Repeated co-option of HMG-box genes for sex determination in brown algae and animals

Abstract

In many eukaryotes, genetic sex determination is not governed by XX/XY or ZW/ZZ systems but by a specialized region on the poorly studied U (female) or V (male) sex chromosomes. Previous studies have hinted at the existence of a dominant male-sex factor on the V chromosome in brown algae, a group of multicellular eukaryotes distantly related to animals and plants. The nature of this factor has remained elusive. Here, we demonstrate that an HMG-box gene acts as the male-determining factor in brown algae, mirroring the role HMG-box genes play in sex determination in animals. Over a billion-year evolutionary timeline, these lineages have independently co-opted the HMG box for male determination, representing a paradigm for evolution’s ability to recurrently use the same genetic “toolkit” to accomplish similar tasks.

Interactions between U and V sex chromosomes during the life cycle of Ectocarpus

“…The diploid homozygous loss of the TALE-HD transcription factor ORO results in a male gametophyte-like phenotype that produces functional male gametes capable of undergoing fertilization, despite the presence of both the U and V sex chromosome ( Ahmed et al, 2014 ). This is consistent with the presence of the male sex-determining gene HMG-sex on the SDR of the V chromosome ( Luthringer et al, 2024 ). Interestingly, we observed that HMG-sex expression is de-repressed in oro;oro mutants, suggesting that the regulatory activity of ORO is required to repress HMG-sex expression, be this directly or indirectly.…”

“…This suggests that ORO activity may be required to suppress HMG-sex expression in the WT sporophyte in a manner similar to other V-linked genes ( Fig. 2B,C ) ( Luthringer et al, 2024 ). Given the role HMG-sex plays in male sex determination ( Luthringer et al, 2024 ), its increased expression in diploid oro;oro mutants likely explains the male sex phenotype observed in these lines.…”

“…This suggests that the V chromosome harbours a dominant genetic factor that is responsible for specification of male gametophytic fate. Consistent with this idea, a gene present on the V chromosome encodes an HMG transcription factor called HMG-sex that acts a master regulator of male sex determination in Ectocarpus and kelps ( Luthringer et al, 2024 ). Consistent with this, HMG-sex transcripts were barely detectable in WT sporophytes compared with male gametophytes ( Fig.…”

“…2B,C ) ( Luthringer et al, 2024 ). Given the role HMG-sex plays in male sex determination ( Luthringer et al, 2024 ), its increased expression in diploid oro;oro mutants likely explains the male sex phenotype observed in these lines. Indeed, an hmg-sex knockout in diploid oro;oro mutants converts male sex to a female phenotype ( Luthringer et al, 2024 ), providing further indication for a link between ORO activity and the repression of HMG-sex in the diploid sporophyte.…”

“…Strikingly, diploid oro;oro mutants bear both a U and V sex chromosome, yet phenotypically behave like a male gametophyte, suggesting that the SDR of the male V chromosome is genetically dominant over that of the female U ( Ahmed et al, 2014 ). This is suggestive of a master regulatory gene on the male SDR that triggers male development and/or suppresses female development, which has recently been shown to be a male SDR-specific gene encoding a high-mobility group (HMG) transcription factor ( Lipinska et al, 2017 ; Luthringer et al, 2024 ; Müller et al, 2021 ). The observation that the V acts dominantly over the U in a gametophyte context thus provides a key opportunity to gain further insight into the genetic and molecular mechanisms underlying UV sex determination.…”