Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost
Nature Microbiology,
Год журнала:
2024,
Номер
9(11), С. 3025 - 3040
Опубликована: Окт. 8, 2024
Язык: Английский
Widespread Deviant Patterns of Heterozygosity in Whole-Genome Sequencing Due to Autopolyploidy, Repeated Elements, and Duplication
Genome Biology and Evolution,
Год журнала:
2023,
Номер
15(12)
Опубликована: Дек. 1, 2023
Abstract
Most
population
genomic
tools
rely
on
accurate
single
nucleotide
polymorphism
(SNP)
calling
and
filtering
to
meet
their
underlying
assumptions.
However,
complexity,
resulting
from
structural
variants,
paralogous
sequences,
repetitive
elements,
presents
significant
challenges
in
assembling
contiguous
reference
genomes.
Consequently,
short-read
resequencing
studies
can
encounter
mismapping
issues,
leading
SNPs
that
deviate
Mendelian
expected
patterns
of
heterozygosity
allelic
ratio.
In
this
study,
we
employed
the
ngsParalog
software
identify
such
deviant
whole-genome
sequencing
(WGS)
data
with
low
(1.5×)
intermediate
(4.8×)
coverage
for
four
species:
Arctic
Char
(Salvelinus
alpinus),
Lake
Whitefish
(Coregonus
clupeaformis),
Atlantic
Salmon
(Salmo
salar),
American
Eel
(Anguilla
rostrata).
The
analyses
revealed
accounted
22%
62%
all
salmonid
datasets
approximately
11%
dataset.
These
were
particularly
concentrated
within
elements
regions
had
recently
undergone
rediploidization
salmonids.
Additionally,
narrow
peaks
elevated
ubiquitous
along
genomes,
encompassed
most
SNPs,
could
be
partially
associated
transposons
tandem
repeats.
Including
these
led
highly
distorted
site
frequency
spectra,
underestimated
pairwise
FST
values,
overestimated
diversity.
Considering
widespread
occurrence
arising
a
variety
sources,
important
impact
estimating
parameters,
availability
effective
them,
propose
excluding
WGS
is
required
improve
inferences
wide
range
taxa
depths.
Язык: Английский
The good, the bad and the ugly of transposable elements annotation tools
Genetics and Molecular Biology,
Год журнала:
2023,
Номер
46(3 suppl 1)
Опубликована: Янв. 1, 2023
Transposable
elements
are
repetitive
and
mobile
DNA
segments
that
can
be
found
in
virtually
all
organisms
investigated
to
date.
Their
complex
structure
variable
nature
particularly
challenging
from
the
genomic
annotation
point
of
view.
Many
softwares
have
been
developed
automate
facilitate
TEs
at
level,
but
they
highly
heterogeneous
regarding
documentation,
usability
methods.
In
this
review,
we
revisited
existing
software
for
TE
annotation,
concentrating
on
most
often
used
ones,
methodologies
apply,
usability.
Building
state
art
propose
best
practices
highlight
strengths
weaknesses
available
solutions.
Язык: Английский
Most azole antifungal resistance mutations in the drug target provide cross-resistance and carry no intrinsic fitness cost
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 14, 2023
Abstract
Azole
antifungals
are
among
the
most
frequently
used
drugs
to
treat
fungal
infections.
Amino
acid
substitutions
in
and
around
binding
site
of
azole
target
Erg11
(Cyp51)
a
common
resistance
mechanism
pathogenic
yeasts
such
as
Candida
albicans
.
How
many
which
mutations
confer
resistance,
at
what
cost,
is
however
largely
unknown.
Here,
we
measure
impact
nearly
4,000
amino
variants
ligand
pocket
on
susceptibility
six
medical
azoles.
We
find
that
large
fraction
lead
(33%),
cross-resistance
two
or
more
azoles
(88%)
importantly,
only
handful
show
significant
fitness
cost
absence
drug
(9%).
Our
results
reveal
can
arise
through
set
this
will
likely
pan-resistance,
with
very
little
evolutionary
compromise.
Such
resource
help
inform
treatment
choices
clinical
settings
guide
development
new
drugs.
Язык: Английский
Regulatory logic and transposable element dynamics in nematode worm genomes
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
Abstract
Genome
sequencing
has
revealed
a
tremendous
diversity
of
transposable
elements
(TEs)
in
eukaryotes
but
there
is
little
understanding
the
evolutionary
processes
responsible
for
TE
diversity.
Non-autonomous
TEs
have
lost
machinery
necessary
transposition
and
rely
on
closely
related
autonomous
critical
proteins.
We
studied
two
mathematical
models
regulation,
one
assuming
that
both
tranposons
their
non-autonomous
relatives
operate
under
same
regulatory
logic,
competing
resources,
self-attenuate
while
transposons
continually
increase,
parasitizing
relatives.
implemented
these
stochastic
simulations
how
relationships
influence
populations.
found
only
outcrossing
populations
evolving
with
Parasitic
regulation
resulted
stable
maintenance
TEs.
tested
our
model
predictions
Caenorhabditis
genomes
by
annotating
focal
families,
LINEs
SINE
DNA
transposon
Mutator
.
broad
variation
-
rapid
mutational
decay
sequences
allow
to
transpose.
Together,
results
suggest
individual
families
evolve
according
disparate
rules
are
relevant
early,
acute
stages
invasion.
Язык: Английский