Highly efficient generation of germline mutations using CRISPR/Cas9 in
the speckled wood butterfly Pararge aegeria
Abstract
To date, the use of CRISPR/Cas9 technology in ecological-model species
for validating genotype to phenotype connections has focused primarily
on visual phenotypes using G0 mutations coupled with analyses of
resulting mosaic phenotypes. However, studies of physiological
phenotypes necessitate germline mutations in order to assess non-visible
phenotypic effects, thus dedicated efforts to developing efficient
germline mutations in ecological model species are needed. Here we
applied the CRISPR/Cas9 technology to an ecological model species, the
speckled wood butterfly (Pararge aegeria). We targeted yellow-y, which
is required for the production of black melanin, as yellow-y loss of
function (LOF) mutations are not lethal and easy to phenotype, affording
efficient assessment of F0 and germline mutations. To explore what
factors may affect efficiency of transformation, we employed four
alternative treatments, including variation in sgRNAs and their
concentrations. Color changes in the head capsule of first larval instar
as well as adult wing color were used as indicators of successful
knockouts. Individuals with wings that were at least 50% transformed
were mated, with their F1 offspring assessed for the presence of
germline mutations. Our CRISPR/Cas9 technique was highly efficient at
generating LOF mutations in yellow-y. Across all treatments, nearly 80%
of adults exhibited mosaic LOF phenotypes, of which nearly 30% appeared
to have 100% LOF phenotypes. Crosses between adults exhibiting at least
50% LOF phenotypes resulted in fully transformed offspring, revealing
high incidence of germline LOF mutations in yellow-y. We provide a
detailed protocol on how to obtain high germline LOF mutation efficiency
in order to advance the study of genotype-phenotype connections for
non-visible physiological traits across natural populations of this and
other model ecological species.