Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(40)
Опубликована: Сен. 20, 2023
With
advancements
in
stem
cell
technology,
vitro
models
using
iPSC
(induced
pluripotent
cells)-derived
cardiomyocytes
(iPSC-CM)
and
engineered
heart
tissues
(EHT)
can
serve
as
powerful
tools
for
disease
modeling
drug
screening.
...Fluorescent
reporters
of
cardiac
electrophysiology
provide
valuable
information
on
tissue
function.
However,
motion
artifacts
caused
by
muscle
contraction
interfere
with
accurate
measurement
fluorescence
signals.
Although
drugs
...
Genome Biology and Evolution,
Год журнала:
2024,
Номер
16(2)
Опубликована: Янв. 11, 2024
Abstract
Disentangling
the
effects
of
demography
and
selection
has
remained
a
focal
point
population
genetic
analysis.
Knowledge
about
mutation
recombination
is
essential
in
this
endeavor;
however,
despite
clear
evidence
that
both
rates
vary
across
genomes,
it
common
practice
to
model
as
fixed.
In
study,
we
quantify
how
unaccounted
for
rate
heterogeneity
may
impact
inference
using
approaches
inferring
(DFE-alpha,
Grapes,
polyDFE)
and/or
(fastsimcoal2
δaδi).
We
demonstrate
that,
if
not
properly
modeled,
can
increase
uncertainty
estimation
demographic
selective
parameters
some
scenarios
result
mis-leading
inference.
These
results
highlight
importance
quantifying
fundamental
evolutionary
before
utilizing
genomic
data
drift
(i.e.
modulated
by
history)
selection;
or,
at
least,
these
should
be
directly
modeled
downstream
Genome Biology and Evolution,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
Abstract
The
nocturnal
aye-aye,
Daubentonia
madagascariensis,
is
one
of
the
most
elusive
lemurs
on
island
Madagascar.
timing
its
activity
and
arboreal
lifestyle
has
generally
made
it
difficult
to
obtain
accurate
assessments
population
size
using
traditional
census
methods.
Therefore,
alternative
estimates
provided
by
genetic
inference
are
essential
for
yielding
much
needed
information
conservation
measures
enabling
ecological
evolutionary
studies
this
species.
Here,
we
utilize
genomic
data
from
17
individuals—including
5
newly
sequenced,
high-coverage
genomes—to
estimate
history.
Essential
estimation
recently
published
annotations
aye-aye
genome
which
allow
variation
at
putatively
neutral
regions
be
included
in
procedures,
subject
selective
constraints,
or
linkage
such
sites,
excluded
owing
biasing
effects
selection
demographic
inference.
By
comparing
a
variety
tools
develop
well-supported
model
history,
find
strong
support
two
demes,
separating
northern
Madagascar
rest
island.
Additionally,
that
experienced
severe
reductions
size.
first
occurred
rapidly,
approximately
3,000
5,000
years
ago,
likely
corresponded
with
arrival
humans
second
over
past
few
decades
related
substantial
habitat
loss,
suggesting
species
still
undergoing
decline
remains
great
risk
extinction.
Evolution,
Год журнала:
2023,
Номер
77(10), С. 2113 - 2127
Опубликована: Июнь 30, 2023
The
detection
of
selective
sweeps
from
population
genomic
data
often
relies
on
the
premise
that
beneficial
mutations
in
question
have
fixed
very
near
sampling
time.
As
it
has
been
previously
shown
power
to
detect
a
sweep
is
strongly
dependent
time
since
fixation
as
well
strength
selection,
naturally
case
strong,
recent
leave
strongest
signatures.
However,
biological
reality
enter
populations
at
rate,
one
partially
determines
mean
wait
between
events
and
hence
their
age
distribution.
An
important
thus
remains
about
recurrent
when
they
are
modeled
by
realistic
mutation
rate
part
distribution
fitness
effects,
opposed
single,
recent,
isolated
event
purely
neutral
background
more
commonly
modeled.
Here
we
use
forward-in-time
simulations
study
performance
used
statistics,
within
context
evolutionary
baseline
models
incorporating
purifying
size
change,
recombination
heterogeneity.
Results
demonstrate
interplay
these
processes,
necessitating
caution
interpreting
selection
scans;
specifically,
false-positive
rates
excess
true-positive
across
much
evaluated
parameter
space,
undetectable
unless
exceptionally
strong.
G3 Genes Genomes Genetics,
Год журнала:
2024,
Номер
14(6)
Опубликована: Март 29, 2024
Abstract
The
role
of
balancing
selection
in
maintaining
genetic
variation
remains
an
open
question
population
genetics.
Recent
years
have
seen
numerous
studies
identifying
candidate
loci
potentially
experiencing
selection,
most
predominantly
human
populations.
There
are
however
alternative
evolutionary
processes
that
may
leave
similar
patterns
variation,
thereby
confounding
inference,
and
the
expected
signatures
additionally
change
a
temporal
fashion.
