Biological
differences
between
males
and
females
lead
to
many
in
physiology,
disease,
overall
health.
One
of
the
most
prominent
disparities
is
number
germline
mutations
passed
offspring:
human
transmit
three
times
as
do
females.
While
classic
explanation
for
this
pattern
invokes
post-puberty
replication
sexes,
recent
whole-genome
evidence
humans
other
mammals
has
cast
doubt
on
mechanism.
Here,
we
review
work
that
inconsistent
with
a
replication-driven
model
male-biased
mutation,
propose
an
alternative,
“faulty
male”
hypothesis.
Importantly,
suggest
new
mutation
may
also
help
explain
several
pronounced
sexes
cancer,
aging,
DNA
repair.
Although
detailed
contributions
genetic,
epigenetic,
hormonal
influences
biological
sex
remain
be
fully
understood,
reconsideration
mechanisms
underlying
these
will
deeper
understanding
evolution
disease.
PLoS Genetics,
Journal Year:
2024,
Volume and Issue:
20(2), P. e1011129 - e1011129
Published: Feb. 12, 2024
Lewontin's
paradox,
the
observation
that
levels
of
genetic
diversity
(π)
do
not
scale
linearly
with
census
population
size
(Nc)
variation,
is
an
evolutionary
conundrum.
The
most
extreme
mismatches
between
π
and
Nc
are
found
for
highly
abundant
marine
invertebrates.
Yet,
influences
new
mutations
on
relative
to
extrinsic
processes
such
as
fluctuations
unknown.
Here,
we
provide
first
germline
mutation
rate
(μ)
estimate
a
invertebrate
in
corallivorous
crown-of-thorns
sea
stars
(Acanthaster
cf.
solaris).
We
use
high-coverage
whole-genome
sequencing
14
parent-offspring
trios
alongside
empirical
estimates
Australia's
Great
Barrier
Reef
jointly
examine
determinants
populations
undergoing
fluctuations.
A.
solaris
mean
μ
was
9.13
x
10-09
per-site
per-generation
(95%
CI:
6.51
1.18
10-08),
exceeding
other
invertebrates
showing
greater
concordance
vertebrate
rates.
Lower-than-expected
Ne
(~70,000-180,000)
low
Ne/Nc
values
(0.0047-0.048)
indicated
weak
outbreaks
long-term
π.
Our
findings
consistent
elevated
evolving
response
reduced
generation
time
length,
important
implications
explaining
high
mutational
loads
taxa.
Journal of Veterinary Internal Medicine,
Journal Year:
2024,
Volume and Issue:
38(4), P. 2316 - 2323
Published: June 10, 2024
Abstract
Background
Regional
lymph
nodes
are
frequently
sampled
in
cats
with
suspected
intestinal
lymphoma;
however,
their
diagnostic
value
has
not
been
explored.
Objectives
To
investigate
whether
histologic
and
immunohistochemical
analysis
of
mesenteric
correlates
the
diagnosis
lymphoma
cats.
Animals
One
hundred
2
client‐owned
diagnosed
lymphoma.
Methods
Retrospective
study.
The
inclusion
criteria
required
a
full‐thickness
biopsy
small
intestine
concurrent
excision
nodes.
Histologic
immunophenotypic
analyses
were
performed
on
biopsies
corresponding
Selected
nodal
samples
reactive
underwent
clonality
testing.
Results
Transmural
T‐cell
lymphomas,
encompassing
large
cell
types,
predominant
(64
cases,
62.7%),
B‐cell
lymphomas
being
more
transmural
(68.8%)
than
mucosal
(31.2%).
Among
all
examined,
44
(43.1%;
95%
CI:
33.9%‐52.8%)
exhibited
neoplastic
infiltration.
cases
lymphoma,
51
out
72
(70.8%;
59.4%‐80.1%)
showed
no
involvement.
Clonality
results
correctly
identified
19/30
(63.3%;
45.5%‐78.2%)
Concerns
raised
regarding
clonal
identification
remaining
potential
misdiagnoses
based
phenotypic
characteristics.
Conclusion
Clinical
Importance
study
underscores
drawbacks
relying
solely
for
diagnosing
cats,
particularly
subtypes.
It
emphasizes
importance
assessing
infiltration
recommends
caution
when
utilizing
histologic,
evaluations
lymphomas.
