Horizontal gene transfer: transfer controls (Introduction)

by David Turell , Tuesday, August 06, 2019, 20:27 (1717 days ago) @ David Turell

Horizontal gene transfer in bacteria is necessary for bacteria to evolve and add new functions. It is under highly complex controls, not yet fully understood:

https://phys.org/news/2019-08-block-unwanted-genetic.html

"Random mutations add some diversity, but there's a much faster way for bacteria to reshuffle their genes and confer evolutionary advantages like antibiotic resistance or pathogenicity.

"Known as horizontal gene transfer, this process permits bacteria to pass pieces of DNA to their peers, in some cases allowing those genes to be integrated into the recipient's genome and passed down to the next generation.

"The Grossman lab in the MIT Department of Biology studies one class of mobile DNA, known as integrative and conjugative elements (ICEs). While ICEs contain genes that can be beneficial to the recipient bacterium, there's also a catch—receiving a duplicate copy of an ICE is wasteful, and possibly lethal. The biologists recently uncovered a new system by which one particular ICE, ICEBs1, blocks a donor bacterium from delivering a second, potentially deadly copy.

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"Although plasmids are perhaps the best-known mediators of horizontal transfer, ICEs not only outnumber plasmids in most bacterial species, they also come with their own tools to exit the donor, enter the recipient, and integrate themselves into the recipient's chromosome. Once the donor bacterium makes contact with the recipient, the machinery encoded by the ICE can pump the ICE DNA from one cell to the other through a tiny channel.

"For horizontal transfer to proceed, there are physical barriers to overcome, especially in so-called Gram-positive bacteria, which boast thicker cell walls than their Gram-negative counterparts, despite being less widely studied. According to Davis, the transfer machinery essentially has to "punch a hole" through the recipient cell.

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"Sure, ICEs are "selfish bits of DNA" that persist by spreading themselves as widely as possible, but in order to do so they must not interfere with their host cell's ability to survive. As Avello explains, ICEs can't just disseminate their DNA "without certain checks and balances."

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"In this most recent study, they've identified the mysterious blocking mechanism as a type of "entry exclusion," whereby the ICE in the recipient cell encodes molecular machinery that physically prevents the second copy from breaching the cell wall. Scientists had observed other mobile genetic elements capable of exclusion, but this was the first time anyone had witnessed this phenomenon for an ICE from Gram-positive bacteria, according to Avello.

"The Grossman lab determined that this exclusion mechanism comes down to two key proteins. Avello identified the first protein, YddJ, expressed by the ICEBs1 in the recipient bacterium, forming a "protective coating" on the outside of the cell and blocking a second ICE from entering.

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"Cell-cell signaling allows a cell to spread the word to its neighbors that it already has a copy of ICEBs1, so there's no need to bother assembling the transfer machinery. If this fails, exclusion kicks in to physically block the transfer machinery from penetrating the recipient cell. If that proves unsuccessful and the second copy enters the recipient, immunity will initiate and prevent the second copy from being integrated into the recipient's chromosome.

"'Each mechanism acts at a different step, because none of them alone are 100 percent effective," Grossman says. "That's why it's helpful to have multiple mechanisms."
They don't know all the details of this transfer machinery just yet, he adds, but they do know that YddJ and ConG are key players.

"'This initial description of the ICEBs1 exclusion system represents the first report that provides mechanistic insights into exclusion in Gram-positive bacteria, and one of only a few mechanistic studies of exclusion in any conjugation system," says Gary Dunny, a professor of microbiology and immunology at the University of Minnesota who was not involved in the study.
"This work is significant medically because ICEs can carry "cargo" genes such as those conferring antibiotic resistance, and also of importance to our basic understanding of horizontal gene transfer systems and how they evolve.'"

Comment: This complex transfer system with precise controls cannot develop stepwise by chance. It must be designed and created all at once as an initial step.