PLASMID
21,
167-174 (1989)
REVIEW
Why Do Bacterial Plasmids Carry Some Genes and Not Others?
WILLIAMG.EBERHARD
Smithsonian Tropical Research Institute and Escuela de Biologia, Universidad de Costa Rica,
Ciudad Universitaria, Costa Rica
Received April 2 I, 1989
Previous explanations of why bacterial genes for certain “optional” traits tend to occur on
plasmids rather than chromosomesare basedon an outdated misunderstandingof natural selection.
They also fail to explain why certain charactersthat are ubiquitous in some bacterial speciestend
to occur on plasmids. This paper shows that all major classesof traits usually associated with
plasmids rather than chromosomes confer adaptations to locally restricted conditions. A new
“local adaptation” model of plasmid evolution, based on simultaneous application of modern
selection theory at the levels of gene, plasmid, cell, and clone reproduction, shows that genes
coding local adaptations will reproduce more successfullywhen on plasmids than when on chromosomes, due to plasmids’ greater horizontal mobility. 0 1989 Academic press, Inc.
Plasmid genes often encode “optional”
characteristics which are selectively advantageous to bacteria in some environments but
not others. The function of plasmids is commonly thought to be to provide a scattered
reserve of variants that enables a population
or speciesto adapt to new environmental contingencies without burdening most individual
cells with often superfluous genes (Reanney,
1976; Hopwood, 1978; Broda, 1979; Koch,
1981; Campbell, 1981; Datta, 1985; Willetts
and Clewell, 1985; Shapiro, 1985). This and
other explanations (e.g., Betley et al., 1986)
that are based on the supposition that natural
selection acts for the good of populations or
speciesare probably wrong.
Advances in evolutionary theory have
shown that the effectsof a trait on lower levels
of reproduction (e.g., individual or genie)
rather than those on higher levels such as populations or species generally determine
whether the trait is favored by natural selection
(Williams, 1966; Dawkins, 1976, 1982; Alexander and Borgia, 1978, Leigh, 1983, 1987;
Ewald and Schubert, in press).This meansthat
because plasmids often have negative effects
on the reproduction of individual bacterial
cells, they cannot be maintained by the occasional benefits they confer on populations
or species.
In addition, some typically plasmid-borne
traits are not optional in the usual senseand
are in fact found in most isolates from nature
(e.g., Brubaker (1985) and Aronson et al.
( 1986) on virulence in enteric bacteria and insect pathogens; Nester and Kosuge ( 1981) on
plant gall bacteria). Somelarge plasmids (>250
MDa) are never absent from Agrobacterium
tumefaciens or the nitrogen-fixing Rhizobium
meliloti, suggesting that the genes they carry
are essential for these cells’ growth (Denarie
et al., 1981). “Optional character” hypotheses
do not account for these traits being on plasmids.
This paper presents an alternative explanation of why genes for some characters but
not others tend to occur on plasmids, using
analysesof differential reproduction of genes,
plasmids, and the cells and clones which contain them. The terms “function” and “adaptation” are used here only in the restricted
senseappropriate for evolutionary discussions:
the function of a trait refers to a context in
which the trait confers reproductive advantage
upon its bearers(vs nonbearers),with the result
that the trait becomes more common in the
population. It is important in evolutionary
discussions,which attempt to distinguish cause
and effect, to differentiate the primary functions of a trait which contributed to its original
167
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All rights of reproduction in any form reserved.
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REVIEW
spread and its maintenance via differences in
the reproduction of bearers and nonbearers,
from second-order effectswhich are incidental
consequences of the trait’s becoming established (Williams, 1966;Gould and Vrba, 1982;
Vermiij, 1987). This distinction between
function and effect has not been made carefully in some previous discussions of the evolution of plasmids and other mobile elements.
To use an example that has generated recent
controversy, when transposons and insertion
sequencespropagate themselves within a genome, they often generate new gene combinations and mutations; these are occasionally
advantageous and have undoubtedly influenced the course of evolution in different
groups. But this does not justify claiming that
the generation of new combinations (which
usually reduce their bearer’s reproduction) is
their function (Campbell, 1981; Syvanen,
1984) (see Charlesworth, 1987). Just because
a consequence of a trait is to increase certain
kinds of change does not mean that the function of the trait is to produce these changes.
general classesof traits tend to be coded on
plasmids rather than chromosomes: “plasmidselfish” characters such as conjugation, mobilization, inhibition of bacterial cell division,
and plasmid surface exclusion and partitioning, which promote the survival and replication of the plasmid as a unit; and optional
characters such as resistance to antibiotics,
heavy metals, and other poisons, virulence,
metabolism of unusual substrates, plant gall
formation, root nodulation and N fixation,
and bacteriocins (Broda, 1979), characters
which favor the survival and reproduction of
the entire cell in certain environments. The
reason plasmid-selfish characterstend to occur
on plasmids is clearly becausethey favor plasmid (rather than chromosome) reproduction;
they make plasmids resembleindependent organisms in some respects(Novick, 1980; Salyers, 1984; Datta, 1985). These traits set the
“rules of the game” for analysesof why other,
non-plasmid-selfish genes also tend to occur
on plasmids.