Here
we
use
forward-in-time
simulations
to
quantify
statistical
power
detect
using
both
site
frequency
spectrum-
linkage
disequilibrium-based
methods
under
variety
evolutionarily
realistic
null
models.
We
find
whilst
spectrum-based
little
immediately
after
balanced
mutation
begins
segregating,
increases
with
time
since
introduction
allele.
Conversely,
considerable
allele
is
young,
dissipates
rapidly
as
increases.
Taken
together,
this
suggests
effective
at
detecting
long-term
(>25N
generations
allele)
over
much
shorter
timescales
(<1N
generations),
leaving
large
frame
which
current
action
selection.
Finally,
investigate
extent
mimic
these
patterns,
demonstrate
need
for
caution
attempting
distinguish
from
those
neutral
(e.g.
structure
admixture)
well
selective
partial
sweeps).
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 22, 2024
The
demographic
history
of
a
population,
and
the
distribution
fitness
effects
(DFE)
newly
arising
mutations
in
functional
genomic
regions,
are
fundamental
factors
dictating
both
genetic
variation
evolutionary
trajectories.
Although
DFE
inference
has
been
performed
extensively
humans,
these
approaches
have
generally
either
limited
to
simple
models
involving
single
or,
where
complex
population
inferred,
without
accounting
for
potentially
confounding
selection
at
linked
sites.
Taking
advantage
coding-sparse
nature
genome,
we
propose
2-step
approach
which
coalescent
simulations
first
used
infer
multi-population
model,
utilizing
large
non-functional
regions
that
likely
free
from
background
selection.
We
then
use
forward-in-time
perform
conditional
on
demography
inferred
expected
estimation
procedure.
Throughout,
recombination
mutation
rate
maps
were
account
underlying
empirical
heterogeneity
across
human
genome.
Importantly,
within
this
framework
it
is
possible
utilize
fit
multiple
aspects
data,
scheme
represents
generalized
such
large-scale
species
with
genomes.
Genome Biology and Evolution,
Год журнала:
2023,
Номер
15(11)
Опубликована: Ноя. 1, 2023
Abstract
The
global
impact
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
has
led
to
considerable
interest
in
detecting
novel
beneficial
mutations
and
other
genomic
changes
that
may
signal
the
development
variants
concern
(VOCs).
ability
accurately
detect
these
within
individual
patient
samples
is
important
enabling
early
detection
VOCs.
Such
scans
for
rarely
acting
positive
selection
are
best
performed
via
comparison
empirical
data
with
simulated
wherein
commonly
evolutionary
factors,
including
mutation
recombination,
reproductive
infection
dynamics,
purifying
background
selection,
can
be
carefully
accounted
parameterized.
Although
there
been
work
quantify
factors
SARS-CoV-2,
they
have
yet
integrated
into
a
baseline
model
describing
intrahost
dynamics.
To
construct
such
model,
we
develop
simulation
framework
enables
one
establish
expectations
underlying
levels
patterns
patient-level
variation.
By
varying
eight
key
parameters,
evaluated
12,096
different
model–parameter
combinations
compared
them
existing
data.
Of
these,
592
models
(∼5%)
were
plausible
based
on
resulting
mean
expected
number
segregating
variants.
These
shared
several
commonalities
shedding
light
SARS-CoV-2
dynamics:
bottlenecks,
low
skew,
distribution
fitness
effects
skewed
toward
strongly
deleterious
mutations.
We
also
describe
areas
uncertainty
highlight
additional
sequence
help
further
refine
model.
This
study
lays
groundwork
improved
analysis
future
within-patient
Molecular Biology and Evolution,
Год журнала:
2024,
Номер
41(7)
Опубликована: Июнь 14, 2024
Inferring
the
demographic
history
of
populations
provides
fundamental
insights
into
species
dynamics
and
is
essential
for
developing
a
null
model
to
accurately
study
selective
processes.
However,
background
selection
sweeps
can
produce
genomic
signatures
at
linked
sites
that
mimic
or
mask
signals
associated
with
historical
population
size
change.
While
theoretical
biases
introduced
by
effects
have
been
well
established,
it
unclear
whether
ancestral
recombination
graph
(ARG)-based
approaches
inference
in
typical
empirical
analyses
are
susceptible
misinference
due
these
effects.
To
address
this,
we
developed
highly
realistic
forward
simulations
human
Drosophila
melanogaster
populations,
including
empirically
estimated
variability
gene
density,
mutation
rates,
purifying,
positive
selection,
across
different
scenarios,
broadly
assess
impact
on
using
genealogy-based
approach.
Our
results
indicate
minimally
although
could
cause
similar
genome
architecture
parameters
experiencing
more
frequent
recurrent
sweeps.
We
found
accurate
D.
ARG-based
methods
compromised
presence
pervasive
alone,
leading
spurious
inferences
recent
expansion,
which
may
be
further
worsened
sweeps,
depending
proportion
strength
beneficial
mutations.
Caution
additional
testing
species-specific
needed
when
inferring
non-human
avoid
selection.