'How microbes 'jeopardize' the modern synthesis" - review

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The assumptions of purely “chance” mutations that occur constantly, gradually, and uniformly in genomes have underpinned biology for almost a century but began as a “wait-and-see”–based acknowledgment by early evolutionary biologists that they did not know the chemical nature of genes or how mutations in genes might occur.

The chapter "Mutation" by Devon M. Fitzgerald and Susan M. Rosenberg in the series "How microbes 'jeopardize' the modern synthesis" discusses the role of mutation in microbial evolution and how it challenges the traditional view of the modern synthesis.


The modern synthesis is a unifying theory of biology that combines Darwin's theory of natural selection with Mendelian genetics and population genetics. It explains how evolution occurs by the process of natural selection, in which populations of organisms adapt to their environment over time by passing on favorable genes to their offspring.

Mutation is a change in the DNA sequence of an organism. Mutations can occur at random, due to errors in DNA replication or exposure to environmental factors such as radiation or chemicals. Most mutations are neutral, meaning that they have no effect on the organism's phenotype, or observable traits. However, some mutations can be beneficial, giving the organism an advantage in its environment. Other mutations can be harmful, causing diseases or other problems.

Fitzgerald and Rosenberg argue that mutation plays a more important role in microbial evolution than is generally recognized. They point out that microbes have very short generation times, meaning that they can evolve rapidly. They also have very high mutation rates, which means that they generate a lot of genetic variation. This combination of factors allows microbes to adapt to new environments very quickly.

Fitzgerald and Rosenberg also argue that mutation can lead to the emergence of new genes and new functions. This is because mutations can sometimes create new DNA sequences that were not present in the original genome. These new sequences can leading to new traits.

The role of mutation in microbial evolution is challenging the traditional view of the modern synthesis. The modern synthesis typically views random mutation as a source of genetic variation, but it does not emphasize the role of directed mutations in creating new genes and new functions. Fitzgerald and Rosenberg argue that this view is too simplistic and that mutation is a more important driving force of microbial evolution than is generally recognized.

Here are some specific examples of how directed mutations can jeopardize the modern synthesis:

  • Mutation can lead to the emergence of antibiotic resistance. Bacteria can rapidly evolve resistance to antibiotics through directed mutations. This is a major challenge for public health, as it makes it difficult to treat bacterial infections.

  • Mutation can lead to the emergence of new viruses. Viruses can also rapidly evolve through directed mutations. This is how new pandemics, such as the COVID-19 pandemic, can emerge.

  • Mutation can lead to the evolution of new species. Over time, directed mutations can lead to the accumulation of genetic differences between populations of organisms. This can eventually lead to the speciation, or formation of new species.

Overall, the chapter "Mutation" by Fitzgerald and Rosenberg provides a compelling argument for the importance of directed mutations in microbial evolution. The authors show that mutation can lead to a wide range of evolutionary changes, including the emergence of new genes, new functions, and new species. This challenges the traditional view of random mutations with the modern synthesis.

One of the key assumptions of the Modern Synthesis is that mutations are random and occur at a constant rate. This assumption is based on the idea that mutations are caused by errors in DNA replication or repair.

However, recent research has shown that mutations can also be induced by environmental stress. This means that mutations are not always random, but can be targeted to specific genes or genomic regions.

This is a challenge to the Modern Synthesis because it suggests that mutation rates can be affected by the environment. This could potentially lead to faster adaptation rates, especially in rapidly changing environments.

Another challenge to the Modern Synthesis is the observation that mutations can occur in clusters. This means that multiple mutations can occur in a small region of the genome at the same time. This could potentially lead to more complex and adaptive changes than would be possible with single mutations.

Overall, the discovery of stress-induced and clustered mutations suggests that mutation is a more dynamic and complex process than previously thought. This has implications for our understanding of evolution, and could lead to new ways to model and address cancer development, infectious disease, and evolution generally.

Here are some specific ways in which stress-induced mutation challenges the Modern Synthesis:

  • It suggests that mutation rates are not constant, but can be affected by the environment.

  • It suggests that mutations are not always random, but can be targeted to specific genes or genomic regions.

  • It suggests that mutations can occur in clusters, which could lead to more complex and adaptive changes.

These challenges suggest that the modern synthesis needs to be updated or replaced to reflect our new understanding of mutation.

Article Snippets:

Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by discoveries of molecular mechanisms of mutation in bacteria, now translated across the tree of life.

These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation.

Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution—the multiple changes needed to adapt protein functions and protein machines encoded by linked genes

Molecular mechanisms of stress-inducible mutation change ideas about evolution and suggest different ways to model and address cancer development, infectious disease, and evolution generally.

Though seemingly simple, ideas about mutation became entangled with the initially simplifying assumptions of both Darwin himself and the “Modern Synthesis”—the geneticists who embraced Darwin in the pre-DNA early 20th century, beginning evolutionary biology

Darwin considered generation of variation by chance to be a simplifying assumption, given that the origins of variation (and genes!) were unknown in his time, but he appears to have thought chance variation to be unlikely

“I have hitherto sometimes spoken as if the variations—so common and multiform in organic beings under domestication, and in a lesser degree in those in a state of nature—had been due to chance." - Darwin

This, of course, is a wholly incorrect expression, but it serves to acknowledge plainly our ignorance of the cause of particular variation

He also described multiple instances in which the degree and types of observable variation change in response to environmental exposures, thus seeming open to the possibility that the generation of variation might be environmentally responsive

However, even once mutations were described on a molecular level, many continued to treat spontaneous mutations as necessarily chance occurrences—typically as mistakes occurring during DNA replication or repair.

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