Understanding Evolution

A "new mode" of evolution?

February 2020

A scanning electron micrograph (SEM) of a number of Pseudomonas aeruginosa bacteria

An image of Cryptococcus neoformans, courtesy of Wikimedia

In the age of clickbait, headlines are best consumed with more than a grain of salt. Is Thailand really in for a "Viral Rampage!" of the new coronavirus?  Is Kim Jong-un's aunt actually "Back from the Dead?"  Did the United States literally cut a deal with killer pirates?  Possibly...but more often than not, the truth is less sensational. So when a science news site exclaims over the "new mode of evolution" recently uncovered by scientists (as the website LiveScience did last month), it's worth digging deeper...

Where's the evolution?

The headline in question describes research on the DNA of the yeast Cryptococcus neoformans, which can cause deadly infections of the lungs and other organs in patients with suppressed immune function. To understand the new research, first you need a little background on methyl groups — a sort of chemical decoration that sticks to the outside of the DNA molecule. The DNA of many species, including that of humans and C. neoformans, is studded by methyl groups.  While methyl groups do not affect the DNA's genetic sequence, they do affect its function. They help determine which genes in the underlying DNA are turned on and off. Methyl groups also help keep in check rogue bits of DNA, called transposons. Transposons can be "copied and pasted" around the genome, interrupting critical genes and wreaking havoc on the detailed instructions encoded by the genome. Methyl groups help keep these disruptors turned off and the genome functioning as it evolved to. All of this means that the placement of methyl groups along the genome can influence what an organism looks like, how it acts, how its physiology functions — potentially impacting all aspects of its phenotype.

Methyl groups are added to DNA through two distinct processes.  First, by being attached in a new position: a specialized protein may stick a methyl group onto a naked bit of DNA.  And second through inheritance: when a piece of DNA is copied to make a new cell or a new organism, a different specialized protein copies the patterns of methylation from the original DNA strand onto the new DNA strand. In this way, patterns of methylation are passed on from parent to offspring, just as DNA sequences are. 

However, the new research determined that C. neoformans is missing the protein that sticks methyl groups onto DNA in a new position and only has the protein that copies methylation patterns from one DNA strand to another. This yeast's close relatives have both proteins, so the scientists reasoned that C. neoformans' ancestors must have had both too and lost one during its subsequent evolution. But that left a mystery. How did the yeast keep its methylation patterns over evolutionary timescales? 

Copying methylation patterns is a buggy process; copies are not always perfect replicas. The protein that sticks methyl groups onto new positions can solve that problem by filling in a methyl group when the copying machinery breaks down and leaves one off. But C. neoformans has no fixer protein.  Without a repair mechanism, we'd expect so many methyl copying errors to occur over long periods of time that C. neoformans' genome would be completely methyl-free today.  But it isn't! 

After examining multiple lines of evidence, the researchers concluded that the most likely explanation is a form of natural selection: yeast with more accurate methylation copies are better able to survive and reproduce (i.e., are more evolutionarily fit) than yeast with buggy methylation copies and missing methyls. Thus, yeast with accurate methylation copies become more frequent in the population and yeast with lots of missing methyls are weeded out. While it's hard to know for sure what advantage yeast with accurate methylation copies have, it likely has to do with the protection methyl groups provide from the destructive effects of transposons. This is the "new mode" of evolution from the headline.

While the discovery of natural selection operating to maintain methyl patterns is very cool, it's really just another version of natural selection.  Natural selection operates on a system when it has four features (with the handy acronym VIST):

  • Variation - For example, in a classic example of evolution by natural selection, the peppered moths, variation exists because some moths have dark wings and some have lighter wings.  In C. neoformans, some yeast have more accurate methylation pattern copies, and some have less accurate.
  • Inheritance - For example, in the peppered moth, wing color is passed down from parent to offspring because this trait is encoded by DNA.  In C. neoformans, methylation patterns are passed down from parent to offspring by a copying mechanism that involves a special protein. This is known as epigenetic inheritance - inheritance that does not involve passing along changes in DNA sequence.
  • Selection - For example, in the peppered moth, when tree bark is darkened by soot, moths with dark wings are more likely to avoid being eaten and survive to reproduce. In C. neoformans, yeast with accurate methylation pattern copies seem to be protected from damaging transposons and so more successfully reproduce.
  • Time - In both the peppered moth and C. neoformans, variation, inheritance, and selection are present from one generation to the next, allowing evolution by natural selection to occur over time.

We already know about plenty of other versions of natural selection.  For example, when the selection step of VIST involves not the differential ability to survive and reproduce in the wild, but instead a human selecting which individuals get to reproduce, we have artificial selection, a process that humans have used for millennia to form new varieties of plants and breeds of animals. Scientists have built computer programs and robots that randomly vary and are copied, instantiating natural selection in completely non-biological systems.  We've even studied the evolution of languages and artifacts, in which inheritance occurs through learning and culture, not through any particular molecule.

VIST is just a basic recipe for natural selection, like a basic recipe for meatballs.  You need some ground meat, some spices, and binder like bread crumbs and eggs.  Whether you use turkey or lamb, black pepper or cumin, bread crumbs or cracker crumbs...you are still going to come out with a meatball.  And whether inheritance in VIST happens through DNA sequences or epigenetic inheritance, as in the case of C. neoformans, you are still going to come out with evolution by natural selection.  This isn't a brand new mode of evolution.  This is the same mode of evolution described by Darwin and Wallace more than 150 years ago — and now researchers are tasked with studying a newly discovered variation on the familiar theme.

Primary literature

  • Catania, S., Dumesic, P. A., Pimentel, H., Nasif, A., Stoddard, C. I., Burke, J. E., ... Madhani, H. D. (2020). Evolutionary persistence of DNA methylation for millions of years after ancient loss of a de novo methyltransferase. Cell. 180: 263-277. read it

Discussion and extension questions

  1. What is meant by the phenotype of an organism? How can changes in DNA sequence affect this phenotype? How can changes in methylation affect this phenotype? 
  2. Describe the fitness benefit that methylation seems to provide C. neoformans.
  3. Researchers discovered that C. neoformans is missing a protein that attaches new methyl groups to parts of DNA that lack them.  Why was this surprising?
  4. Use the elements of VIST to explain in your own words how and why C. neoformans has a methylated genome today.
  5. Advanced: Humans and many other species have methylated DNA and likely also benefit from its transposon-suppressing powers. Do you think it likely that the sort of epigenetic natural selection described in C. neoformans is occurring in most of these other species as well? Explain your reasoning.
  6. Advanced: All the available evidence suggests that mutations (the ultimate source of genetic variation in DNA) occur randomly with respect what changes might benefit the organism in a particular environment. However, imagine for a moment that scientists discovered a new cellular system that produces mutations in a non-random fashion, biasing changes towards those that would help the organism. What aspect of VIST would this new source of mutations be relevant to? Would it constitute a new mode of evolution?  Would it mean that the theory of evolution is false? Explain your reasoning.


  • Catania, S., Dumesic, P. A., Pimentel, H., Nasif, A., Stoddard, C. I., Burke, J. E., … Madhani, H. D. (2020). Evolutionary persistence of DNA methylation for millions of years after ancient loss of a de novo methyltransferase. Cell. 180: 263-277. 


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