The question of why optional genestend to
occur on plasmids is posed here at the level of
GENERAL
CONSIDERATIONS
gene reproduction, but its answer involves
Bacterial genesmove between plasmids and analysesat three higher levels of reproduction:
chromosomes (Rowbury, 1977; Hart1 and plasmids vs chromosomes within cells; cells
Dykhuizen, 1984),as well as from one plasmid that do or do not have plasmids in addition
to another (Godwin and Slater, 1979; Broda, to their chromosomes; and clones with or
1979). Given common population sizes and without plasmid-carrying cells. The reproducrates of interchange (e.g., Lewin, 1977), and tive advantages or disadvantages of a given
the probably very long evolutionary lives of gene at these different levels are of course to
many genesin bacteria, it is probable that most some extent synonomous. But some traits can
bacterial geneshave been in both plasmids and increase the reproduction of units at one level
chromosomes repeatedly during their evolu- while decreasing reproduction at others. Hitionary lives. This must be especially true for erarchical living systems show “emergent”
genesassociatedwith insertion sequencesand concerns at different levels (Buss, 1987),aswell
for bacterial specieswith F-like plasmids which as conflicts of reproductive interest between
integrate into the chromosome. Chromosomes different levels (Buss, 1987; seealso Alexander
and plasmids thus share, to a substantial de- and Borgia, 1978; Eberhard, 1980; Cosmides
gree, a common genepool. To determine why and Tooby, 1981; Leigh, 1987). Thus considsome types of genes and not others tend to eration of possible synergisms and conflicts
occur on plasmids, one must ask why some between selection at all four levels is necessary
geneshave done better (made more copies of to understand plasmid evolution. Previous
themselves) when located on plasmids than analyseswhich did not carefully separateand
when on chromosomes.
weigh advantagesat these different levels (e.g.,
Bacterial genesare not randomly distributed Reanney, 1976; Koch, 1981; Campbell, 1981)
between chromosomes and plasmids. Two produced confusing results.
REVIEW
NEGATIVE
EFFECTS
CELL AND CLONE
OF PLASMIDS
REPRODUCTION
ON
Plasmids have been thought to be to some
extent parasitic on the bacteria in which they
reside, reducing the reproductive potential of
their carriers asa result of promoting their own
maintenance and propagation (Salyers, 1984;
Datta, 1985). Most evidence supporting these
ideas is of two types: experimental demonstrations that plasmid-carrying strains usually
lose in competition with similar bacteria when
under more or less artificial conditions (Anderson, 1974; Godwin and Slater, 1979; Melling et al., 1977;Zi.ind and Lebek, 1980;DuvalIflah et al., 1981; Fretter et al., 1983; Scholz
et al., 1985); and demonstration that bacteria
found in natural environments lacking conditions for which plasmid geneswould confer
special advantages(e.g., environments lacking
antibiotics) tend to lose or to lack plasmids
carrying those genes (Grabow et al. (1974),
Koch (1981), and Hughes and Datta (1983)
on antibiotic resistance; Robinson and Tuovinen ( 1984) on heavy metal tolerance; Dowling
and Broughton ( 1986) on root nodulation; see
also Cavalier-Smith (1985) on superfluous
genes in general). The combination of these
lines of evidence suggeststhat plasmids per se
often have negative effectson bacterial fitness.
PLASMIDS
AND LOCAL ADAPTATIONS:
A NEW MODEL
Although rates of horizontal transfer vary
between plasmids and in different bacteria
(Broda, 1979),geneson plasmids are generally
more likely to be transferred horizontally and
thus cohabit cells with different chromosomal
and plasmid genes than those on chromosomes (Wheelis, 1975; Lewin, 1977). The
more frequent horizontal transmission of
plasmid genesresults in a wider variety of genetic settings in which they can act, giving the
plasmid genesmore of the selectiveadvantages
of sexual reproduction (Felsenstein, 1974;
Williams, 1975; Maynard Smith, 1978; Leigh,
1987). One expected result is that plasmid
geneswill be able to evolve more rapidly than
169
chromosomal genes in response to environmental changes.
