Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Янв. 29, 2024
Abstract
The
endosymbiotic
bacteria
Wolbachia
can
invade
insect
populations
by
modifying
host
reproduction
through
cytoplasmic
incompatibility
(CI),
an
effect
that
results
in
embryonic
lethality
when
-carrying
males
mate
with
-free
females.
Here
we
describe
a
transgenic
system
for
recreating
CI
the
major
arbovirus
vector
Aedes
aegypti
using
factor
(
cif
)
genes
from
w
AlbB,
strain
currently
being
deployed
to
reduce
dengue
transmission.
CI-like
sterility
is
induced
cifA
and
cifB
are
co-expressed
testes;
this
rescued
maternal
expression,
thereby
reproducing
pattern
of
-induced
CI.
Expression
alone
associated
extensive
DNA
damage
disrupted
spermatogenesis.
strength
rescue
expression
dependent
on
comparative
levels
cifA/cifB
males.
These
findings
consistent
CifB
acting
as
toxin
CifA
antitoxin,
attenuating
toxicity
both
male
germline
developing
embryos.
provide
important
insights
into
interactions
between
their
mechanism
activity
foundation
building
gene-based
drive
Ae.
.
Язык: Английский
Cleave and Rescue gamete killers create conditions for gene drive in plants
Nature Plants,
Год журнала:
2024,
Номер
10(6), С. 936 - 953
Опубликована: Июнь 17, 2024
Язык: Английский
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2023,
Номер
11
Опубликована: Фев. 13, 2023
Gene
drive
is
a
genetic
engineering
technology
that
can
enable
super-mendelian
inheritance
of
specific
alleles,
allowing
them
to
spread
through
population.
New
gene
types
have
increased
flexibility,
offering
options
for
confined
modification
or
suppression
target
populations.
Among
the
most
promising
are
CRISPR
toxin-antidote
drives,
which
disrupt
essential
wild-type
genes
by
targeting
with
Cas9/gRNA.
This
results
in
their
removal,
increasing
frequency
drive.
All
these
drives
rely
on
having
an
effective
rescue
element,
consists
recoded
version
gene.
element
be
at
same
site
as
gene,
maximizing
chance
efficient
rescue,
distant
site,
allows
useful
such
easily
disrupting
another
confinement.
Previously,
we
developed
homing
haplolethal
and
haplosufficient
These
successful
had
functional
elements
but
suboptimal
efficiency.
Here,
attempted
construct
distant-site
configuration
from
three
loci
Drosophila
melanogaster
.
We
found
additional
gRNAs
cut
rates
nearly
100%.
However,
all
failed
both
genes.
Furthermore,
one
minimally
sequence
was
used
template
homology-directed
repair
different
chromosomal
arm,
resulting
formation
resistance
alleles.
Together,
inform
design
future
CRISPR-based
drives.
Язык: Английский
wMel replacement of dengue-competent mosquitoes is robust to near-term climate change
Nature Climate Change,
Год журнала:
2023,
Номер
13(8), С. 848 - 855
Опубликована: Авг. 1, 2023
Abstract
Rising
temperatures
are
impacting
the
range
and
prevalence
of
mosquito-borne
diseases.
A
promising
biocontrol
technology
replaces
wild
mosquitoes
with
those
carrying
virus-blocking
Wolbachia
bacterium.
Because
most
widely
used
strain,
w
Mel,
is
adversely
affected
by
heat
stress,
we
examined
how
global
warming
may
influence
Mel-based
replacement.
We
simulated
interventions
in
two
locations
successful
field
trials
using
Coupled
Model
Intercomparison
Project
Phase
5
climate
projections
historical
temperature
records,
integrating
empirical
data
on
Mel’s
thermal
sensitivity
into
a
model
Aedes
aegypti
population
dynamics
to
evaluate
introgression
persistence
over
one
year.
show
that
Cairns,
Australia,
climatic
futures
necessitate
operational
adaptations
for
heatwaves
exceeding
weeks.
