Evolution of plague virulence

Reprinted from Nature, Vol. 334, No. 6182, pp. 473-474,
@ Macmillan Magazines
11 August 1988
Ltd,. 1988
pressures that were responsihle for the
incrcase in the frequency of hypervirulent
strains. once they appeared hy mutation.
Indeed. for many years. conventional
wisdom favoured the view that evolution
Richard E. Lenski
would select those pathogens which had
the least harmful effects on their hosts'.
WHAT was the ancestral form of the consistent with its much greater virulence
On the other hand. pathogenicity. or virurelative to Y. pseudotuberculosis and with lence. is often associated with transmishuman immunodeficiency virus (HIV)?'
How did HIV become so virulent? We its inability to grow invasively in sion". Mathematical analyses hy May and
Anderson'" and hy Levin and Pimentel"'"
do not yet know the answers to these mammalian cell cultures.
Wolf-Watz and colleagues have shown have shown that the evolution of pathoquestions, but on page 522 of this issue',
Rosqvist, Skurnik and Wolf-Watz present
previously
that
virulence
plasm ids gens is highly dependent on this coupling
pYV019 and pIB 1, carried by Y. pestis and between transmissihility and virulence.
an interesting hypothesis for the genetic
basis of the evolution of virulence in a by Y. pseudotuberculosis, respectively,
To see this. consider a simple equation
for the rate of change in the numher of
former scourge, the bubonic plague. They have a high degree of homology.. Both
hypothesize that less virulent strains of carry the yopA gene, although only Y. infected hosts in a population: dYldt =
Yersinia pestis, the bacterium that causes pseudotuberculosis expresses the corres- f3XY - aY. where X is the numher of
bubonic plague, were harboured by non- ponding Yopl protein'. In the work susceptible hosts. Y the numher of infechuman hosts, rats and fleas, during en- reported in this issue, Rosqvist et al. have ted hosts, f3is the transmission rate of the
demic phases. Single point mutations could sequenced the yopA genes from Y. pestis pathogen and a the rate of mortality inand Y. pseudotuberculosis and find only cluding that induced hy the pathogen. If
have given rise to hypervirulent strains,
..,. the number of susceptihles IS very high.
:c
the rate of increase of the pathogen - as
~
0( reflected by the rate of increase of infected
t
hosts - will generally he maximized when
0 the transmission rate is high. even if this
I]
0 entails a high rate of host mortality. In
..J
contrast. reduced virulence could he
E
" favoured if perpetuation of the pathogen
"
I' ::E
depends on prolonged survival of infected
"c
;! carriers. as may occur when the numher of
II .;; surviving susceptible hosts is vcry low. In a
sense, a critical factor from the perspective of the pathogen is whether there is
ample opportunity for infectious exploitation of other hosts or whethcr heing 'nice'
to a current host is the hest way of achieving maximal fitness".
The dramatic declines of the human
population in Europe during the great
plague epidemics of past centuries were
presumably accompanied by comparable
declines in the population of susceptible
rodents. Not only might these epidemics
have been triggered by the appearance of
St Gregory's procession against the plague. From the Soane Book of Hours, ca 1500.
which spread to cause the plague epidemics.
15 nucleotide differences among 1,230 hypervirulent strains of Y. pestis, as
Rosqvist. Skurnik and Wolf-Watz hypoRosqvist et al. base their hypothesis on base pairs. One of these differences,
their elucidation of the genetic determinahowever, is a one-base deletion that thesize'. but the declining populations of
susceptible hosts may in turn have
tion of virulence in Y. pseudotuberculosis,
throws off the reading-frame in Y. pestis.
which is closely related to Y. pestis. The
The non-functional yopA gene in Y. favoured less virulent strains.
In a similar way. mortality among
two are essentially indistinguishable from pestis is presumably derived from a funcDNA hybridization data' and Y. pseudotional ancestral state. When Rosqvist groups at high risk for AIDS. together
tuberculosis infections in rats provoke
et al.' introduce the functional gene from with changing patterns of behaviour. may
immunity to Y. pestis. Previous work has Y. pseudotuberculosis into Y. pestis, they radically alter selection acting on the
implicated two outer-membrane proteins
observe a corresponding reduction in the human immunodeficiency virus (HIV).
in mediating the invasion of mammal,ian virulence of Y. pestis. Thus, Y. pestis has How that might effect the evolution of the
cell cultures by Y. pseudotuberculosis:
apparently undergone a mutation in the virus is not clear. owing to our present
invasin, which is encoded chromosomally',
past that caused loss of function of the ignorance. As May and Anderson" have
and Yopl, which is encoded by a plasmid'.
yopA gene, with a concomitant increase in emphasized. we do not even know if
heterosexual transmission of HIV is selfRosqvist et al. demonstrate that mutations
its virulence. This supports the hypothesis
sustaining in developed countries.
0
in one or the other of the genes encoding
that single mutations played an important
these proteins have little effect on virulence role in triggering plague epidemics'.
I. Smith.TF etal. Nalllre333.5B-575(I~KK).
:!. Rosq,..ist. R.. Skurnik. M & \\'olf-\\'atl. H. J\alllfe 334.
of Y. pseudotuberculosis in mice. But when
But mutations alone cannot drive epi522-525 (I~KK).
mice were administered bacteria containdemics. The necessary genetic variability
3. Rcrcovier. II. ('( al. ('11". Miaohiol. 4. 225-229 (19HO).
4. Ishcrg. R. R. & F3lkow. S. Nt/lllre 317.262-264 (I~K5).
ing mutations in both genes, that is, lnvin the pathogen must exist and so must
5. Bolin. I.. Norlander. L. & Wolf-Walz. H./nfl'cl./mmuni(\
and Yopr, the LD~, went down dramatithe appropriate selective conditions for
37.5116--512(I~R2).
6. Porlnoy. D.A. fit/I. Infect. Immw,;n' 43. 1OX-114(I~K4).
cally, indicating a heightened degree of the spread of hypervirulent mutants.
7. Bolin. L rIal. Infecl. Immwlit.\' 56. 3.B-3~X (IIJAA)
virulence. Y. pestis apparently expresses
Hence, there remains the equally perR. May. R.M. & Anderson. R.M. in Conol",icm (ed~
neither invasin nor the Yopl protein,
plexing question concerning the selective
Futuyma. DJ. & Sialkin. M.) IN6-20fl (Sinaucr Associ-
Epidemics
Evolution of plague virulence
T
I
--
ates. Sundl'rland. Massachusetts. 19N3)
-
9. Anderson. R.M. & May. R.M. Parasilology85.411 (1982).
10. Levin. S.A. & Pimentel. D. Am. Nor. 117.308-315 (1981).
11. Levin. S.A. in Coevolw;on (ed. Nitecki. M.H.) 21--65
(Univ. Chicago Press. 1983).
12. Levin. B.R. & Lenski. R.E. in Conolution (cds Futuvma.
DJ. & Slatkin. M.) 99-127 (Sinauer Associates. Su~der.
land. Massachusetts. 1(83).
13. May. R.M. & Anderson. R.M. Nawre326.137.142(1987).
Richard E. Lenski is in the Department of
Ecology and Evolutionary Biology, University
of California, Irvine, California 92717, USA.
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