pests [11] and will probably be useful
also to control human disease vectors,
the insect in the transmission of
vector-borne diseases is only annoying
but not the cause of the illness itself.
Therefore, replacement strategies have
been considered that would not
suppress or eradicate the insect
vector but instead make it refractory
to the transmission of the disease —
causing pathogens [3]. To locally
restrict the spread of or actually
recall the refractoriness providing
transgenes, the group of Bruce Hay
has successfully tested a controllable
synthetic gene drive mechanism based
on the principle of underdominance
using an artificial MEDEA (maternal
effect dominant embryonic arrest)
system in the insect model Drosophila
melanogaster [8].
Maternal-effect selfish genes were
first described in the red flour beetle
Tribolium castaneum and called
MEDEA [17] — a fitting acronym as in
Greek mythology Medea killed her
kids sired by the ‘wrong’ man, Jason,
after he rejected her. Tribolium
Medea elements are based on a still
hypothetical maternal lethal activity
that kills all progeny not bearing the
correct Medea allele [18]. As this
‘selfish’ mechanism ensures that
progeny of carrier mothers only survive
when they inherit from either parent a
copy of this genetic element, the
inheritance is non-Mendelian
(Figure 1A) and leads to a population
spread of the genetic element. Based
on this concept, a synthetic MEDEA
system was designed in Drosophila
[19] using maternally expressed
microRNAs against a maternally
provided mRNA that is necessary for
embryo survival. The zygotic rescue
activity in this synthetic system is
due to a transgene from which the
respective mRNA is transcribed
and which is insensitive to the
microRNAs (Figure 1B). This system
drives population replacement by
spreading itself in a non-Mendelian
but uncontrollable manner [19]. Hay
and colleagues [8] have further
developed this synthetic system into
double-MEDEA (Figure 2A) to get
control over the transgene spread by
under- or overdominance.
Underdominance (heterozygote
inferiority) means that the fitness of
both homozygous genotypes is higher
than of the heterozygous genotype
[20]. Over time, this leads to disruptive
selection towards either of the two