A Vivid Demonstration of Bacteria Adapting to Antibiotics via Mutations and Selection

The fact that bacteria are able to develop resistance to antibiotics has been a textbook example of evolutionary processes in action.  Mutations and natural selection—two primary agents of change—work together to sculpt new genetic combinations allowing individuals to exploit resources unavailable to bacteria previously unable to resist antibiotic chemicals in their environment.   Now you can watch a powerful illustration of E. coli  undergoing evolution of antibiotic resistance in a video produced by scientists at the Harvard Medical School.  The video below shows a fascinating new way to watch bacterial strains evolve and then examine the mechanisms of the adaptive process in detail.

What have you witnessed?  This video is just 2 minutes long but provides a good overview of research just published in the journal Science (see reference below).  At a minimum you are seeing the origin of new gene variations—alleles—via mutations and natural selection acting on the phenotypes—the physical manifestations—of those mutations.

The initial colony of bacteria introduced onto the edges of the huge petri plate lacked the ability to resist antibiotics.  They were able to survive in the agar at the ends which had no antibiotic but in the next “lane” of agar there was enough antibiotic to kill the bacteria.  Any bacteria in the initial population that experienced a genetic change that allowed it to survive in the second lane could free themselves – at least for a while – from the competition for diminishing resources in the first lane and find themselves in a resource rich region with fewer competitors.  Hence, evolving the ability to resist the antibiotic would be a favorable change for these bacteria.

Each time a bacteria divides it must copy its genome but in doing so they always make some mistakes—mutations. After a day or two, billions of bacteria have colonized the outer lanes of the large petri dish. Collectively, those bacteria have experienced billions of mutations.  Most of those mutations would have been negative (either lethal or reduced their efficiency in some way) or neutral and therefore had little effect on the success of the bacteria.  Some may have helped the E. coli compete better for the limited resources in the first lane.   Of the billions of mutations only a few occurred in genes that provided some individual bacteria the ability to survive in the presence of the small amount of antibiotic in the second lane.  Those bacteria were free to move into the second lane and begin to take advantage of the resources available there.  As this new colony grew into the second lane the colonies would have continued to accumulate more mutations.  Again, most were negative or neutral but some of those mutations conferred even greater capacity of the bacteria to resist antibiotics allowing those bacteria to move into the third lane.

This same pattern of continued mutations and natural selection continues allowing mutations that provided greater ability to resist antibiotics to accumulate thus allowing additional area with more resources to be invaded.

Mutations are random but natural selection is not.

What is really cool is that not only can you see which lineages of bacteria had mutations that conferred a greater ability to resist antibiotics but because each bacterial lineage can be traced the researches could sample the bacteria in those lineages.  They subsequently extracted the genomes of those bacteria and sequenced them to reveal their entire code.  By examining of the complete genomes of ancestors and descendants, they located every change (mutation) in them.  By characterizing when and where those mutations occurred in the genome they could identify the chronological order of those mutations and therefore recreate the steps the bacteria used to gain resistant to the antibiotic.

You can see from the video that multiple lineages of bacteria from both sides were able to generate adaptations to every increasing antibiotic concentrations but the interesting question is, did they come up with the same solutions to the antibiotic problem?  The answer is, no!  They found unique ways of solving the same problem.  Natural selection is a process that seeks to solve a problem for the organism but the solutions it finds are limited to the available pool of variations from which it can choose. Those variations are usually generated randomly by mutations.

So the mutations were random with respect to locations in the genome but whatever mutations did occur were then sorted by natural selection eventually resulting in new functions.  Interestingly, the bacteria that finally conquered the 1000x dose of antibiotic were able to do so not because of a single large change in its genome but as a result of many small steps that added up to high resistance.  By introducing the bacteria to a gradually changing environment – from low concentration to higher and higher concentrations – the bacteria were able to take advantage of multiple mutations to make small adaptations along the gradient.  The Harvard scientists tested the ability of the bacteria to make the jump directly to high concentrations of antibiotic and that experiment failed to generate resistant bacteria.   This showed that the ability to resist high loads of antibiotic required a genetic apparatus that was too complex to originate by a single mutation.

