Maintenance
of
rod-shape
in
bacterial
cells
depends
on
the
actin-like
protein
MreB.
Deletion
mreB
from
Pseudomonas
fluorescens
SBW25
results
viable
spherical
variable
volume
and
reduced
fitness.
Using
a
combination
time-resolved
microscopy
biochemical
assay
peptidoglycan
synthesis
we
show
that
fitness
is
consequence
perturbed
cell
size
homeostasis
arises
primarily
differential
growth
daughter
cells.
A
1,000-generation
selection
experiment
resulted
rapid
restoration
with
derived
retaining
shape.
Mutations
Pbp1A
were
identified
as
main
route
for
genetic
reconstructions
demonstrating
causality.
The
pbp1A
mutations
targeting
transpeptidase
activity
enhance
homogeneity
wall
lateral
surfaces,
thus
restoring
population.
Together
our
experimental
approach
emphasizes
new
knowledge
to
be
gained
strategies
exploit
power
natural
rescue
fitness-compromised
mutants.
Current Biology,
Год журнала:
2019,
Номер
29(18), С. 3081 - 3086.e5
Опубликована: Сен. 1, 2019
One
of
the
most
long-standing
and
important
mysteries
in
evolutionary
biology
is
why
biological
diversity
so
unevenly
distributed
across
space
taxonomic
lineages.
Nowhere
this
disparity
more
evident
than
multitude
rapid
radiations
found
on
oceanic
islands
mountain
ranges
globe
[1Schluter
D.
The
Ecology
Adaptive
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University
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J.T.
Losos
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G.G.
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H.P.
Plant
species
radiations:
where,
when,
why?.Philos.
Trans.
R.
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Biol.
Sci.
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C.E.
Atchison
G.W.
ubiquity
alpine
plant
from
Andes
to
Hengduan
Mountains.New
Phytol.
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207:
275-282Crossref
(209)
Scholar].
processes
driving
these
diversification
events
remain
unclear
[6Simões
M.
Breitkreuz
L.
Alvarado
Baca
S.
Cooper
J.C.
Heins
Herzog
K.
Lieberman
B.S.
evolving
theory
radiations.Trends
31:
27-34Abstract
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Text
PDF
(118)
7Rundell
R.J.
Price
T.D.
radiation,
nonadaptive
ecological
speciation
nonecological
speciation.Trends
2009;
24:
394-399Abstract
(395)
8Givnish
T.J.
radiation
versus
'radiation'
'explosive
diversification':
conceptual
distinctions
are
fundamental
understanding
evolution.New
297-303Crossref
(126)
Recent
genome-wide
studies
suggest
that
natural
selection
may
be
frequent
during
radiations,
as
inferred
work
cichlid
fish
[9Brawand
Wagner
Li
Y.I.
Malinsky
Keller
I.
Fan
Simakov
O.
Ng
A.Y.
Lim
Z.W.
Bezault
E.
et
al.The
genomic
substrate
for
African
fish.Nature.
2014;
513:
375-381Crossref
(639)
Scholar],
white-eye
birds
[10Cornetti
Valente
L.M.
Dunning
L.T.
Quan
X.
Black
R.A.
Hébert
Savolainen
V.
genome
"Great
Speciator"
provides
insights
into
bird
diversification.Genome
7:
2680-2691Crossref
(32)
new
world
lupins
[11Nevado
B.
Hughes
Filatov
D.A.
Widespread
evolution
repeated
New
World
lupins.Nat.
Commun.
12384Crossref
(56)
wild
tomatoes
[12Pease
Haak
D.C.
Hahn
M.W.
Moyle
L.C.
Phylogenomics
reveals
three
sources
variation
a
radiation.PLoS
14:
e1002379Crossref
(212)
However,
whether
general
feature
remains
untested.
Here
we
show
significantly
compared
background
levels
slowly
diversifying
This
result
consistent
wide
range
angiosperm
lineages
analyzed:
12
which
together
comprise
1,377
described
species,
originating
some
biologically
diverse
systems
Earth.
In
addition,
find
significant
negative
correlation
between
population
size
frequency
radiations.
A
possible
explanation
pattern
at
least
partly
driven
by
positive
advantageous
mutations
compensate
fixation
slightly
deleterious
smaller
populations.
