, et al.Sergey
Kryazhimskiy In Evolution, the Sum Is
Less than Its PartsDOI:
10.1126/science.1208072 , 1160
(2011);332 Science
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(print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in
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of Science; all rights reserved. The title
Laboratory experiments with bacteria
shed light on how epistatic
interactions infl uence the pace of
evolution.
PERSPECTIVES
E V O L
U T I
O N
In Evolution, the Sum Is
Less than Its Parts
Sergey Kryazhimskiy , 1, 2 Jeremy A. Draghi , 1 Joshua B. Plotkin
1
Ancestor strain Adapted strainEvolves in lab
Fitness Wab
P
ropagati
ng bacteria
in a lab for
thousands of
generations
may seem
tedious, or
even irrelevant, to
most evolutionary
biologists.
Nonetheless, such
experiments provide
an opportunity to
deduce quantitative
principles of evolution
and directly test them
in controlled
environments.
Combined with
modern sequencing
technologies, as well
as theory, recent
microbial experiments
have suggested a
critical role for genetic
interactions among
mutations, called
epistasis, in
determining the pace
of evolution. Two
papers in this issue,
by Khan et al. on
page 1193 ( 1) and
Chou et al. ( 2) on
page 1190, present
precise experimental
measurements of
these epistatic
interactions.
< W• W
b
ab
a
Fitness
Wb
D
i
minishing
returns
2
n
3rd mutation
d
1
s
t
m
u
t
a
t
i
o
n
F
Reconstruct
i
intermediates
Antagonistic
epistasis W
tness Wa
m
u
t
a
t
i
o
n
Antagonistic epistasis. Bacteria adapt to a laboratory environment by acquiring bene fi cial mutations. Khan et al. and Chou
et al. identifi ed the mutations that accrued in an adapted strain, and measured their fi tness benefi ts (growth advantage
relative to the ancestor). The mutations conferred smaller marginal bene fi ts in combination than they did individually. This
antagonistic epistasis causes progressively slower rates of adaptation over time.
CREDIT: ADAPTED BY P. HUEY/S CIENCE
Fitness
on June 2, 2011www.sciencemag.orgDownloaded from
Microbial evolution experiments in a late predictive evolutionary models or to tions, individually and in combination, the
simple, constant environment reveal a infer such interactions from empirical data. researchers were able to directly quantify the
characteristic pattern: At fi rst, a
Nevertheless, epistasis is at the heart of extent and form of epistasis (see the fi gure).
population rapidly acquires beneficial classical theories, such as the evolution of
Both studies found a predominance
sex ( 8), and also of modern concepts suchof antagonistic epistasis, which
mutations, but then adaptation
progressively slows so that thousands as robustness and evolvability (a
impeded the rate of ongoing
population’s ability to evolve) ( 9).
of generations pass between
adaptation relative to a null model of
subsequent benefi cial substitutions ( Moreover, recent theoretical work ( 10)
independent mutational effects. Chou
3). Unexpected outcomes, however, suggests that the overall dynamical pattern et al. further interpreted the
can and do occur even in these simple of adaptation observed in longterm
prevalence of antagonistic epistasis in
experimental conditions. Populations microbial experiments can be explained by terms of metabolic costs and benefi ts.
evolve a dramatically elevated
a prevalence of what is called antagonistic The concordance of results from the
mutation rate ( 4), discover rare
epistasis, in which benefi cial mutations
two studies is noteworthy, especially
phenotypic innovations ( 5), or diverge confer less benefi t in combination than
because Khan et al. analyzed
into distinct lineages that either coexist they do individually.
Escherichia coli populations [from the
( 6) or compete vigorously as each
long-term experiments of Lenski ( 3)],
strain races to acquire more adaptive
whereas Chou et al. studied an
mutations ( 7). Recent theory suggests
engineered strain of Methylobacterium
that a common cause underlies all
extorquens. The remarkable precision
these phenomena: the structure of
with which both studies quantifi ed
epistatic interactions among mutations.
epistasis among benefi cial mutations
Epistasis describes how the fi tness
was made possible only by leveraging
To quantify epistasis among beneficial
consequence of a mutation depends on the
whole-genome sequencing combined
mutations and to test these theoretical
status of the rest of the genome. In one
with the ability to reconstruct
predictions, both Khan et al. and Chou et
extreme example, called sign epistasis, a
mutational combinations and assay
al. examined the initial substitutions that
mutation may be benefi cial if it arises on one
them in the same environment in
occurred in populations of bacteria
genetic background, but detrimental on
which the mutations fi rst arose.
adapting in the laboratory. The researchers
another. Although interactions among genes
The view of epistasis across
identifi ed the handful of mutations across
may seem an obvious fact of biology, the
a genome that emerges from
the genome that had substituted in an
myriad possible forms of epistasis have made
this work contrasts sharply
evolved strain, and then constructed
it diffi cult to formuintermediate strains containing
combinations of these mutations. By
measuring the fi tness benefi ts conferred
by these muta-
Department of Biology, University of
Pennsylvania, Philadelphia, PA 19103, USA.
