Reduced Activity of SRY and its Target Enhancer Sox9-TESCO in a Mouse Species with X*Y Sex Reversal.
In most eutherian mammals, sex determination is governed by the Y-linked gene Sry, but in African pygmy mice Mus minutoides, Sry action is overridden by a variant X chromosome (X*), yielding X*Y females. We hypothesized that X*Y sex reversal may be underpinned not only by neomorphic X chromosome functionality, but also by a compromised Sry pathway. Here, we show that neither M. minutoides SRY nor its target, the Sox9-TESCO enhancer, had appreciable transcriptional activity in in vitro assays, correlating with sequence degradation compared to Mus musculus counterparts. However, M. minutoides SRY activated its cognate TESCO to a moderate degree, and can clearly engage the male pathway in M. minutoides in the wild, indicating that SRY and TESCO may have co-evolved in M. minutoides to retain function above a threshold level. We suggest that weakening of the SRY/TESCO nexus may have facilitated the rise and spread of a variant X* chromosome carrying female-inducing modifier gene(s).
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Liang
L
Zhao
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Alexander
A
Quinn
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Ee Ting
ET
Ng
Institut des Sciences de l'Evolution de Montpellier, Université Montpellier II, CNRS, Montpellier, France.
Frederic
F
Veyrunes
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Peter
P
Koopman
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D017930:Genes, Reporter; D057809:HEK293 Cells; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008957:Models, Genetic; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D055550:Protein Stability; D055758:SOX9 Transcription Factor / Q000235:genetics*; D019849:Sex Determination Processes / Q000235:genetics*; D051876:Sex-Determining Region Y Protein / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
D010455:Peptides; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C097188:polyglutamine