Many
biological
features
are
conserved
and
thus
considered
to
be
resistant
evolutionary
change.
While
rapid
genetic
adaptation
following
the
removal
of
genes
has
been
observed,
we
often
lack
a
mechanistic
understanding
how
happens.
We
used
budding
yeast,
Saccharomyces
cerevisiae,
investigate
plasticity
chromosome
metabolism,
network
modules.
experimentally
evolved
cells
constitutively
experiencing
DNA
replication
stress
caused
by
absence
Ctf4,
protein
that
coordinates
enzymatic
activities
at
forks.
Parallel
populations
adapted
stress,
over
1000
generations,
acquiring
multiple,
concerted
mutations.
These
mutations
altered
two
metabolism
modules,
sister
chromatid
cohesion,
inactivated
third,
damage
checkpoint.
The
selected
define
functionally
reproducible
trajectory.
suggest
implications
for
genome
evolution
in
natural
cancer.All
plants,
animals
fungi
share
common
ancestor,
though
they
have
become
very
distinct
billions
years,
all
essential
machinery
needed
grow
divide.
At
heart
this
is
complex
interaction
proteins
involved
replication,
process
duplicating
material
every
time
cell
divides.
needs
done
with
great
care,
error
rates
as
small
one
mistake
billion.
Otherwise,
can
accumulate
genome,
causing
problems
long-term
survival.
Despite
overall
principles
remaining
same,
underlying
mechanisms
vary
across
different
organisms.
Given
precision
complexity
replicating
DNA,
it
was
not
clear
had
differences.
Fumasoni
Murray
set
out
answer
forcing
strain
yeast
evolve
removing
gene
an
important,
but
essential,
component
replication.
were
still
able
reproduce,
hampered
mutation.
studied
after
reproduced
thousand
giving
enough
acquire
new
would
allow
compensate
initial
defects.
In
eight
separate
samples,
made
many
same
changes
order
overcome
original
segregation
third
feature
normally
protect
against
accumulation
damaged
DNA.
findings
show
pathways
controlled,
laboratory
environment
quickly
processes
damaged.
behavior
mutated
mimicked
cancer
cells,
which
struggling
adapt
their
machinery.
Studying
follows
perturbations
could
help
researchers
better
deal
challenges
treatment
development
antibiotic
resistance
bacteria,
well
leading
deeper
both
biology.
The
most
common
cause
of
human
congenital
disorders
glycosylation
(CDG)
are
mutations
in
the
phosphomannomutase
gene
PMM2,
which
affect
protein
N
-linked
glycosylation.
yeast
SEC53
encodes
a
homolog
PMM2
.
We
evolved
384
populations
harboring
one
two
human-disease-associated
alleles,
sec53-
V238M
and
sec53
-F126L,
or
wild-type
find
that
after
1000
generations,
compensate
for
slow-growth
phenotype
associated
with
alleles.
Through
whole-genome
sequencing
we
identify
compensatory
mutations,
including
known
genetic
interactors.
observe
an
enrichment
other
genes
whose
homologs
Type
1
CDG,
PGM1
,
minor
isoform
phosphoglucomutase
yeast.
By
reconstruction,
show
pgm1
dominant
allele-specific
interactors
restore
both
growth
-V238M
allele.
Finally,
characterize
enzymatic
activity
purified
Pgm1
mutant
proteins.
reduction,
but
not
elimination,
best
compensates
deleterious
phenotypes
Broadly,
our
results
demonstrate
power
experimental
evolution
as
tool
identifying
pathways
Cell Reports,
Год журнала:
2025,
Номер
44(2), С. 115323 - 115323
Опубликована: Фев. 1, 2025
Microtubules
are
polymers
required
for
chromosome
segregation.
Their
drug-induced
hyperstabilization
impairs
segregation
and
is
an
established
anti-cancer
therapy.
How
cells
respond
to
microtubule
hyperstabilization,
however,
incompletely
understood.
To
study
this,
we
evolved
budding
yeast
expressing
a
microtubule-hyperstabilizing
tubulin
mutant
isolated
adapted
strains.
Aneuploidy
of
specific
chromosomes
carrying
the
regulators
STU2
VIK1/KAR3
was
first
observable
adaptation.
