Accelerated Evolution, Microbial Style

Jeff F. Miller, PhD

The President’s Forum at the 2018 ASM Microbe meeting opened the eyes of many in the audience to the capacity of microorganisms to evolve. Far from drifting along in the evolutionary pool, with the occasional acquisition of a gene that better equips the microbe for survival, prokaryotes and Archaea, and the viruses that they contain, possess molecular machinery that can speed up evolution and generate astonishing genetic diversity.

The person at the epicenter of this research was the speaker, Jeff F. Miller, PhD, Director of the California Nanosystems Institute and a faculty member of the Department of Microbiology and Immunology, University of California at Los Angeles.

As described by Dr. Miller, the main player is a retroelement, a genetic construct that contains the enzyme reverse transcriptase. Reverse transcriptase catalyzes the creation of DNA from RNA. The DNA can subsequently move into the host genome. For those old enough to remember, the process is analogous to splicing bits of movie film into the existing reel of film. At the movie theater, the result when the film is played can be a new scene in the movie. In the microbial world, the result is a new genetic landscape, as a new stretch of DNA can be used to encode new information.

Retroelements don’t just insert at 1 site on a genome. They can insert at multiple sites and can excise and reinsert somewhere else. The insertion at various regions of the host genome can generate new genetic sequences and new versions of proteins that will differ slightly or markedly from the original. The process can be repeated over and over, even within the same cell, giving microbes an almost unlimited array of variations. If the revised version yields a benefit to the microbe, it will likely be retained and passed on to subsequent generations. The result is accelerated evolution.

For Miller, the story began in 2002, when a graduate student in his lab discovered a bacteriophage for Bordetella bronchiseptica, which is closely related to the bacterium that causes pertussis. The BPP-1 bacteriophage latches onto the surface of the bacteria via a protein dubbed Mtd, which is located at the tip of the tail fibers of the phage. The first-ever finding of reverse transcriptase in the bacteriophage sent the researchers on a new path that culminated in the demonstration of what they termed diversity-generating retroelements, or DGRs for short.

“DGRs are a remarkable class of retroelements that have evolved useful functions to benefit their hosts. They use their reverse transcription activity to introduce a vast number of sequence variants into defined sites of specific target protein genes. The enormous number of protein variants allows the host to adapt rapidly to changing environmental conditions,” said Dr. Miller.

The DGR of the BPP-1 bacteriophage comprises the mtd gene that has a variable region, the gene for reverse transcriptase, a region called the template repeat, and a final region termed an accessory variability determinant. The reverse transcription involves the template repeat, with the DNA that is produced being transferred to the variable repeat. The template repeat contains almost 2 dozen sequences that can direct the changes in the variable repeat region, which creates the possibility of a staggering number of alterations in the Mtd protein.

There are a lot of other complex details of the process; but, the upshot is that the system has the potential for a huge diversity in the protein structures that can result. Differences in protein structure often translate to functional differences, ranging from very minor to major.

In Legionella pneumophila, as an example, the surface protein that is affected theoretically has 10¹⁹ variations. Another bacterium, Treponema denticola, has 10²⁰ theoretical variants in the target protein, TvpA.

A ton of research over the past decade has made clear that DGRs are not some quirky curiosity. Rather, DGRs are a feature of thousands of species of prokaryotes as well as Archaea.

Recent research by Dr. Miller and colleagues has indicated that in Bacteroides bacteria, DGRs are influential in the surface appendages termed pili. The resulting redesign of the tip of an individual pilus could alter the interactions the bacteria are capable of, with the possibility of the sharing of genetic information that might otherwise have not occurred so readily. This could result in what is termed horizontal transfer, with information being passed from 1 living microbe to another in real-time, in contrast to the inheritance of information described above that is passed from 1 generation to succeeding generations. Horizontal transfer can spread information much more rapidly.

It is now clear that DGRs are fundamentally important in the ability of microorganisms to make their living. And, in a practical sense, the ability to engineer DGRs to home in on a variety of different genes may have value in bioengineering of novel proteins.

Dr. Miller served as President of ASM from 2012-2014. He was elected to membership in the National Academy of Sciences in April 2015.

Headshot Source: UCLA BioScience website: bioscience.ucla.edu/faculty/jeff-f-miller.

DISCLOSURES

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PRESENTATIONS

President’s Forum

Accelerated Evolution by Diversity-generating Retroelements in Phage, Microbes, and Microbiomes. Jeff F. Miller, PhD, California Nanosystems Institute and Department of Microbiology and Immunology, University of California at Los Angeles.

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com