The same thing happens in nature. As long as a population is not thrown into a radically new environment some individuals will have new variations of genes resulting from mutations that will allow them to survive in that new environment after which they can further adjust to the new conditions through additional mutations. However, large-scale changes, such as snakes being introduced onto an island that has many flightless birds who lay their eggs in nests on the ground will result in the extinction of the birds because they are unable to adapt quickly enough to such a dramatic change.

But are we witnessing evolution?

We certainly are witnessing a genetic change in this population of E. coli and thus witnessing biological evolution in action.   We are witnessing descent with modification.  Young earth creationists will respond that this study is much ado about nothing.   This is only demonstrating adaptation and not evolution.  After all, this isn’t evolution because the bacteria didn’t change from one kind to another which is what they think must happen to meet their definition of evolution.  I expect that they will claim that no new information was created by these changes but rather that the ability to resist antibiotics requires the loss of some other ability and therefore doesn’t constitute real advancement.

The latter would not be an accurate statement though the former is correct: we have not witnessed one species of bacteria becoming something completely different.  But this demonstration never claimed to witness the entire process of macroevolution – the origin of new species – but rather allows a powerful witness and test of evolutionary mechanisms that can lead to new species formation. This new research apparatus provided a new way to ask and answer many questions about how adaptation occurs.  For example:

Can organisms adapt to new environments? Yes.  Nothing new here but the video clearly shows bacteria adapting to an environment in which the ancestral lineages were not able to survive.

Can natural selection act on mutations that improve the fitness of individuals in populations?  Yes!  Only a couple of the billions and billions of bacteria that experienced mutations had mutations that were useful in that new environment and yet that new environment was able to select those individuals and allow them to colonize that environment.

If the vast majority of mutations are lethal, somewhat deleterious or have no effect doesn’t that mean that mutations are destroying species over time rather than helping to form new ones?  No. This is evident in this experiment.  From the time that a few bacteria became billions as they grew in the non-antibiotic zone there would have been billions of individual mutations among them.  Most of those were likely neutral and therefore had no effect but millions were probably lethal or severely impaired the bacteria.  Those bacteria simply did not continue to divide leaving other bacteria with neutral and positive mutations in that environment to perpetuate the colony.  So natural selection is sorting out millions of negative mutations in addition to selecting for positive mutations in the new environment.  It is these new mutations, however rare they may be, that yield adaptation to new or changing environments that result in real changes to a species over time.

Can mutations produce new interactions among genes?  Yes. Direct sequencing of ancestors and descendants which is what this experiment allows and why it is so powerful – beyond the visual aspect – shows that mutations in genes cause them to work together in new ways to produce resistance to the antibiotic.

Do all independent lineages of bacteria that gain antibiotic resistance use the same combinations of mutations to achieve that resistance?  No, but they did share some mutations in common demonstrating that natural selection under the same conditions will recognize identical mutations when they occur and select the individuals with those mutations. In other words, natural selection is far from random but rather the arbiter of the value of any mutation.

Do bacteria that become more resistant to antibiotics compensate for that increased ability by losing other abilities?  In most cases yes, but in several cases, compensating mutations occurred later in the same lineages that allowed them to gain back all their previous functions making them truly more adapted to the new environment than any of their ancestors.

All of these results demonstrate what was already known about how bacteria may evolve but this experiment helps tease apart the role of mutations and natural selection in new ways. What this experiment so elegantly demonstrates is that new environments cause the sorting of millions of variations in genomes all caused by random mutations when cells copy themselves such that new variations that confer some advantage are preserved in descendant lineages that take advantage of those new environments.  This is natural selection in action.  This is descent with modification.  This is the process of evolution being played out on a small temporal and physical scale.

This new method of observing and testing evolutionary mechanisms has similarities to Dr. Rich Lenski’s work with bacterial evolution.  Lenski’s lab has evolved bacteria under the same conditions for over 60,000 generations and documented mutations through that time to show how the bacteria become more fit for their environment and in some cases show that some lineages of bacteria have gained the ability to utilize resources unavailable to the ancestral bacteria.  I expect that like Dr. Lenki’s work this new experimental apparatus will provide many new insights as it allows many evolutionary mechanisms to be tested. I am sure that we will be seeing many more videos like the one above in the future.

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