In
longer
run,
aneuploidies
were
outcompeted
by
mutations
in
α-
or
β-tubulin,
partially
overlapping
with
cancer
patients.
Thus,
compensation
follows
restrained
reproducible
path
where
new
combine
original
offending
mutation
on
same
carrier.
While
partly
compensatory,
several
failed
re-establish
fully
normal
dynamics.
Sustained
growth
relied
mitotic
checkpoint,
indicating
that
extended
timing
limits
genomic
instability
caused
reduced
Our
results
predict
potential
vulnerability
resistant
agents.
Maintenance
of
rod-shape
in
bacterial
cells
depends
on
the
actin-like
protein
MreB.
Deletion
mreB
from
Pseudomonas
fluorescens
SBW25
results
viable
spherical
variable
volume
and
reduced
fitness.
Using
a
combination
time-resolved
microscopy
biochemical
assay
peptidoglycan
synthesis,
we
show
that
fitness
is
consequence
perturbed
cell
size
homeostasis
arises
primarily
differential
growth
daughter
cells.
A
1,000-generation
selection
experiment
resulted
rapid
restoration
with
derived
retaining
shape.
Mutations
synthesis
Pbp1A
were
identified
as
main
route
for
evolutionary
rescue
genetic
reconstructions
demonstrating
causality.
Compensatory
pbp1A
mutations
targeted
transpeptidase
activity
enhanced
homogeneity
wall
lateral
surfaces
restored
homeostasis.
Mechanistic
explanations
require
understanding
why
deletion
causes
heterogeneity
synthesis.
We
conclude
by
presenting
two
testable
hypotheses,
one
which
posits
stems
non-functional
machinery,
while
second
machinery
functional,
albeit
stalled.
Overall,
our
data
provide
support
hypothesis
draw
attention
to
importance
balance
between
glycosyltransferase
functions
building
enzymes
shape
determination.
Maintenance
of
rod-shape
in
bacterial
cells
depends
on
the
actin-like
protein
MreB.
Deletion
mreB
from
Pseudomonas
fluorescens
SBW25
results
viable
spherical
variable
volume
and
reduced
fitness.
Using
a
combination
time-resolved
microscopy
biochemical
assay
peptidoglycan
synthesis,
we
show
that
fitness
is
consequence
perturbed
cell
size
homeostasis
arises
primarily
differential
growth
daughter
cells.
A
1000-generation
selection
experiment
resulted
rapid
restoration
with
derived
retaining
shape.
Mutations
synthesis
Pbp1A
were
identified
as
main
route
for
evolutionary
rescue
genetic
reconstructions
demonstrating
causality.
Compensatory
pbp1A
mutations
targeted
transpeptidase
activity
enhanced
homogeneity
wall
lateral
surfaces
restored
homeostasis.
Mechanistic
explanations
require
understanding
why
deletion
causes
heterogeneity
synthesis.
We
conclude
by
presenting
two
testable
hypotheses,
one
which
posits
stems
non-functional
machinery,
while
second
machinery
functional,
albeit
stalled.
Overall,
our
data
provide
support
hypothesis
draw
attention
to
importance
balance
between
glycosyltransferase
functions
building
enzymes
shape
determination.
PLoS Biology,
Год журнала:
2020,
Номер
18(3), С. e3000635 - e3000635
Опубликована: Март 10, 2020
The
role
of
proteins
often
changes
during
evolution,
but
we
do
not
know
how
cells
adapt
when
a
protein
is
asked
to
participate
in
different
biological
function.
We
forced
the
budding
yeast,
Saccharomyces
cerevisiae,
use
meiosis-specific
kleisin,
recombination
8
(Rec8),
mitotic
cell
cycle,
instead
its
paralog,
Scc1.
This
perturbation
impairs
sister
chromosome
linkage,
advances
timing
genome
replication,
and
reduces
reproductive
fitness
by
45%.
evolved
15
parallel
populations
for
1,750
generations,
substantially
increasing
their
fitness,
analyzed
genotypes
phenotypes
cells.
Only
one
population
contained
mutation
Rec8,
many
had
mutations
transcriptional
mediator
complex,
cohesin-related
genes,
cycle
regulators
that
induce
S
phase.
These
improve
cohesion
delay
replication
Rec8-expressing
conclude
known
novel
partners
allow
an
existing
new
functions.