Driving Out Malaria

HOW GENE DRIVES SPREAD
HOW GENE DRIVE WORKS
Introduced endonuclease gene (aka the gene drive)
Recognition site
Homologous
chromosomes
Without gene drive, an allele will be passed from generation to generation via traditional Mendelian genetics. That is, when a heterozygous
individual carrying only one copy of the allele mates with an individual lacking it altogether, only half of their offspring will inherit the
genetic segment. But in a gene drive that spreads the allele to the homologous chromosome in the germline, all progeny will receive a copy.
With gene drive, it’s even possible for a deleterious allele to spread though the population, despite imposing a severe fitness cost.
With
genetic
modification
WITHOUT GENE DRIVE
Wild Type
For years, researchers have looked to
genetically modify mosquitoes to prevent
the spread of malaria. But while introducing
genetic changes has long been supported
by advancing technologies, getting those
modifications to spread through wild
mosquito populations has remained a
challenge. Now, the newly understood
concept of gene drive, in which genetic
elements can spread more rapidly than those
following traditional Mendelian inheritance
principles, may finally solve the problem.
1.0
Frequency
Homing endonuclease recognizes and cuts a target sequence in the wild-type chromosome
that is identical to the insertion site for its gene in the homologous chromosome.
0.5
0.0
0
10
20
30
Generations
If the genetic modification has no negative
fitness consequences, its frequency in the
population will remain at whatever the
initial introduced frequency was.
The cell’s DNA repair machinery then uses the engineered chromosome of the homologous pair,
which contains the endonuclease gene, as a template to rewrite the broken piece of chromosome.
WITH GENE DRIVE
1.0
Frequency
USING
GENE
DRIVE
TO CONTROL
MALARIA
Researchers can also use promoter sequences to ensure the endonuclease’s expression in the
germline, promoting its inheritance among offspring.
Germline promoter
0.5
0.0
0
10
20
30
Generations
With gene drive, the genetic modification
will quickly increase in frequency until it is
carried by all mosquitoes in the population.