In
Nha
Trang,
Vietnam,
projected
three
weeks
longer
eliminate
Mel
under
stringent
assumptions
symbiont’s
limits.
conclude
this
generally
robust
near-term
(2030s)
change.
Accelerated
challenge
2050s
beyond.
Язык: Английский
Performance characteristics allow for confinement of a CRISPR toxin–antidote gene drive for population suppression in a reaction–diffusion model
Proceedings of the Royal Society B Biological Sciences,
Год журнала:
2024,
Номер
291(2025)
Опубликована: Июнь 1, 2024
Gene
drive
alleles
that
can
bias
their
own
inheritance
could
engineer
populations
for
control
of
disease
vectors,
invasive
species
and
agricultural
pests.
There
are
successful
examples
suppression
drives
confined
modification
drives,
but
developing
has
proven
more
difficult.
However,
CRISPR-based
toxin–antidote
dominant
embryo
(TADE)
may
fill
this
niche.
It
works
by
targeting
disrupting
a
haplolethal
target
gene
in
the
germline
with
its
gRNAs
while
rescuing
target.
also
disrupts
female
fertility
driving
insertion
or
additional
gRNAs.
Here,
we
used
reaction–diffusion
model
to
assess
performance
continuous
space,
where
outcomes
be
substantially
different
from
those
panmictic
populations.
We
measured
wave
speed
found
moderate
fitness
costs
disruption
early
maternally
deposited
nuclease
eliminate
drive’s
ability
form
advance.
assessed
required
release
size,
finally
investigated
migration
corridor
scenarios.
is
often
possible
suppress
one
population
then
persist
without
invading
second
population,
potentially
desirable
outcome.
Thus,
even
imperfect
variants
TADE
excellent
candidates
suppression.
Язык: Английский
Making waves: Comparative analysis of gene drive spread characteristics in a continuous space model
Molecular Ecology,
Год журнала:
2023,
Номер
32(20), С. 5673 - 5694
Опубликована: Сен. 11, 2023
With
their
ability
to
rapidly
increase
in
frequency,
gene
drives
can
be
used
modify
or
suppress
target
populations
after
an
initial
release
of
drive
individuals.
Recent
advances
have
revealed
many
possibilities
for
different
types
drives,
and
several
these
been
realized
experiments.
These
advantages
disadvantages
related
ease
construction,
confinement
capacity
modification
suppression.
Though
characteristics
explored
modelling
studies,
assessment
continuous
space
environments
has
limited,
often
focusing
on
outcomes
rather
than
fundamental
properties.
Here,
we
conduct
a
comparative
analysis
that
the
form
wave
advance
using
individual-based
simulations
space.
We
evaluate
speed
as
function
performance
ecological
parameters,
which
reveals
substantial
differences
between
panmictic
versus
spatial
environments.
In
particular,
find
suppression
waves
are
uniquely
vulnerable
fitness
costs
undesired
CRISPR
cleavage
activity
embryos
by
maternal
deposition.
Some
however,
retain
robust
even
with
widely
varying
efficiency
parameters.
To
gain
better
understanding
waves,
compare
rate
wild-type
allele
removal
is
correlated
speed,
though
this
also
affected
other
factors.
Overall,
our
results
provide
useful
resource
spatially
environments,
may
most
representative
potential
deployment
relevant
scenarios.
Язык: Английский
Cleave and Rescue gamete killers create conditions for gene drive in plants
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 14, 2023
Abstract
Gene
drive
elements
promote
the
spread
of
linked
traits,
even
when
their
presence
confers
a
fitness
cost
to
carriers,
and
can
be
used
change
composition
or
fate
wild
populations.
Cleave
Rescue
(
ClvR
)
sit
at
fixed
chromosomal
position
include
DNA
sequence-modifying
enzyme
such
as
Cas9/gRNAs
(the
Cleaver/Toxin)
that
disrupts
endogenous
versions
an
essential
gene,
recoded
version
gene
resistant
cleavage
Rescue/Antidote).
spreads
by
creating
conditions
in
which
those
lacking
die
because
they
lack
functional
gene.