In addition, genescoding for adaptations to
variations in environmental conditions that
occur only sporadically in time or spaceshould
reproduce more rapidly when on plasmids.
Arguments supporting this claim will be developed using antibiotic resistance as an example, then extended to other functions.
Antibiotics are generally restricted to the
immediate vicinity of antibiotic-producing
organisms such as certain soil fungi, actinomycetes, and other bacteria (Broda, 1979;
Martin and Demain, 1980) and, recently, to
sites of modern medical treatment and industrial antibiotic production. Several factors
contribute to the maintenance of a locally advantageous character like antibiotic resistance
on plasmids rather than chromosomes. Consider two otherwise equal strains of bacteria
carrying an antibiotic resistancegene,one with
the gene on a chromosome and the other with
the gene on a plasmid. The resistance gene
produces a phenotype that has a selective advantage only in the conditions that prevail in
certain locations where antibiotic is present.
At such sites both strains will be favored over
bacteria lacking resistance genes, but the resistance geneson plasmids will outreproduce
those on chromosomes for several reasons:
1. New bacterial strains colonizing the site
are unlikely to carry the resistance gene (e.g.,
Broda, 1979; Koch, 1981; Hughes and Datta,
1983). These new bacteria, which are more
likely to lack a plasmid of the incompatibility
type that carries the resistance gene will thus
be more likely to be receptive to horizontal
transmission and more likely to benefit from
the plasmid-coded local adaptation. Thus advantagesat both the cell and the plasmid levels
would make a resistance gene on a plasmid
able to propagate itself more rapidly than if it
were on a chromosome.
2. The resistancegene on plasmids will inhabit cells containing a much greater variety
of other chromosome and plasmid genomes
than will the geneson chromosomes. Plasmid
geneswill thus have a greater likelihood of as-
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REVIEW
sociating themselves with superior genes for
other functions and winning out in competition between clones. This could be an important advantage if sequential replacements of
clones such as those observed in intestinal
Escherichia coli (Caugant et al., 1981) are
common modes of evolution in bacteria.
3. Some antibiotic resistance genes on
plasmids are amplified quickly when needed
and rapidly eliminated when not needed
(Broda, 1979; Clewell, 1981), conferring increasedfitness on the cells and clones carrying
them. The resistancegene on transposon Tn9
is amplified more readily when the gene is on
a plasmid (fewer other gene products are
needed) than when it is on a chromosome
(Mahajan et al., 1985). This expected advantage will be especially strong when gene
expression is constitutive, as is generally true
for resistance plasmids in gram-negative bacteria (Burman, 1977).
4. There is an additional positive feedback
in the advantages to local adaptation genes
of being on plasmids, since the advantage of
being on a plasmid is greatly increased if the
plasmid already carries another gene or genes
coding for adaptations to the same or similar
local conditions. The tighter the association
between the different conditions for which the
different genes confer advantages, the greater
this additional linkage advantage. Even if the
conditions are very weakly associated, a second gene could benefit from hitchhiking along
with another, at least if the rate of recombination is low enough. When different genes
both confer adaptations to the same conditions, the “piling on” advantage could be very
powerful and probably accounts for the remarkably rapid additions of genesto some resistance plasmids such as the hospital-associated plasmid that added four antibiotic resistance genes and grew from 45 to 65 MDa
in the space of only about 10 years (Datta,
1985), and the mercury resistancetransposon
on the plasmid CS229 in hospitals which also
rapidly added multiple antibiotic resistance
genes(Robinson and Tuovinen, 1984).
of general usefulness (“housekeeping genes”)
to not occur on plasmids (Koch, 1981). Horizontal transmission will not confer the reproductive advantages just mentioned on genes
whose products are useful in all potentially
habitable environments.
COMMON
PLASMID
FUNCTIONS
LOCAL ADAPTATIONS
AS
Some other plasmid functions in addition
to antibiotic resistanceclearly seemto be local
adaptations: the ability to metabolize or otherwise resist heavy metals and other poisons,
which probably usually have patchy distributions (Robinson and Tuovenin, 1984); virulence charactersin facultative pathogens;and
the ability to degrade unusual substrates
(Wheelis, 1975; Broda, 1979; Ghosel et al.,
1985).Some plasmid functions, however, such
as virulence in obligate pathogens, plant gall,
and nodule formation and N fixation, and
production of bacteriocins do not appear to
fit this characterization. I will argue, nevertheless, that they too are only locally adaptive.