Department of Organismic and
Evolutionary Biology, Harvard University,
Cam bridge, MA 02138, USA. E -mail:
jplotkin@sas.upenn.edu
12
3 JUNE 2011
Published by AAAS
VOL 332
SCIENCE
www.sciencemag.org 1160
whether experiments in simple
environments, with only one or a few
niches for coexisting strains, will refl ect
with the type of epis tas is f ound the pattern of adaptation in more complex
am ong adaptive m utations w ithin ecologies, such as Pseudomonas fl
a s ingle protein ( 11). Notably,
uorescens in structured environments ( 6).
W einr eic h et al. s tudied
Nonetheless, the compelling consistency
m utations in an antibiotic
between these two studies should inspire
r es is tanc e gene, ß - lactam as e,
efforts to test the generality of their fi
and f ound a prevalence of s ign
ndings, by measuring epistasis in a wide
epis tas is, whic h lim its the num berrange of experimental and even natural
of genetic paths that evolution
systems.
c an follow ( 11). In c ontr as t, the
These
epis tas is doc um ented b y Khan et
studies, and
al. and Chou et al. exer ts less
the long-term
c ons tr aint on the or der of
laboratory
s ubs titutions that incr eas e fi
evolution
tness, s o that the speci fi c path
experiments
that evolution will tak e is less
from which
pr edic table. At the s am e tim e, the
they derive,
pr evalenc e of antagonis tic
represent a
epis tas is m eas ured b y the two
resounding
gr oups ens ures a pr edic table
achievement
tem po of adaptation
for the
c har ac terized by dim inis hing
reductionist
m ar ginal returns ( 10).
approach to
studying
Although these new experiments
biolog y. T he
suggest a consistent principle of how
mechanistic
epistasis shapes the pattern of
picture they
adaptation, many questions must be
paint of
answered before their results can be
evolution is
extended to evolution outside the
complex but
laboratory. It remains unclear, for
not
instance, whether these results would
incomprehens
be altered by changing fundamental
ible; although
evolutionary parameters, such as
epistatic
population size, rate of mutation, and
interactions
rate of recombination. Likewise, it is
lead to
unclear
surprising
phenomena,
the
G E N O M I C S
advantages of
a frozen
“fossil record”
of
laborator yrais
ed isolates,
and the ease
of
manipulating
—and, now,
fully
sequencing—ev
olved strains
enables
researchers to
tease apart and
examine the
underlying
causes of these
phenomena.
Moreover, the
theory and
concepts
developed to
explain these
simple
experiments
may have broad
pa yoffs.
Already,
PERSPECTIVESt h e n e x t m o v e s o f t h e m o s t
mutable and dangerous
human pathogens.
epistasis has been implicated
in the evolution of drug
resistance in infl uenza
viruses ( 12) and in bacterial
pathogens ( 13). Ultim ately,
populations of bacteria
tediously propagated in the
lab may be key to predicting
References
1. A. I. Khan, D. M. Dinh, D. Schneider, R. E.
Lenski, T. F. Cooper, Science 332, 1193 (2011).
2. H.-H. Chou, H.-C. Chiu, N. F. Delaney, D.
Segrè, C. J. Marx, Science 332, 1190 (2011).
3. S. F. Elena, R. E. Lenski, Nat. Rev. Genet. 4,
457 (2003). 4. P. D. Sniegowski, P. J. Gerrish, R.
E. Lenski, Nature 387,
703 (1997). 5. Z. D. Blount, C. Z. Borland, R.
Behavior and the Dynamic
Genome
E. Lenski, Proc. Natl. Acad.
Sci. U.S.A. 105, 7899 (2008). 6. P. B. Rainey,
M. Travisano, Nature 394, 69 (1998). 7. R. J. Woods
et al., Science 331, 1433 (2011). 8. A. S.
Kondrashov, Nature 336, 435 (1988). 9. G. P.
Wagner, L. Altenberg, Evolution 50, 967 (1996). 10.
S. Kryazhimskiy, G. Tkac ik, J. B. Plotkin, Proc. Natl.
Acad.
Sci. U.S.A. 106, 18638 (2009). 11. D. M.
Weinreich, N. F. Delaney, M. A. Depristo, D. L.
Hartl, Science 312, 111 (2006). 12. J. D. Bloom,
L. I. Gong, D. Baltimore, Science 328, 1272
(2010). 13. S. Trindade et al., PLoS Genet.
5, e1000578 (2009).
