Sox5 is Involved in Germ-cell Regulation and Sex Determination in Medaka Following Co-option of Nested Transposable Elements

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2018 Jan 31

PMID 29378592

Citations 26

Authors

Manfred Schartl

Susanne Schories

Yuko Wakamatsu

Yusuke Nagao

Hisashi Hashimoto

Chloe Bertin

Brigitte Mourot

Cornelia Schmidt

Dagmar Wilhelm

Lazaro Centanin

Yann Guiguen

Amaury Herpin

Affiliations

Soon will be listed here.

Abstract

Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination.

Results: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal.

Conclusions: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.

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