I. Virulence Factors
At first glance, virulence (that subset of
characters which is useful in establishing infections by dealing with conditions associated
with the host, but which do not have any
known use to the bacterium in other contexts)
does not seemto be a local adaptation in bacteria which are obligate pathogens. For instance, those bacteria which cause invasive
diseasesin animals generally grow poorly or
not at all outside their hosts (Bulla et al., 1975;
Brubaker, 1985; Aronson et al., 1986), and
virulence factors tend to be present throughout
these bacterial species(Bulla et al., 1975; Brubaker, 1985). Closer examination shows,
however, that these virulence factors probably
confer only local advantages.
Many of these bacteria are not host-specific,
and some attack a wide spectrum of hosts. Different host species appear to harbor disease
bacteria with slightly different virulence-codThe sametype of reasoning explains the re- ing plasmids. For example, there are “literally
verse side of the coin-the tendency for genes thousands of” strains of insecticidal Bacillus
REVIEW
171
invading the host speciesfrom which they were
originally isolated. Different sites on the same
host plant may also require different adaptations, and some Agrobacterium plasmid mutants infect certain sites more effectively than
others (Gheysen et al., 1985). Some plasmids
of both genera even show specificities for certain varieties or cultivars of the host plant species (Nester and Kosuge, 1981; Denarie et al.,
1981).
Plasmids of the less-studied Pseudomonas
savastanoi code a diversity of cytokinins; since
such diversity is associatedwith host specificity
in other groups (seeAronson et al. (1986) on
B. thuringiensis; Cavalieri et al. (1984) on hemolysin plasmids; Panopoulos and Peet( 1985)
on other plant pathogens), this suggeststhat
these plasmids may also may confer host-specific adaptations.
The host specificity of plasmid functions
suggests a locally adaptive selective regime
similar to that just described for virulence factors. Mutualism between clones may also operate, as infections by larger numbers of Rhizobium are more likely to produce nodulation
(Dowling and Broughton, 1986).
In addition, both gall and root nodule bacteria have an alternate habitat (free in the soil
outside of host plants). Different strains differ
in their abilities to survive and compete with
other bacteria in different soil types, and plasmid genes are known to be responsible for
some of these differences (Dowling and
II. Plant Gall and Nodule Factors
Broughton, 1986; see also Moore and CookThe better-studied genera Agrobacterium sey, 1981, on Agrobacterium). In sum, charand Rhizobium are similar to the pathogens acters promoting invasion and intraplant rejust discussed, as host specificity is known to production are clearly adaptations for life in
be encoded on plasmids. The two or three the local vicinity of certain plants.
Agrobacterium species(Elkan, 1981) produce
tumors in 142 genera in 61 families of plants III. Bacteriocins
(Lippincott and Lippincott, 1975), while the
As a group, bacteriocin plasmids are relatwo Rhizobium groups (Elkan, 1981) also grow tively common, at least in some bacteria: 10
in a wide variety of plants (> 1130 speciesin of 32 E. coli isolates collected prior to the anthe families Leguminosae and Ulmaceae) tibiotic era produced bacteriocins, and this
(Stowers, 1985).Not all bacterial strains invade may be an underestimate (Hughes and Datta,
all host speciesequally well, and plasmids of- 1983). If bacteriocin plasmids are so common
ten code this host specificity (Nester and Ko- and are advantageous in competition with
suge, 1981; Moore and Cooksey, 1981; Ghey- other closely related bacteria (Broda, 1979)
sen et al., 1985; Dowling and Broughton, could they still represent only local adapta1986). Strains tend to be particularly good at tions?
thuringiensis and its relatives, and “no single
isolate is active against all pest species” (Aronson et al., 1986); different plasmid-coded protoxins are active againstdifferent insect groups.
Different hemolysin geneson plasmids in vertebrate pathogens also have different levels of
toxicity in different host species(Gaastra and
van Graaf, 1982; Welch and Falkow, 1984;
Goebel et al., 1985). In enterotoxic E. coli that
causediarrhea in man and farm animals, plasmid-coded fimbrial antigens that mediate
adhesion to the intestinal epithelium differ and
are host-specific (Willshaw et al., 1985). These
different virulence factors thus represent adaptations to taxonomically “local” conditions.
Different strains of bacterial pathogens of
plants also often have limited host ranges,and
in some casesit is known that host specificity
is coded on plasmids (Panopoulos and Peet,
1985). It is also possible in both plants and
animals that different individuals of the same
host speciesmay require different adaptations
by pathogens.