Despite
limitations,
this
research
highlights
need
comprehensive
strategies
Molecular Biology and Evolution,
Journal Year:
2025,
Volume and Issue:
42(4)
Published: March 25, 2025
Abstract
Rates
of
molecular
evolution
are
known
to
vary
across
species,
often
deviating
from
the
classical
expectation
a
strict
clock.
In
many
cases,
rate
has
been
found
correlate
generation
time,
an
effect
that
could
be
explained
if
species
with
shorter
times
have
higher
mutation
rates
per
year.
We
investigate
this
hypothesis
using
direct
estimates
for
133
eukaryotic
diverse
taxonomic
groups.
Using
phylogenetic
comparative
approach,
we
find
strong
negative
correlation
between
year
and
consistent
all
Our
results
provide
simple
explanation
why
time
plays
pivotal
role
in
driving
eukaryotes.
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(21)
Published: May 20, 2025
Mutation
rates
vary
across
the
tree
of
life
by
many
orders
magnitude,
with
fewer
mutations
occurring
each
generation
in
species
that
reproduce
quickly
and
maintain
large
effective
population
sizes.
A
compelling
explanation
is
sizes
facilitate
selection
against
weakly
deleterious
“mutator
alleles”
such
as
variants
modulate
cell
division
or
interfere
molecular
efficacy
DNA
repair.
However,
while
fidelity
a
single
largely
determines
microorganisms’
mutation
rates,
relationship
rate
to
determinants
damage
repair
more
complex
multicellular
long
times.
Since
generations
leave
time
for
accrue
generation,
we
posit
likely
amplifies
fitness
consequences
any
agent
defect
creates
extra
spermatogonia
oocytes.
This
leads
counterintuitive
prediction
highest
germline
per
are
also
most
mechanisms
avoiding
repairing
their
reproductive
cells.
Consistent
this,
show
cells
inversely
correlated
time;
contrast,
number
occur
during
prepuberty
development
trends
upward
increases.
Our
results
parallel
recent
findings
longest-lived
have
lowest
adult
somatic
tissues,
potentially
due
keep
lifetime
load
below
harmful
threshold.
Molecular Biology and Evolution,
Journal Year:
2023,
Volume and Issue:
40(9)
Published: Aug. 30, 2023
Mutation
rate
is
a
fundamental
parameter
in
population
genetics.
Apart
from
being
an
important
scaling
for
demographic
and
phylogenetic
inference,
it
allows
one
to
understand
at
what
new
genetic
diversity
generated
the
expected
level
of
equilibrium.
However,
except
well-established
model
organisms,
accurate
estimates
de
novo
mutation
rates
are
available
very
limited
number
organisms
wild.
We
estimated
(µ)
two
marine
populations
nine-spined
stickleback
(Pungitius
pungitius)
with
aid
several
2-
3-generational
family
pedigrees,
deep
(>50×)
whole-genome
resequences
high-quality
reference
genome.
After
stringent
filtering,
we
discovered
308
germline
mutations
106
offspring
translating
µ
=
4.83
×
10-9
4.29
per
base
generation
populations,
respectively.
Up
20%
were
shared
by
full-sibs
showing
that
parental
mosaicism
was
relatively
high.
Since
3.1
times
smaller
than
commonly
used
substitution
rate,
recalibration
led
substantial
increase
divergence
between
different
species.
Our
should
provide
useful
resource
research
focused
on
fish
genetics
sticklebacks
particular.
Molecular Biology and Evolution,
Journal Year:
2023,
Volume and Issue:
40(12)
Published: Nov. 21, 2023
Even
in
the
genomics
era,
phylogeny
of
Neotropical
small
felids
comprised
genus
Leopardus
remains
contentious.
We
used
whole-genome
resequencing
data
to
construct
a
time-calibrated
consensus
this
group,
quantify
phylogenomic
discordance,
test
for
interspecies
introgression,
and
assess
patterns
genetic
diversity
demographic
history.
infer
that
radiation
started
Early
Pliocene
as
an
initial
speciation
burst,
followed
by
another
its
subgenus
Oncifelis
during
Pleistocene.
Our
findings
challenge
long-held
notion
ocelot
(Leopardus
pardalis)
margay
(L.
wiedii)
are
sister
species
instead
indicate
is
most
closely
related
enigmatic
Andean
cat
jacobita),
whose
reported
here
first
time.
In
addition,
we
found
newly
sampled
tiger
tigrinus
pardinoides)
population
from
Colombia
associates
with
Central
American
cats
oncilla).