We
demonstrate
features
plant
Arabidopsis
thaliana
through
killing
gametes
fail
inherit
targets
YKT61,
whose
expression
is
required
male
female
for
survival.
Resistant
(uncleavable
but
functional)
alleles,
slow
prevent
drive,
were
not
observed.
Modeling
shows
s
are
likely
robust
certain
failure
modes
rapidly
population
modification
suppression.
Possible
applications
breeding,
weed
control,
conservation
discussed.
Язык: Английский
Modelling daisy quorum drive: A short-term bridge across engineered fitness valleys
PLoS Genetics,
Год журнала:
2024,
Номер
20(5), С. e1011262 - e1011262
Опубликована: Май 16, 2024
Engineered
gene-drive
techniques
for
population
modification
and/or
suppression
have
the
potential
tackling
complex
challenges,
including
reducing
spread
of
diseases
and
invasive
species.
Gene-drive
systems
with
low
threshold
frequencies
invasion,
such
as
homing-based
gene
drive,
require
initially
few
transgenic
individuals
to
are
therefore
easy
introduce.
The
self-propelled
behavior
drives
presents
a
double-edged
sword,
however,
can
allow
elements
expand
beyond
target
population.
By
contrast,
where
high
frequency
must
be
reached
before
alleles
spread—above
fitness
valley—are
less
susceptible
spillover
but
introduction
at
frequency.
We
model
proposed
drive
system,
called
“daisy
quorum
drive,”
that
transitions
over
time
from
low-threshold
daisy-chain
system
(involving
CRISPR-Cas9)
high-threshold
fitness-valley
(requiring
frequency—a
“quorum”—to
spread).
construct
temporarily
lowers
thresholds
required
construct,
facilitating
use
in
wide
variety
species
challenging
breed
release
large
numbers.
Because
daisy
chain
only
subsequent
not
themselves
also
carry
deleterious
(“drive
load”),
is
expected
exhaust
itself,
removing
all
CRISPR
leaving
whose
more
spatially
restricted.
Developing
analyzing
both
discrete
patch
continuous
space
models,
we
explore
how
various
attributes
affect
chance
modifying
local
characteristics
risk
area.
briefly
when
goal.
find
provide
promising
bridge
between
constructs,
allowing
short
term
better
containment
long
term,
without
requiring
repeated
introductions
or
persistence
elements.
Язык: Английский
Modeling emergence of Wolbachia toxin-antidote protein functions with an evolutionary algorithm
Frontiers in Microbiology,
Год журнала:
2023,
Номер
14
Опубликована: Июнь 9, 2023
Evolutionary
algorithms
(EAs)
simulate
Darwinian
evolution
and
adeptly
mimic
natural
evolution.
Most
EA
applications
in
biology
encode
high
levels
of
abstraction
top-down
population
ecology
models.
In
contrast,
our
research
merges
protein
alignment
from
bioinformatics
into
codon
based
EAs
that
molecular
string
the
bottom
up.
We
apply
to
reconcile
a
problem
field
Wolbachia
induced
cytoplasmic
incompatibility
(CI).
is
microbial
endosymbiont
lives
inside
insect
cells.
CI
conditional
sterility
operates
as
toxin
antidote
(TA)
system.
Although,
exhibits
complex
phenotypes
not
fully
explained
under
single
discrete
model.
instantiate
in-silico
genes
control
CI,
factors
(cifs),
strings
within
chromosome.
monitor
their
enzymatic
activity,
binding,
cellular
localization
by
applying
selective
pressure
on
primary
amino
acid
strings.
Our
model
helps
rationalize
why
two
distinct
mechanisms
induction
might
coexist
nature.
find
nuclear
signals
(NLS)
Type
IV
secretion
system
(T4SS)
are
low
complexity
evolve
fast,
whereas
binding
interactions
have
intermediate
complexity,
activity
most
complex.
predicts
ancestral
TA
systems
eukaryotic
systems,
placement
NLS
or
T4SS
can
stochastically
vary,
imparting
effects
impact
mechanics.
highlights
how
preconditions
sequence
length
bias
cifs
toward
one
mechanism
another.
Язык: Английский