A further possible advantage of horizontal
transmission of virulence factors occurs at the
level of mutualisms between clones. Some host
defenses are more likely to be overcome by
massive invasion than by small numbers of
disease organisms (e.g., Hirano and Upper,
1983). Horizontal transmission of virulence
factors could raise the chances of successful
infection for all invading bacteria.
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REVIEW
The probable answer is yes, since most bacteriocins are degraded by proteases such as
those common in important habitats like the
vertebrate intestine and dental plaque (Hardy,
1975). Bacteriocins are also less effective in
anaerobic conditions such as those of vertebrate intestines. These same bacteriocins are
more active in urine, blood, and the peritoneal
cavity (Hardy, 1975). Thus the advantage of
having bacteriocin plasmids probably depends
to a substantial degree on local conditions.
Modulation of bacteriocin production suggeststhat the poisons are costly and only locally useful. When densities of cells containing
baceriocinogenic Co1 factors are increased or
the cells are starved of thymine, the percentage
of cells producing toxin in large quantities rises
from 0.01 to 1% (Broda, 1979). In Erwinia
uredovora bacteriocin production is correlated
with gene amplification, and noninduced
stagesshow only low amplification (Thiry et
al., 1985).
DISCUSSION
The goal of this article is not to explain all
plasmid characters, but to understand why
certain subsets of bacterial genomes-genes
that confer local rather than general adaptations-tend to occur on plasmids rather than
chromosomes. Excluded from consideration
were the large number of cryptic plasmids as
well as other plasmid genes with a variety of
other phenotypic effects (e.g., Koyama and
Yura, 1975; DiJoseph et al., 1973; Chernin
and Mikoyan, 1981). Some plasmid-coded
traits, such as uv resistance in Streptococcus
(Clewell and Gawron-Burke, 1986) may also
prove to be local adaptations. Some cryptic
plasmids may also be found to carry genesfor
local adaptations, while others may be parasitic. Levin and Stewart ( 1980) and Caugant
et al. ( 1981) argue that most cryptic plasmids,
and especially nonconjugative cryptic plasmids, cannot be maintained unless they code
for selectively advantageousfunctions, but this
may not be true for some transposons (Biel
and Hartl, 1983).
The local adaptation theory was presented
above in terms of extreme cases(local vs gen-
era1adaptations), but these are obviously the
ends of a continuum. Genes conferring advantageswhich are lesslocally restricted would
derive lessadvantage from being on plasmids.
And if a given plasmid becamemore and more
common, the disadvantagesto a housekeeping
gene of being on that plasmid would gradually
decrease. Eventual transfer of one or more
such genes could tend to “fix” the plasmid,
making it subject to more chromosome-like
selection, This may have occurred for a large
Rhizobium plasmid (Denarie et al., 1981).
Plasmid-selfish selection is also obviously
important, and some plasmids may simply be
parasites, carrying no genes useful to the cell
(Datta and Hughes, 1983;Salyers, 1984;Datta,
1985). The sheernumbers of plasmids and the
variety of genes they carry suggest that still
other explanations may be needed.
ACKNOWLEDGMENTS
It is a pleasure to thank my colleague and molecular
guru Pedro Leon for patient and thoughtful answers to
many unconventional and naive questions. Discussions
with Allen Herre, Egbert Leigh, Stanley Rand, and Mary
Jane West-Eberhard helped clarify several points. Paul
Ewald, E. G. Leigh, P. Leon, R. Novick, and M. J. WestEberhard made detailed comments on the manuscript. A
conversation with Paul Ewald provided the inspiration for
this project. S.T.R.I. librarians Angel Aguirre and Roberto
Sarmiento helped me obtain references.The Vicerrectoria
de Investigacibn of the Universidad de Costa Rica provided
financial support.
REFERENCES
ALEXANDER,R. D., AND BORGIA,G. (1978). Group selection, altruism, and the levels of organization of life.
Annu. Rev. Ecol. Syst. 9, 449-474.
ANDERSON,J. D. (1974). The effect of R factor carriage
on the survival of Escherischia coli in the human intestine. J. Med. Microbial. 7, 85-90.
ARONSON,A. I., BECKMAN,W., AND DUNN, P. (1986).
Bacillus thuringiensis and related insect pathogens.Microbiol. Rev. 50, l-24.
BETLEY, M. J., MILLER, V. L., AND MEKALANOS,J. J.
(1986). Genetics of bacterial endotoxins. Annu. Rev.
Microbial. 40, 577-605.
BIEL, S. W., AND HARTL, D. L. (1983). Evolution of transposons: natural selection for Tn5 in Escherischiu
coliKl2. Genetics 103, 581-592.
