Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology.

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Main Authors: Kukoly, Lindsey M, Porter, Sarah R, Jordan, Danielle C, Murphy, Heather A, Knytl, Martin, Shaidani, Nikko, Thomas, William R, Anderson, Carl, Dworkin, Ian, Horb, Marko E, Evans, Ben J
Format: Artículo científico
Language:en
Published: PLoS genetics 2026
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author Kukoly, Lindsey M
Porter, Sarah R
Jordan, Danielle C
Murphy, Heather A
Knytl, Martin
Shaidani, Nikko
Thomas, William R
Anderson, Carl
Dworkin, Ian
Horb, Marko E
Evans, Ben J
author_facet Kukoly, Lindsey M
Porter, Sarah R
Jordan, Danielle C
Murphy, Heather A
Knytl, Martin
Shaidani, Nikko
Thomas, William R
Anderson, Carl
Dworkin, Ian
Horb, Marko E
Evans, Ben J
Kukoly, Lindsey M
Porter, Sarah R
Jordan, Danielle C
Murphy, Heather A
Knytl, Martin
Shaidani, Nikko
Thomas, William R
Anderson, Carl
Dworkin, Ian
Horb, Marko E
Evans, Ben J
collection PubMed - marine biology
contents Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology. Kukoly, Lindsey M Porter, Sarah R Jordan, Danielle C Murphy, Heather A Knytl, Martin Shaidani, Nikko Thomas, William R Anderson, Carl Dworkin, Ian Horb, Marko E Evans, Ben J Animals Female Transcription Factors Male Xenopus Proteins Xenopus laevis Evolution, Molecular Gene Expression Regulation, Developmental Xenopus Sex Differentiation Sex Determination Processes Fertility Spermatogenesis Oogenesis The doublesex and mab-3 related transcription factor 1 (dmrt1) plays a crucial role in metazoan sexual differentiation. This gene, or its paralogs, independently became triggers for sex determination several times, including in the tetraploid African clawed frog Xenopus laevis. To explore functional evolution of this gene, we generated knockout lines of each of two dmrt1 homeologs in X. laevis and an ortholog in the closely related diploid Western clawed frog X. tropicalis. Our findings evidence sex-specific functional evolution following duplication by allotetraploidization in an ancestor of X. laevis. In females, dmrt1 was essential for fertility and oogenesis in the Xenopus ancestor, but this important function was lost (subfunctionalized) in one X. laevis homeolog (dmrt1.S) after allotetraploidization. In males - in sharp contrast - dmrt1 was not essential for fertility and spermatogenesis in the Xenopus ancestor, but this essentiality was acquired (neofunctionalized) in the other X. laevis homeolog (dmrt1.L) after allotetraploidization. Transcriptomic analysis of the mesonephros/gonad complex during sexual differentiation identifies distinctive patterns of dysregulation in male and female knockouts of dmrt1.L and dmrt1.S relative to same-sex wildtype siblings, including possible autocatalysis of dmrt1.L and activation of the female-determining gene dm-w. Previous work demonstrates that dm-w was recently derived from partial gene duplication of dmrt1.S - a gene that our analysis demonstrates is non-essential in both sexes. Thus, in X. laevis, a developmental system was pushed past a "tipping point" to a novel state where sexual differentiation is now orchestrated by a sex-specific duplicate of a dispensable gene.
format Artículo científico
id pubmed_41481615
institution PubMed
language en
publishDate 2026
publisher PLoS genetics
record_format pubmed
spellingShingle Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology.
Kukoly, Lindsey M
Porter, Sarah R
Jordan, Danielle C
Murphy, Heather A
Knytl, Martin
Shaidani, Nikko
Thomas, William R
Anderson, Carl
Dworkin, Ian
Horb, Marko E
Evans, Ben J
Animals
Female
Transcription Factors
Male
Xenopus Proteins
Xenopus laevis
Evolution, Molecular
Gene Expression Regulation, Developmental
Xenopus
Sex Differentiation
Sex Determination Processes
Fertility
Spermatogenesis
Oogenesis
Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology. Kukoly, Lindsey M Porter, Sarah R Jordan, Danielle C Murphy, Heather A Knytl, Martin Shaidani, Nikko Thomas, William R Anderson, Carl Dworkin, Ian Horb, Marko E Evans, Ben J Animals Female Transcription Factors Male Xenopus Proteins Xenopus laevis Evolution, Molecular Gene Expression Regulation, Developmental Xenopus Sex Differentiation Sex Determination Processes Fertility Spermatogenesis Oogenesis The doublesex and mab-3 related transcription factor 1 (dmrt1) plays a crucial role in metazoan sexual differentiation. This gene, or its paralogs, independently became triggers for sex determination several times, including in the tetraploid African clawed frog Xenopus laevis. To explore functional evolution of this gene, we generated knockout lines of each of two dmrt1 homeologs in X. laevis and an ortholog in the closely related diploid Western clawed frog X. tropicalis. Our findings evidence sex-specific functional evolution following duplication by allotetraploidization in an ancestor of X. laevis. In females, dmrt1 was essential for fertility and oogenesis in the Xenopus ancestor, but this important function was lost (subfunctionalized) in one X. laevis homeolog (dmrt1.S) after allotetraploidization. In males - in sharp contrast - dmrt1 was not essential for fertility and spermatogenesis in the Xenopus ancestor, but this essentiality was acquired (neofunctionalized) in the other X. laevis homeolog (dmrt1.L) after allotetraploidization. Transcriptomic analysis of the mesonephros/gonad complex during sexual differentiation identifies distinctive patterns of dysregulation in male and female knockouts of dmrt1.L and dmrt1.S relative to same-sex wildtype siblings, including possible autocatalysis of dmrt1.L and activation of the female-determining gene dm-w. Previous work demonstrates that dm-w was recently derived from partial gene duplication of dmrt1.S - a gene that our analysis demonstrates is non-essential in both sexes. Thus, in X. laevis, a developmental system was pushed past a "tipping point" to a novel state where sexual differentiation is now orchestrated by a sex-specific duplicate of a dispensable gene.
title Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology.
topic Animals
Female
Transcription Factors
Male
Xenopus Proteins
Xenopus laevis
Evolution, Molecular
Gene Expression Regulation, Developmental
Xenopus
Sex Differentiation
Sex Determination Processes
Fertility
Spermatogenesis
Oogenesis
url https://pubmed.ncbi.nlm.nih.gov/41481615/