Genealogical
discordance
was
largely
attributable
incomplete
lineage
sorting,
yet
augmented
strong
gene
flow
between
ancestral
branch
Oncifelis,
well
Geoffroy's
geoffroyi)
southern
guttulus).
Contrasting
trajectories
have
led
disparate
levels
current
genomic
diversity,
nearly
tenfold
difference
heterozygosity
ocelot,
spanning
entire
range
variability
extant
felids.
analyses
improved
our
understanding
history
felid
radiation,
highlight
benefits
inference
embracing
many
heterogeneous
signals
scattered
across
genome.
Genome Biology and Evolution,
Journal Year:
2022,
Volume and Issue:
14(10)
Published: Sept. 29, 2022
Abstract
A
male
mutation
bias
is
observed
across
vertebrates,
and,
where
data
are
available,
this
accompanied
by
increased
per-generation
rates
with
parental
age.
While
continuing
mitotic
cell
division
in
the
germline
post
puberty
has
been
proposed
as
major
cellular
mechanism
underlying
both
patterns,
little
direct
evidence
for
role
found.
Understanding
evolution
of
rate
among
species
requires
that
we
identify
molecular
mechanisms
change
between
species.
Here,
study
an
extended
pedigree
brown
(grizzly)
bear,
Ursus
arctos
horribilis.
Brown
bears
hibernate
one-third
year,
a
period
during
which
spermatogenesis
slows
or
stops
altogether.
The
reduction
predicted
to
lessen
and
lower
However,
using
whole-genome
sequencing,
find
highly
similar
expected
non-hibernating
We
also
carry
out
phylogenetic
comparison
substitution
along
lineage
leading
bear
panda
(a
species)
no
slowing
hibernator.
Our
results
contribute
accumulating
suggests
not
determinant
biases.
provide
quantitative
basis
improved
estimates
timing
carnivore
evolution.
Maintaining
germline
genome
integrity
is
essential
and
enormously
complex.
Although
many
proteins
are
involved
in
DNA
replication,
proofreading,
repair,
mutator
alleles
have
largely
eluded
detection
mammals.
replication
repair
often
recognize
sequence
motifs
or
excise
lesions
at
specific
nucleotides.
Thus,
we
might
expect
that
the
spectrum
of
de
novo
mutations
-
frequencies
C>T,
A>G,
etc.
will
differ
between
genomes
harbor
either
a
wild-type
allele.
Previously,
used
quantitative
trait
locus
mapping
to
discover
candidate
gene
Mutyh
increased
C>A
mutation
rate
family
inbred
mice
known
as
BXDs
(Sasani
et
al.,
2022,
Ashbrook
2021).
In
this
study
developed
new
method
detect
associated
with
variation
applied
it
data
from
BXDs.
We
discovered
an
additional
on
chromosome
6
overlaps
Ogg1,
glycosylase
same
base-excision
network
(David
2007).
Its
effect
depends
presence
allele
near
Mutyh,
both
loci
greater
numbers
than
those
alone.
Our
methods
for
analyzing
spectra
reveal
evidence
epistasis
may
be
applicable
humans
other
model
organisms.
Molecular Biology and Evolution,
Journal Year:
2023,
Volume and Issue:
40(10)
Published: Sept. 26, 2023
Abstract
Although
evolutionary
biologists
have
long
theorized
that
variation
in
DNA
repair
efficacy
might
explain
some
of
the
diversity
lifespan
and
cancer
incidence
across
species,
we
little
data
on
variability
normal
germline
mutagenesis
outside
humans.
Here,
shed
light
spectrum
etiology
mammals
by
quantifying
mutational
sequence
context
biases
using
polymorphism
from
thirteen
species
mice,
apes,
bears,
wolves,
cetaceans.
After
normalizing
mutation
for
reference
genome
accessibility
k-mer
content,
use
Mantel
test
to
deduce
divergence
is
highly
correlated
with
genetic
between
whereas
life
history
traits
like
reproductive
age
are
weaker
predictors
divergence.
Potential
bioinformatic
confounders
only
weakly
related
a
small
set
features.
We
find
clock-like
signatures
previously
inferred
human
cancers
cannot
phylogenetic
signal
exhibited
mammalian
spectrum,
despite
ability
these
fit
each
species’
3-mer
high
cosine
similarity.
In
contrast,
parental
aging
de
novo
appear
much
1-mer
spectrum's
combination
novel
signature.
posit
future
models
purporting
need
capture
fact
more
closely
similar
spectra;
model
fits
marginal
similarity
not
guaranteed
this
hierarchy
among
species.