BRODA,P. (1979). “Plasmids.” Freeman, San Francisco.
BRUBAKER,R. R. (1985). Mechanisms of bacterial virulence. Annu. Rev. Microbial. 39, 2 l-50.
BULLA, L. A., RHODES,R. A., ANDJULIAN,G. ST. (1975).
REVIEW
Bacteria as insect pathogens.Annu. Rev. Microbial. 29,
163-190.
BURMAN,L. G. ( 1977).Expressionof R. plasmid functions
during anaerobic of an Escherichia coli K-12 host. J.
Bacterial. 131, 69-75.
Buss, L. (1987). “The Evolution of Individuality.”
Princeton Univ. Press,Princeton, NJ.
CAMPBELL,A. (198 1). Evolutionary significance of accessary DNA elements in bacteria. Annu. Rev. Microbial.
35,55-83.
CAUGANT,D. A., LEVIN, B. R., AND SELANDER,R. K.
(198 1). Genetic diversity and temporal variation in the
E. coli populations of a human host. Genetics98,467490.
CAVALIER-SMITH,T. (1985). Introduction: The evolutionary significance of genome size. In “The Evolution
of Genome Size” (T. Cavalier-Smith, Ed.), pp. l-36.
Wiley, New York.
CAVALIERI,S. J., BOHACH,G., AND SNYDER,I. S. (1984).
Escherichia coli hemolysin: Characteristicsand probable
role in pathogenicity. Microbial. Rev. 48, 326-343.
CHARLESWORTH,
B. (1987). The population biology of
transposable elements. Trends. Ecol. Evol. 2, 2 l-23.
CHERNIN,L. S., AND MIKOYAN, V. S. (1981). Effects of
plasmids on chromosome metabolism in bacteria. Plasmid 6, 119-140.
CLEWELL,D. B. (1981). Plasmids, drug resistance, and
genetransfer in the genusStreptococcus.Microbial. Rev.
45,409-436.
CLEWELL,D. B., AND GAWRON-BURKE,C. (1986). Conjugative transposonsand the dissemination of antibiotic
resistance in streptococci. Annu. Rev. Microbial. 40,
635-659.
COSMIDES,L. M., AND TOOBY, J. (1981). Cytoplasmic
inheritance and intragenomic conflict. J. Theor. Biol.
89,83-129.
DATTA, N. (1985). Plasmids as organisms. In “Plasmids
in Bacteria” (D. Helinski, S. Cohen, D. Clewell, D.
Jackson, and A. Hollaender, Eds.), pp. 3-16. Plenum,
New York.
DATTA, N., AND HUGHES,V. M. (1983). Plasmids of the
same Inc groups in Enterobacteria before and after the
medical use of antibiotics. Nature 306, 6 16-6 17.
DAWKINS,R. (1976). “The Selfish Gene.” Oxford Univ.
Press,Oxford.
DAWKINS,R. (1982). “The Extended Phenotype.” Oxford
Univ. Press,San Francisco.
DENARIE, J., BOISTARD,P., AND CASSE-DELBART,F.
(1981). Indigenous plasmids of Rhizobium. Int. Rev.
Cytol. Suppl. 13, 225-246.
DIJOSEPH,C. G., BAYER, M. E., AND KAJI, A. (1973).
Host cell growth in the presenceof the thennosensitive
drug resistancefactor, Rtsl. J. Bacterial. 115, 399-4 10.
DOWLING,D. N., AND BROUGHTON,W. J. (1986). Competition for nodulation of legumes. Annu. Rev, Microbiol. 40, 131-157.
DUVAL-IFLAH, Y., RAIBAUD, P., AND ROUSSEAU,M.
(198 1). Antagonisms among isogenic strains of Escherichia coli in the digestive tracts of gnotobiotic mice.
Infect. Immun. 34, 957-969.
173
EBERHARD,W. G. (I 980). Evolutionary consequencesof
intracellular organelle competition. Q. Rev. Biol. 55,
23 l-249.
ELKAN, G. H. ( 198I). The taxonomy of the Rhizobiaceae.
Int. Rev. Cytol. Suppl. 13, 1-14.
EWALD, P. W., AND SCHUBERT(in press). Vertical and
vectorbome transmission of insect endocytobionts, and
the evolution on benignness. In “CRC Handbook of
Insect Endocytobiosis: Morphology, Physiology, Genetics and Evolution” (W. Schemmler, Ed.). CRC Press,
Boca Raton, FL.
FELSENSTEIN,
J. (1974). The evolutionary advantage of
recombination. Genetics 78, 737-756.
