The Longest-Running Evolution Experiment
w4sLAQvEH-M • 2021-06-16
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Language: en
these are bacteria growing into
increasingly concentrated antibiotics
the bacteria stop growing when they hit
the first antibiotic strip
but then a mutant appears capable of
surviving in the antibiotic
then another mutation occurs and now the
bacteria can survive
10 times the concentration then
a hundred times and finally after just
11 days of evolution
these bacteria can survive antibiotics a
thousand times stronger than what would
have killed them at the
start you're watching evolution in
action
this video was sponsored by bounty
reminding you that a hygienic way to
clean up messes and spills
is with paper towel now bacteria are
everywhere
especially in damp places like
dishcloths so i'm going to do a little
experiment where i
add some fluorescent powder to this
dishcloth to represent bacteria without
telling anyone in my household
and then i'm going to come back later to
see where
all of this powder ends up but for now
i'm off to michigan to see the world's
longest running evolution experiment
let's go
this is richard lenski he started the
experiment 33 years ago
and along with a team of colleagues he
has kept it going
even on weekends ever since
in this lab are 12 flasks of live e coli
bacteria
they are the lucky few the ones that
have survived over three decades of
evolution in a lab
so there are 12 long term lines
in 1988 a single common ancestor spawned
these 12 separate populations
and ever since that day they have been
growing and dividing
independently so how have they evolved
there are other long-running evolution
experiments like since 1896
scientists at the university of illinois
have selectively bred corn
but they get only one generation per
year
whereas these bacteria go through six or
seven generations a day
so after 33 years the bacteria in these
flasks are generation
74 500. if those were human generations
it would represent 1.5 million years
of hominid evolution what we do to start
the experiment is we dilute a large
population of bacteria
onto a petri dish and each individual
cell makes a colony
and so then we take a little bit from
one colony to start one population a
little bit from another colony to start
another population
but effectively they all started from
individual
cells and that's important because it
means if we see the same thing
happening in replicate populations it's
not because
they started out with the same genetic
variants and natural selection just
fished out the same thing over and over
you actually had to have independent
mutations that would give rise to
these competitive advantages whatever it
might be that would
produce the repeatability across the the
12 replicate populations
the lab environment is very different
from the one the bacteria are used to
it's much simpler there are no other
organisms present
they're kept at 37 degrees celsius and
they live in the same solution
a mixture including glucose potassium
phosphate
citrate and a few other things their
only carbon source
is glucose which is limited above all
else
consuming that glucose and converting it
to offspring replicating as fast as
possible
has been essentially what we seem to be
selecting for
every day in each flask the bacteria
divide six or seven times
which increases their numbers a hundred
fold
normally we think of generations as
being limited by the time that has
elapsed
but in the case of these bacteria
they're limited by the resources
available to them
if they had 10 times the solution they
would increase their numbers an
additional 10 times
then almost every day for the past 33
years
this transfer process has taken place
0.1 milliliters or 1 percent of the
solution from each flask
is transferred to a sterile new flask
containing the same solution
it essentially dilutes the bacteria a
hundred fold
this gives them the space and resources
they need to grow and divide again
increasing their population a hundred
times before
this same process is repeated the next
day
and then the day after that and the day
after that even
on weekends this process has been going
on for over
three decades what happens to bacteria
that are
not transferred to the new flasks the 99
percent
that's the autoclave room what happens
in the autoclave room
every day 99 of the e coli meet their
demise in this horrible
room is this like a bacterial
crematorium yeah yeah exactly
you can imagine if the scientists didn't
do this but instead gave all the
bacteria a hundred times more solution
to grow on every day
well the experiment would soon become
unmanageable on day two you would need
a cubic meter of solution but by day 13
the experiment would be 10 times the
volume of earth
and by day 42 the experiment would fill
up the entire
observable universe to me it seems like
the whole idea of genetics
is for them to stay constant and for
mutations to be rare
yes yet in your experiment it seems
they're not rare
so we estimate that in our bacteria
only about one out of maybe a hundred or
one out of a thousand
cells will have even a single mutation
so
that's not very much by contrast in
humans it's estimated that each one of
our offspring has perhaps
10 20 50 new mutations so the bacteria
are extremely conservative but there are
also billions of them
in even a tiny flask and so if you have
