotypes.
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1955 Publications

ederbarg, Je 1955. Recombination mec hanisas in bacteria, Jour. Cell, Comp.

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Physic, 45, Suppl. 2, 75-107 (lay),

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Ledexvberg, J, 1955, Genetics and microblolosy. in Perspectives and
in Microbiolocy (S, A. Wakeman, Ed,) Rutgers Univ. Press.

Lederberg, J. 1955, Genetic recombination in bacteria, Seience 1222920,
(November).

Bernstein, A. and Lederberg, d. 1955, Agglutinaticn cf motile Salmonelles
by acridines, Jour. Bact. 69:1),2-146,

Lederberg, J, and Stocker, B.A.D.5, 1955. "Phenotypic" transductdons of
motility in Salmonella, Geneties 10:581. (abstr.)

Lederberg, E. Me 1955, Pleiotropy for maltese fermentation and phage vosis~
tances in Escherichia coli K-12. Genoties h02580-581, (abstr.)

Moree, M. Us 1955, Gisstrans position effect in transduction heterocenotes

of Escherichia coli, Geneties 1:0:586-537, (abstr.)

In Press (1956)

Morse, M. i, Lederbarg, E. HM. and Lederberg, J, 1956, Transductioa in
Escherichia coli K-12, Genebies h1:12-1)5,

Lederberg, J. 1956. Conjugal pairing in Becherichia coli, dour, Bact, Ti.

Lederberg, Je 1956, Prospects fer the genetics of tumor and cancer cells.
Amn. N. Y, Acad. Sei.

Lederberg, 3. 1956, Coumentary on gene-enzyre relationships, International
Symposium cn Enzymes, Henry “ord Hosp., Detroit, Michican,

Lederberg, J. 1956. Genetic transduction. (acceptance perding).

Nelson, 7. C. 1956, Sexual competence in Escherichia coli. -Jour. Cell, Coan.

Physiole
156

16.

17.
18.

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Cevalli, L. L. and Lederberg, J. 1956. Isolation of preadaptive mutants of
bacteria by sib-clene selection, Genetics hl,

Lederberg, J, and Lederbsrg, BE. M. 1956. Infection and Heredity. Symp. Sec,

Growth and Development,

Almost ready for Submission

Morse, HM. L., Lederberg, J. and Lederberg, E. M, Transduction heterogenotes
in Escherichia coli.

Bradley, S. G. and Lederberg, J. Heterokaryosiz in Streptomyces,

Lederberg, J, Hereditary chains of descent in Salmonella, (tentative title).

Lederberg, J, and Iino, T. A duplication of antigen-determining loci in
Saimonella,