FRETTER,R., FRETER,R., AND BRICKNER,H. (1983).
Experimental and mathematical models of Escherichia
coli plasmid transfer in vitro and in vivo. Infect. Immun.
39,60-84.
GAASTRA,W., AND VAN GRAAF,F. K. (1982). Host-specific fimbrial adhesins of noninvasive enterotoxigenic
Escherischia coli strains. Microbial. Rev. 46, 129- I6 1.
GHEYSEN,G., DHAESE,P., VAN MONTAGU, M., AND
SCHELL,J. (1985). DNA flux across genetic barriers:
The crown gall phenomenon. In “Genetic Flux in
Plants” (B. Hohn and E. S. Dennis, Eds.), pp. 1l-47.
Springer-Verlag. New York.
GHOSAL,D., You, I.-S., CHATTERJEE,D. K., AND CHAKRABARTY,A. M. (1985). Plasmids in the degradation
of chlorinated aromatic compounds. In “Plasmids in
Bacteria” (D. Helinski, S. Cohen, D. Clewell, D. Jackson,
and A. Hollaender, Eds.), pp. 667-686. Plenum, New
York.
GODWIN,D., AND SLATER,J. H. (1979). The influence of
growth environment on the stability ofa drug resistance
plasmid in Escherischia coli K12. J. Gen. Microbial.
111,201-210.
GOEBEL,W., HACKER,J., KNAPP,S., THEN, I., WAGNER,
W., HUGHES,C., AND JUAREZ,A. (1985). Structure,
function, and regulation of the plasmid-encoded hemolysin determinant of Escherichia coli. In “Plasmid
in Bacteria” (D. Helinski, S. Cohen, D. Clewell, D.
Jackson, and A. Hollaender, Eds.), pp. 791-806.
Plenum, New York.
GOULD, S. J., AND VRBA, E. SS. (1982). Exaptation-A
missing term in the scienceof form. Paleobiology 8,415.
GRABOW,W. 0. K., PRIZESKY,0. W., AND SMITH,C. S.
(1974). Review: Drug resistant coliforms call for review
of water quality standards. Water Res. 8, 1-9.
HARDY, K. G. (1975). Colicinogeny and related phenomena. Bacterial. Rev. 39,464-5 15.
HARTL, D. W., AND DYKHUIZEN,D. E. (1984). The population genetics of Escherischia oli. Annu. Rev. Genet.
18,31-68.
HIRANO, S. S., AND UPPER,C. D. (1983). Ecology and
epidemiology of foliar bacterial plant pathogens.Annu.
Rev. Phytopathol. 21, 243-269.
HOPWOOD,D. A. (1978).Extrachromosomally determined
antibiotic production. Annu. Rev. Microbial. 32, 37392.
HUGHES,V. M., AND DATTA, N. (1983). Conjugative
174
REVIEW
plasmids in bacteria of the “pre-antibiotic” era. Nature
(London) 302,725-726.
KOCH,A. L. (1981).Evolution of antibiotic resistancegene
function. Microbial. Rev. 45, 355-378.
KOYAMA,A. H., ANDYURA, T. (1975).Plasmid mutations
affecting self-maintenance and host growth in E&erichia coli. J. Bacterial. 122, 80-88.
LEIGH, E. G. (1983). When does the good of the group
override the advantage of the individual? Proc. Natl.
Acad. Sci. USA 80,2985-2989.
LEIGH, E. G. (1987). Ronald Fisher and the development
of evolutionary theory. II. Influences in new variation
on evolutionary process.Oxford Monogr. in Evol. Biol.
LEVIN,B. R., ANDSTEWART,F. M. (1980).The population
biology of bacterial plasmids: A priori conditions for the
existence of mobilizable nonconjugative factors. Genetics 94,425-443.
LEWIN, B. (1977). Gene expression. In “Plasmids and
Phages,” Vol. 3, pp. l-925. Wiley, New York.
LIPPINCO~T,J. A., AND LIPPINCOTT,B. B. (1975). The
genusAgrobactrium and plant tumorigenesis.Annu. Rev.
Microbial. 29, 377-406.
MAHAJAN, S. K., PANDIT, N. N., AND SARKARI, J. S.
(1985). Genetics of amplification of transposon Tn9 in
Escherichiu co/i. In “Plasmids in Bacteria” (D. Helinski,
S. Cohen, D. Clewell, D. Jackson, and A. Hollaender,
Eds.), p. 895. Plenum, New York.
MARTIN, J. F., AND DEMAIN, A. L. (1980). Control of
antibiotics synthesis.Microbial. Rev. 44, 230-25 1.
