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Miniscule differences between the sex chromosomes in the giant genome of a salamander, Ambystoma mexicanum

View ORCID ProfileMelissa C. Keinath, View ORCID ProfileNataliya Timoshevskaya, Vladimir A. Timoshevskiy, S. Randal Voss, View ORCID ProfileJeramiah J. Smith
doi: https://doi.org/10.1101/354092
Melissa C. Keinath
1Department of Biology, University of Kentucky, Lexington, KY, USA
2Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA
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  • For correspondence: keinath@carnegiescience.edu Jjsmit3@uky.edu
Nataliya Timoshevskaya
1Department of Biology, University of Kentucky, Lexington, KY, USA
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Vladimir A. Timoshevskiy
1Department of Biology, University of Kentucky, Lexington, KY, USA
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S. Randal Voss
3Department of Neuroscience, Spinal Cord & Brain Injury Research Center (SCoBIRC), & Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY, USA
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Jeramiah J. Smith
1Department of Biology, University of Kentucky, Lexington, KY, USA
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  • For correspondence: keinath@carnegiescience.edu Jjsmit3@uky.edu
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ABSTRACT

In the Mexican axolotl (Ambystoma mexicanum) sex is known to be determined by a single Mendelian factor, yet the sex chromosomes of this model salamander do not exhibit morphological differentiation that is typical of many vertebrate taxa that possess a single sex-determining locus. Differentiated sex chromosomes are thought to evolve rapidly in the context of a Mendelian sex-determining gene and, therefore, undifferentiated chromosomes provide an exceptional opportunity to reconstruct early events in sex chromosome evolution. Whole chromosome sequencing, whole genome resequencing (48 individuals from a backcross of axolotl and tiger salamander) and in situ hybridization were used to identify a homomorphic chromosome that carries an A. mexicanum sex determining factor and identify sequences that are present only on the W chromosome. Altogether, these sequences cover ~300 kb, or roughly 1/100,000th of the ~32 Gb genome. Notably, these W-specific sequences also contain a recently duplicated copy of the ATRX gene: a known component of mammalian sex-determining pathways. This gene (designated ATRW) is one of the few functional (non-repetitive) genes in the chromosomal segment and maps to the tip of chromosome 9 near the marker E24C3, which was previously found to be linked to the sex-determining locus. These analyses provide highly predictive markers for diagnosing sex in A. mexicanum and identify ATRW as a strong candidate for the primary sex determining locus or alternately a strong candidate for a recently acquired, sexually antagonistic gene.

AUTHOR SUMMARY Sex chromosomes are thought to follow fairly stereotypical evolutionary trajectories that result in differentiation of sex-specific chromosomes. In the salamander A. mexicanum (the axolotl), sex is determined by a single Mendelian locus, yet the sex chromosomes are essentially undifferentiated, suggesting that these sex chromosomes have recently acquired a sex locus and are in the early stages of differentiating. Although Mendelian sex determination was first reported for the axolotl more than 70 years ago, no sex-specific sequences have been identified for this important model species. Here, we apply new technologies and approaches to identify and validate a tiny region of female-specific DNA within the gigantic genome of the axolotl (1/100,000th of the genome). This region contains a limited number of genes, including a duplicate copy of the ATRX gene which, has been previously shown to contribute to mammalian sex determination. Our analyses suggest that this gene, which we refer to as ATRW, evolved from a recent duplication and presents a strong candidate for the primary sex determining factor of the axolotl, or alternately a recently evolved sexually antagonistic gene.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 22, 2018.
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Miniscule differences between the sex chromosomes in the giant genome of a salamander, Ambystoma mexicanum
Melissa C. Keinath, Nataliya Timoshevskaya, Vladimir A. Timoshevskiy, S. Randal Voss, Jeramiah J. Smith
bioRxiv 354092; doi: https://doi.org/10.1101/354092
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Miniscule differences between the sex chromosomes in the giant genome of a salamander, Ambystoma mexicanum
Melissa C. Keinath, Nataliya Timoshevskaya, Vladimir A. Timoshevskiy, S. Randal Voss, Jeramiah J. Smith
bioRxiv 354092; doi: https://doi.org/10.1101/354092

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