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Highly Efficient Generation of Germline Mutations Using CRISPR/Cas9 in the Speckled Wood Butterfly Pararge aegeria

Shoshan, Anna B. ; Tunström, Kalle LU ; Wheat, Christopher W. and Gotthard, Karl (2025) In Ecology and Evolution 15(7).
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, and thus, dedicated efforts to develop 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... (More)

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, and thus, dedicated efforts to develop 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 G0 and germline mutations. To explore what factors may affect the efficiency of transformation, we employed four alternative treatments, including variation in sgRNAs and their concentrations. Color changes in the head capsule of first larval instars, 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 G1 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 a 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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Ecology and Evolution
volume
15
issue
7
article number
e71624
publisher
Wiley-Blackwell
external identifiers
  • pmid:40589588
  • scopus:105009712652
ISSN
2045-7758
DOI
10.1002/ece3.71624
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Ecology and Evolution published by British Ecological Society and John Wiley & Sons Ltd.
id
b12963e4-5749-4d38-8b01-c8de7dc4bc96
date added to LUP
2025-12-11 14:25:09
date last changed
2026-01-08 17:29:36
@article{b12963e4-5749-4d38-8b01-c8de7dc4bc96,
  abstract     = {{<p>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 G<sub>0</sub> mutations, coupled with analyses of resulting mosaic phenotypes. However, studies of physiological phenotypes necessitate germline mutations in order to assess non-visible phenotypic effects, and thus, dedicated efforts to develop 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 G<sub>0</sub> and germline mutations. To explore what factors may affect the efficiency of transformation, we employed four alternative treatments, including variation in sgRNAs and their concentrations. Color changes in the head capsule of first larval instars, 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 G1 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 a 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.</p>}},
  author       = {{Shoshan, Anna B. and Tunström, Kalle and Wheat, Christopher W. and Gotthard, Karl}},
  issn         = {{2045-7758}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Ecology and Evolution}},
  title        = {{Highly Efficient Generation of Germline Mutations Using CRISPR/Cas9 in the Speckled Wood Butterfly Pararge aegeria}},
  url          = {{http://dx.doi.org/10.1002/ece3.71624}},
  doi          = {{10.1002/ece3.71624}},
  volume       = {{15}},
  year         = {{2025}},
}