Gene Drive

Genome editing with the CRISPR-Cas9 system has worked successfully in a variety of animals, plants and microbes.

Researchers at the San Diego campus of the University of California have taken the process one remarkable step further. They created a plasmid that contains:

a CRISPR gene encoding a crRNA that binds to a gene (y) involved in Drosophila pigmentation.
a Cas9 gene that cuts the y gene. Disruption of this recessive X-linked gene produces yellow flies when the normal allele is absent.
flanking DNA sequences that enable the CRISPR-Cas9 genes to be physically incorporated into the y locus of a host X chromosome.

Expression of these genes produces more y-targeting crRNA and more Cas9. The result: the y locus on the second X chromosomes (in females) becomes inactivated as well. A heterozygous mutation has been converted into a homozygous mutation. The process is called gene drive or the mutagenic chain reaction.

One demonstration:

The females produced after injecting Drosophila embryos with the plasmid were mated with normal ("wild-type") males.

Normal Mendelian inheritance would have predicted that only the male offspring would have been yellow. The females would have inherited a normal y allele (black) from their fathers.

X	XX	XX
	X	X
Y	XY	XY

In fact, almost all (97%) of the flies, both sexes, were yellow. The mutant allele (red) inherited from their mothers converted the normal allele inherited from their fathers into the mutant form.

X	XX←X	XX←X
	X	X
Y	XY	XY

A second demonstration:

When mutant males were mated with wild-type females, Mendelian inheritance would predict that all the offspring would be normal.

X	XX	XX
	X	X
Y	XY	XY

In fact, while all the males were normal, all the females were yellow. The mutant allele inherited from their fathers converted the normal allele inherited from their mothers into the mutant form.

X	XX←X	XX←X
	X	X
Y	XY	XY

Implications of Gene Drive Technology

When a new mutant gene appears in a population, its frequency in that population may slowly increase (or decrease) if its phenotype confers a selective advantage (or disadvantage) on those carrying it (Natural Selection).

Even if there is there is no effect on survival, its frequency may very slowly increase or decrease by genetic drift.

But if the new allele has been engineered to trigger a mutagenic chain reaction, that allele will quickly sweep through the population turning all offspring into homozygotes expressing the allele.

Gene drive technology could have many beneficial effects.

For example, introducing a mutagenic chain reaction of a gene that blocks the ability of mosquitoes to transmit malaria could theoretically quickly end disease transmission.

However, like all technologies, gene drive poses risks as well. The ability to have an engineered gene sweep through a natural population raises the spectre of unexpected harmful consequences to entire ecosystems. For this reason, the workers in San Diego took elaborate precautions to be certain that their flies did not escape into the wild.

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1 December 2023