a chance in a thousand of mutating and
you have a billion individuals
then every day in one of these flasks we
might have a million
new mutations so that's a lot of
variation on which natural selection can
act
maybe half of those mutations have no
effect whatsoever
on the bacteria's ability to grow and
thrive in that particular environment
they might be mutations that would
matter out in the great outdoors but
this is a very simple environment maybe
those genes aren't even expressed
another half of the mutation speaking
very very roughly might actually be
deleterious mutations they make the
bacteria
an inferior competitor but there's maybe
out of
those million mutations that occur every
day
maybe there's 10 maybe there's 100 maybe
there's a thousand of them that actually
change something in the cell that gives
the bacteria a competitive advantage
over their progenitors
and those then grow over the course of
that day then
every day 99 percent of the population
is eliminated
this lucky one percent prevails and if
those lucky one percent include one of
the guys from the previous day that was
growing
at 10 faster than the other guys it has
a higher probability of contributing
to that next flask the next day's flask
and in the fresh medium and it will
continue to grow faster
at a ten percent clip and that compounds
by an exponential process
so the mutations you know are really
rare when they first occur and many of
them are lost
but once they get common if they have
that competitive advantage
they'll just sweep through the
population but
how do you know that the bacteria
actually have a competitive advantage
i mean how can you tell that they're
getting better suited to their
environment
well this is where one of the unique
properties of bacteria come in
they can be frozen for long periods of
time and then
revived and so they're stored in
suspended animation here
so these are the racks that contain the
frozen samples of the
bacteria from the various generations
every 500 generations roughly 75 days
they freeze a sample of each population
by freezing previous generations lenski
and his team have a frozen
fossil record so our samples from over
30 years ago
remain perfectly viable and so that
gives us an ability to do what i like to
call time travel
we can literally compare organisms that
lived at different points
in time so we can compete bacteria from
generation 70 000
against their ancestor that's right
the way they measure fitness is by
competing the current generation of
bacteria
against older generations it's like a
strange bacteria fight club
they thaw out the old generation mix it
into a flask with the current generation
and then played out a sample of the
solution to see the relative abundances
of the two populations at the start
then they incubate the flask for a day
and then plate them out again
and the point is to compare their
relative growth rates
which generation was better able to
utilize the glucose
and divide faster well how the heck do
you tell an evolved bacterium from its
ancestor
do they say wave little flags at you and
say hey i'm the evolved guy
and of course they don't but what we
have is this color
marker in the embedded in the experiment
so six of our populations on a certain
kind of agar plate make red colonies and
six of them
make white colonies and we have one of
version of the ancestor that makes red
colonies
and one that makes white colonies we can
compete
one of the red evolved populations
against the white ancestor
or one of the white evolved populations
against the red ancestor
and we can distinguish them in this case
it's clear that the evolved red
population
outcompeted their white ancestor now to
determine the winner
all of the colonies are counted by hand
so what was the earliest sort of big
findings from the experiment
the first thing we found not that there
was any doubt about
it but it's one of the most direct
demonstrations of darwinian adaptation
by natural selection you can imagine
yes they're getting to be better
competitors over time
it's a common observation in other
evolution experiments that evolution in
a new environment gets
off to a rip-roaring start and then
tends to slow down over time
and so we repeated that observation and
i imagined that
the long-term lines would actually sort
of flatline at some point
and i actually thought about stopping
the experiment but i got wise advice
from colleagues and from my wife
madeline
let's keep it going and so i agreed to
that and it's a good thing he did
because in 2003 the bacteria started
doing something
remarkable one of the 12 lineages
suddenly began to consume a second
carbon source
citrate which had been present in our
medium
throughout the experiment it's in the
medium as what's called a chelating
agent to bind
metals in the medium but e coli going
back to its original definition as a
species is incapable of that
but one day we found one of our flasks
had more turbidity
i thought we probably had a contaminant
in there some bacterium had gotten in
there that could eat the citrate
and therefore had had raised the
turbidity we went back into the freezer
and restarted evolution
we also started checking those bacteria
to see whether they really were e coli
yep they were e coli
were they really e coli that had come
from the ancestral strain yep
so we started doing genetics on it it
was very clear that one of our bacteria
