Gene Welding: Altering The Course of Evolution Through Selective Gene Insertions

With the aid of CRISPR-Cas9 technology, scientists are shifting the trajectories of the evolution of organisms. A researcher is now proposing that this human control of evolutionary course be called “genetic welding.”

Gene Drive Transmission

The makeup of a basic CRISPR-Cas9 synthetic gene drive element consists of the Cas9 gene and guide RNA (gRNA) sequence along with regulatory components to manage their expression (A). Other genes may also be included as genetic cargo to be integrated into the conversion process during homology-directed repair (HDR) that inserts the gene drive sequence into typical chromosome copies (B). Once the Cas9 initiates a double-stranded DNA break at the genomic location that the gRNA targets, the homology arm sequence on either side of the break matches the DNA flanking the gene drive sequence to call forth the HDR machinery. As a consequence of gene drive conversion, the gene drive allele can be passed on to as many as 100% of offspring (C), in contrast to the standard Mendelian inheritance of 50%, causing the synthetic gene drive to propagate throughout a population as individuals carrying the gene drive reproduce with those who don’t. Credit: Trends in Genetics

This suggestion was shared by Asher Cutter in a paper published recently in Trends in Genetics.

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However, the evolutionary geneticist also calls for the possible consequences of this technique to be considered. These need to be carefully examined, both ethically and scientifically, before genetic welding will be given the green light.

“Ethically, before humans apply this to natural populations, we need to start thinking about what the longer-term consequences might be on a time scale of hundreds or thousands of generations,” Cutter said.

The ability to rapidly alter the evolution of animals and plants via gene insertion is relatively recent. Therefore, the focus, for now, has mainly been on what occurs in the near term, not the long term.

About genetic welding

It was believed that the chances of genes being passed from parent to offspring are 50:50 (equal), according to classical Mendelian genetics.

A phenomenon referred to as “genetic drive” has been observed, however. Certain genes are capable of biasing their own spread, such that they are a lot more likely to be inherited by the offspring.

What Cutter calls genetic welding is the human-controlled version of this natural process. Scientists introduce genes that are believed to have an unfair heritability edge over others into natural populations.

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These genes spread seamlessly and swiftly through the populations they are introduced into. Therefore, they bring about faster evolutionary change than what obtains with natural and artificial selection.

This also means that genetic drive and genetic welding can keep up genes that may not really offer benefits to the organisms having them. As a result, the belief is that they could be useful for controlling harmful or disease-bearing species.

Genetic welding as a tool

Human control of evolutionary trajectory has been put forward as a tool for controlling invasive species and disease-bearing mosquito populations.

Another potential application is the genetic engineering of endangered species to enable them to better withstand infectious pathogens that threaten to wipe them out.

Genetic welding still has ethical concerns to surmount, however.

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“If ethicists, medical practitioners, and politicians decide that it is acceptable in some cases to edit the germ line of humans, then that would open the possibility that genetic welding could be used as a tool in that regard,” Cutter stated. “This would open a much bigger can of worms by virtue of the fact that genetic welding could change the entirety of a population or species, not just a few individuals that elected to have a procedure.”

It is difficult to assess the long-term effects of genetic welding experimentally. However, Cutter believed thought experiments, computer simulations, mathematical theory, and discussions with bioethicists could all help. Experiments involving short-living, rapidly-reproducing organisms could play a useful part as well.

References

Synthetic gene drives as an anthropogenic evolutionary force

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