10.1126/science.1208072
Does behavior evolve through gene
expression changes in the brain in
response to the environment?
Alison M. 2 ,3 and Gene E.
Bell
Robinson
1, 3
ples ( 3), the latter as a
hen circumstances
over both physiological and
change, an
d r i v e r o f b e h a v i o r a l e v o l u t i o ne v o l u t i o n a r y t i m e s c a l e s ,
organism’s fi rst
has never been widely
provide a possible
response is often
accepted, perhaps as a
mechanism for how
behavior al. But how reaction against
behavioral plasticity might
does adapL a m a r c k i a n i s m — t h e i d e a t h a td r i v e r a p i d b e h a v i o r a l
t i v e b e h a v i o r e v o l v e , g i v e n t h a tc h a r a c t e r i s t i c s a c q u i r e d b y e v o l u t i o n t h r o u g h c h a n g e s
it requires constant and often h a b i t , u s e , o r d i s u s e c a n b e i n g e n e r e g u l a t i o n . I n a n
passed on across
environment with more
instantaneous interactions
g
e
n
e
r
a
t
i
o
n
s
.
H
o
w
e
v
e
r
,
predators, colonies
between an individual and its
b
e
h
a
v
i
o
r
a
l
g
e
n
e
t
i
c
s
a
n
d
producing more bees with
environment? The dominant
g
e
n
o
m
i
c
s
,
e
s
p
e
c
i
a
l
l
y
f
o
r
lower thresholds for
view em phasizes new random
a
n
i
m
a
l
s
i
n
n
a
t
u
r
a
l
responding to alarm
DNA mutation as the starting
populations, lend some
pheromone would have
point. This may lead to
p l a u s i b i l i t y t o t h e p h e n o t y p i cf a r e d b e t t e r , w h i c h w o u l d
behavioral variation. If the
plasticity view.
then result in a population
resulting variants have
with patterns of gene
different fi tness values, then The ability to analyze
g
e
n
o
m
e
w
i
d
e
g
e
n
e
expression whose output
natural selection could result
e
x
p
r
e
s
s
i
o
n
t
h
r
o
u
g
h
was an “aroused” behavior,
in behavioral evolution through
“
t
r
a
n
s
c
r
i
p
t
o
m
i
c
s
”
h
a
s
s
h
o
w
n
even in the absence of
changes in allele frequencies
t
h
a
t
t
h
e
g
e
n
o
m
e
r
e
s
p
o
n
d
s
alarm pheromone. Although
across generations. An
d ynam ically to stim uli ( 4).
this view does not rule out
alternative theory proposes
One illustrative example is
the possibility that these
environmentally induced
the honey bee. The African
differences in aggression
change in an organism’s
arose through new
b e h a v i o r a s t h e s t a r t i n g p o i n t (h o n e y b e e ( A p i s m e l l i f e r a
s
c
u
t
e
l
l
a
t
a
)
r
e
s
p
o
n
d
s
m
u
c
h
mutation, the
1) , and “ phenot ypic plas tic ity”
m
o
r
e
fi
e
r
c
e
l
y
w
h
e
n
i
t
s
h
i
v
e
transcriptomics agrees with
that is inherited across
i
s
a
t
t
a
c
k
e
d
t
h
a
n
d
o
o
t
h
e
r
the idea of “genetic
generations through an
accommodation” ( 3), the
s
u
b
s
p
e
c
i
e
s
o
f
h
o
n
e
y
b
e
e
.
unspecifi ed process of
Evolutionary changes in
modern, more inclusive
“genetic assim ilation” ( 2).
brain gene expression may
version of genetic
Despite numerous exam have resulted in an increase as s im i la t i on , w h ic h c o u l d
in responsiveness to alarm
involve either evolutionary
Department of Animal Biology,
pheromone (the chemical
increases or decreases in
University of Illinois,
Urbana-Champaign, IL 61801,
bees use to alert each other p la s t ic i t y. I n c ert a i n
U S A . Department of Entomology, University of Illinois,
to danger) for African honey e n v ir o nm e nts , p l as t ic
Urbana-Champaign, IL 61801, USA. Neuroscience
genotypes might be
Program, Program in Ecology, Evolutionary Biology and b e e s ( 5 ) . A b o u t 1 0 % o f t h e
favored, but in other
Conservation, Institute for Genomic Biology, University of s a m e g e n e s r e g u l a t e d i n t h e
Illinois, Urbana-Champaign, IL 61801, USA. E-mail:
brain by alarm pheromone
environments, nonplastic
generobi@life.uiuc.edu
are also differentially
genotypes might be
expressed between African
preferred instead. Future
and the less aggressive
studies will determine
European honey bees. These wh e th er d if f er enc es in
genes, acting
honey bee aggression can
be explained by selection
on regulatory regions of the
W
12
3
1161
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