A model organism used in laboratories for the past 100 years has evolved so extensively that it may no longer be fit for purpose, according to a new study “Laboratory strains of Escherichia coli K-12: things are seldom what they seem”, published in Microbial Genomics. E. coli K-12 has been repeatedly cultured and mutated, resulting in an organism that carries many genetic changes compared to the original isolated bacteria.

The research team, from Aston University, and the Universities of Birmingham and Nottingham, made their discovery after re-examining the early preserved samples and looking at the base sequence of their DNA. They found a large number of differences at the DNA sequence level, and the differences are bigger when they examined currently used stocks that derived from the original samples.

Dangerous limitations of one strain as a sole model

The work underscores the dangers of using one strain as a sole model, according to the scientists who add that it also confirms that bacterial sequences evolve over short time scales and provides a fascinating insight into the first baby steps of molecular microbiology.

“The past 10 years have seen a massive amount of bacterial genome sequencing and the picture that is emerging is that bacterial genomes change very fast,” says Doug Browning, PhD, of the School of Biosciences at Aston. “This was unimaginable 100 years ago, and, of course, this is why folk back then were quick to adopt the K-12 strain as the model for everything.”

The strain of bacteria in the study was originally isolated in 1922 from the feces of a recuperating diphtheria patient at Stanford University. The strain was preserved and over time it, and many derivatives, were distributed to research laboratories around the world for use by researchers looking to understand the workings of living cells at the molecular level.

“To understand more about this important model organism, we have sequenced the genomes of two ancestral K-12 strains, WG1 and EMG2, considered to be the progenitors of many key laboratory strains. Our analysis confirms that these strains still carry genetic elements such as bacteriophage lambda (λ) and the F plasmid, but also indicates that they have undergone extensive laboratory-based evolution,” write the investigators.

“Thus, scrutinizing the genomes of ancestral E. coli K-12 strains leads us to examine whether E. coli K-12 is a sufficiently robust model organism for 21st century microbiology.”

While the number of genetic variations which have appeared in the intervening decades may sound alarm bells in some research areas, for others it may represent new research opportunities.

“Actually, the diversity that all this generates can add a new dimension to our understanding,” points out co-author Steve Busby, PhD, of the Institute of Microbiology and Infection at the University of Birmingham. “It’s often true that things are seldom as they seem, and particularly so if you only study one strain.”

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