lineages had essentially i like to say
sort of woken up
one day eaten the glucose and unlike any
of the other lineages discovered that
there was this nice
lemony dessert and they begun consuming
that and getting a second source
of carbon and energy zach was interested
in the question of
why did it take so long to evolve this
and why has only one population evolved
that ability
he went into the freezer and he picked
bacterial individuals or clones
from that lineage that eventually
evolved that ability
and then he tried to evolve that ability
again
starting from different points so in a
sense it's almost like well it's like
rewinding the tape
and starting let's go back to the minute
five of the movie let's go back to
minute 10 of the movie minute 20 of the
movie
and see if the result changes depending
on when we did it
because this citrate phenotype there
were essentially two competing
explanations for why
it was so difficult to involve evolve
one was that it was just a really rare
mutation
it wasn't like one of these just change
one letter it was something where
maybe you had to flip a certain segment
of dna and you had to have exactly this
break point and exactly that break point
and that was the only way to do it so it
was a rare event
but it could have happened at any point
in time the alternative hypothesis
is that well what happened
was a series of events that made
something perfectly ordinary
become possible that wasn't possible at
the beginning
because a mutation would only have this
effect
once other aspects of the organism had
changed
to make a long story short it turns out
it's such a difficult trait to evolve
because both of those hypotheses are
true
the experiment uncovered other
surprising findings
like instead of the bacteria getting
more numerous over time
they actually decreased in number but
each individual bacterium got larger
six of the twelve populations evolved
hypermutability
mutation rates a hundred times higher
than their ancestors
but these populations subsequently
acquired additional mutations that
brought the mutation rate back down
i mean it's advantageous to be able to
evolve faster than others but
if the mutation rate is too high then
offspring have too many
deleterious mutations but maybe the most
surprising finding of all
is what didn't happen this view i had
that they were flatlining turned out to
be quite false
i had sort of imagined a very simple
mathematical model
you can create something called a
rectangular hyperbola i guess
which has a initial high slope and then
reaches an asymptote
but they're equally simple models
there's a model that also has just two
parameters called a power
law model that says things slow down
but it doesn't have an upper bound it
says just keep going for time immemorial
and things will just keep going faster
but a slower and slower rate
of further improvement and it turned out
that model
actually fits our data better than that
original model i had imagined and not
only does it fit it better
okay you say statistics science you know
fitting curves it actually predicts the
future and that's what's really cool
because the original model if you give
it say just
5 000 generations worth of our fitness
data and ask it to predict into the
future
it says the asymptote is here but then
when we get more data
no the bacteria are up here they've
passed that asymptote
whereas this power law model which says
things are slowing down but never
reaching an asymptote
we give it just one tenth of our data
from the past
and it projects very accurately out to
fifty thousand and even sixty thousand
generations when we last
looked it predicts sort of the future
course of the evolutionary trajectory
and to me that's kind of profound and it
sort of changed
the way i look at this experiment and
even a little bit how i look
at life on earth i mean life on earth
doesn't stop evolving we know that and
we know that but we think that's oh
that's because they're asteroid impacts
that's because of human impacts
that's because they're viruses that are
attacking their hosts and that
the co-evolution is causing evoluti is
causing evolution to never stop
the world is always changing so of
course evolution never stops
and that is a hundred percent true but
what our
experiment suggests is that even in the
absence of environmental change
there are so many opportunities of
smaller and smaller magnitude to
continue to make
progress that in fact progress
probably would never stop even in a
constant environment
to me it's one of the reasons to keep
this experiment going does this model
continue to predict
the unfolding of the future fitness
trajectory
okay now the conclusion of the
experiment where i
look for that fluorescent powder using
this uv torch
so let's hit the lights
whoa there is a lot of fluorescent
powder around here
obviously there's a lot in the sink uh
but also here
on the tap looks like someone wiped down
the handle
and the faucet oh check out the
dishwasher
yeah and on the handle this is a great
way of visualizing how dishcloths can
spread bacteria around the house
what
looks like finger marks
as a dad i encounter lots of big messes
and sticky hands and slimy faces
so when there is a mess or spill in my
kitchen i choose to clean it up with
bounty
so i want to thank bounty for sponsoring
this video and i want to thank you
for watching
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