MAYNARD SMITH, J. (1978). “The Evolution of Sex.”
Cambridge Univ. Press,Cambridge.
MELLING,J., ELLWOOD,D. C., AND ROBINSON,A. (1977).
Survival of R factor carrying Escherischia coli in mixed
cultures in a chemostat. FEMS Microbial. Lett. 2, 87-
ROWBLJRY,R. (1977). Bacterial plasmids with particular
reference to their replication and transfer properties.
Prog. Biophys. Mol. Biol. 31, 21 l-3 17.
SALYERS,A. A. (1984). Bacteroides of the human lower
intestinal tract. Annu. Rev. Microbial 38, 293-3 13.
SCHOLZ,P., HARING, V., SCHERZINGER,
E., LURZ, R.,
BAGDASARIAN,
M., SCHUSTER,
H., AND BAGDASARIAN,
M. (1985). Replication determinants of the broad host
range plasmid RSFlOlO. In “Plasmids in Bacteria” (D.
Helinski, S. Cohen, D. Clewell, D. Jackson, and A. Hollaender, Eds.), pp. 243-260. Plenum, New York.
SHAPIRO,J. A. (1985). Mechanismsof DNA reorganization
in bacteria. ht. Rev. Cytol. 93, 25-56.
STOWERS,
M. D. (1985).Carbon metabolism in Rhizobium
spp. Annu. Rev. Microbial. 39,89- 108.
SYVANEN,M. (1984). The evolutionary implications of
mobile genetics elements. Annu. Rev. Genef. 18, 271293.
THIRY, G., THIRY, M., THIRY-BRAIPSON,
J., FAELEN,M.,
MERGEAY,M., AND LEDOUX, L. (1985). Functions of
extrachromosomal DNA in the epiphytic bacterium
Erwinia uredonora. In “Plasmids in Bacteria” (D. Helinski, S. Cohen, D. Clewell, D. Jackson, and A. Hollaender, Eds.), p. 911. Plenum, New York.
VERMIIJ,G. (1987). “Evolution and Escalation.” Princeton
Univ. Press,Princeton, NJ.
WELCH,R. A., AND FALKOW,S. (1984). Characterization
of Escherichia coli hemolysins conferring quantitative
differences in virulence. Infect. Immun. 43, 156-160.
WHEELIS,M. L. (1975). The geneticsof dissimilarity pathways in Pseudomonas.Annu. Rev. Microbial. 29, 505524.
WILLETTS,N., AND CLEWELL,D. (1985). Chairmen’s introduction: Plasmid transfer. In “Plasmids in Bacteria”
89.
(D. Helinski, S. Cohen, D. Clewell, D. Jackson, and A.
MOORE,L. W., AND COOKSEY,D. A. (198 I). Biology of
Hollaender, Eds.), pp. 43 l-432. Plenum, New York.
Agrobacterium tumescens:Plant interactions. Int. Rev.
Cytol. Suppl. 13, 15-46.
WILLIAMS,G. C. (1966). “Natural Selection and AdapNESTER,E. W., AND KOSUGE,T. (198 1). Plasmids spectation.” Princeton Univ. Press,Princeton, NJ.
ifying plant hyperplasirs.Annu. Rev. Microbial. 35,53 I- WILLIAMS, G. C. (1975). “Sex and Evolution,” pp. l-200.
565.
Princeton Univ. Press,Princeton, NJ.
NOVICK, R. (1980). Plasmids. Sci. Amer. 243(6), 76-90.
WILLSHAW,G. A., SMITH, H. R., MCCONNELL,M., AND
PANOPOULOS,
N. J., AND R. C. PEET.(1985). The molecROWE,B. (1985). Expression of cloned plasmid regions
ular geneticsof plant pathogenic bacteria and their plasencoding colonization factor antigen I (CFA/I) in Eschmids. Annu. Rev. Phytopathol. 23, 38 I-419.
erichia coli. Plasmid 13,8- 16.
REANNEY, D. (1976). Extrachromosomal elements as ZOND, P., AND LEBEK, G. (1980). Generation time-propossible agents of adaptation and development. Baclonging R plasmids: Correlation between increases in
teriol. Rev. 40, 552-590.
the generation time of Escherichia co/i caused by R
ROBINSON, J. B., AND TUOVINEN, 0. H. (1984). Mechaplasmids and their molecular size. Plusmid 3, 65-69.
nisms of microbial resistanceand detoxification of mercury and organomercury compounds: Physiological,
biochemical, and genetic analyses.Microbial. Rev. 48,
Communicated by Richard P. Novick
95- 124.