Laboratory zebrafish hide a dirty little secret. Although the tiny fish have proven to be a vital model of vertebrate development and disease genetics, zebrafish reproduction—at least in the lab—has wildly variable outcomes. Offspring sex ratios can vary from extremely male-biased to extremely female-biased, depending on which breeding pairs serve as parents.

The reason for this variability, and the basics of how zebrafish determine their sex, have remained a mystery for decades. The major factors affecting sex ratios in this species are genetic, but zebrafish lack obvious sex chromosomes, which in other species are often mismatched sizes. Several sex-linked loci have been located in zebrafish, but studies that used different strains identified different loci. One explanation is that zebrafish sex determination may be a complex, polygenic trait. The title of a recent review probably summarizes the situation best: “Zebrafish sex: a complicated affair.”

Now, a paper by Wilson et al. in the November issue of GENETICS has resolved a major source of the confusion by concluding that laboratory zebrafish strains lack the natural sex determination system of their wild counterparts.

The study, led by John Postlethwait of the University of Oregon, used the “RAD-sex” method to identify SNPs found more frequently in one sex than the other. In this approach, a genome-wide association study is used to compare genotype data from males and females derived from RAD-tags (restriction site-associated DNA tags).

The team verified that RAD-sex works by analyzing a fish species in which the sex determination locus is already known. But to their surprise, trying the same approach with the two most commonly-used zebrafish strains yielded no associations. None of the more than 30,000 tested SNPs were significantly associated with sex. In contrast, tests of the “natural” zebrafish strain included as a control revealed several strong associations, all mapping to the same 1.5 Mb region of the genome. These fish had spent only eight generations in the lab and had not been subjected to the intense selective breeding procedures used to establish true laboratory strains.

Suspecting that the discrepancy between the RAD-sex results was due to the difference between “wild” and “lab” breeding histories, the authors repeated the procedure with three more unselected strains derived from wild stocks. The results confirmed the location of the natural sex determination locus, and suggested that zebrafish use a sex determination system similar to that found in birds, in which females are heterogametic (heterozygous at the sex locus) and males homogametic.

So what happened to the lab strains? There’s not enough data to say for sure, but it seems likely that —independently in the two strains—domestication has disrupted the function of the natural sex determination system. After decades in culture, these fish seem to have developed or strengthened alternative methods for sex determination, relying more heavily on environmental and multiple weak genetic factors than their free-range cousins. With further study, lab zebrafish might even become a powerful model for the rapid evolution of new sex determination systems.

The results also remind us that evolution rarely stops, even in the lab.

 

 

CITATION: Wilson C.A., B. M. McCluskey, A. Amores, Y.-l. Yan, T. A. Titus, J. L. Anderson, P. Batzel, M. J. Carvan, M. Schartl & J. H. Postlethwait & (2014). Wild Sex in Zebrafish: Loss of the Natural Sex Determinant in Domesticated Strains, Genetics, 198 (3) 1291-1308. http://www.genetics.org/content/198/3/1291
DOI: http://dx.doi.org/10.1534/genetics.114.169284

, , , ,

Cristy Gelling is a science writer, lapsed yeast geneticist, and former Communications Director at the GSA.

View all posts by Cristy Gelling »

Read more in

  • Early Career Leadership Spotlight: Julio Molina Pineda 

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Julio Molina Pineda  Policy and Advocacy University of Arkansas Research Interest  My research interests focus on using model organisms to genetically dissect complex traits related to human disease. My…

  • Peiwei Chen

    Early Career Leadership Spotlight: Peiwei Chen

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Peiwei Chen Accessibility Subcommittee California Institute of Technology Research Interest Far from a harmonious place, the genome is a battleground, where every bit of DNA fights for inheritance and…

  • #Dros23 GSA Poster Award winners

    We are pleased to announce the GSA Poster Award winners from the 64th Annual Drosophila Research Conference! Undergraduate and graduate student members of the GSA were eligible for the awards, and a hard-working team of postdocs volunteered their time as judges. Congratulations to all! Undergraduate Students 1st Place: Sofia Karter Lopez, University of Toronto “Rab11 mediates E-cadherin recycling during…

  • Congratulations to the Fall 2022 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Fall 2022! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • GENETICS & G3 editors

    New editors join GENETICS, G3 editorial boards

    Several new editors are joining the GSA Journals. We’re excited to welcome Ricardo Zayas to the GENETICS editorial board under the Molecular Genetics of Development section, and on the G3: Genes|Genomes|Genetics board, we welcome Polly Campbell, Kevin Vogel, Joe Parker, and Ricardo Mallarino. Ricardo Zayas Associate Editor Ricardo Zayas is a Professor of Biology at…

  • Worms and Flies Provide Key Clues to Medical Mystery

    This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee. By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was…

  • Congratulations to the 2023 Early Career Leadership Program Cohort!

    The Genetics Society of America (GSA) is excited to announce the latest cohort of student, postdoc, and early-career research leaders joining the Early Career Leadership Program.  Participants receive training and mentoring while serving on committees charged with understanding the needs, interests, concerns, and challenges of early career scientist members of the GSA. As part of…

  • 64th Annual Drosophila Research Conference March 1–5, 2023 Chicago, IL and online

    GSA LOCI: Local Outreach Community Initiatives @ GSA Conferences

    Highlights: Local Outreach Community Initiatives (LOCI): The Genetics Society of America is committed to supporting the communities of the host cities of our conferences. This new year, we are excited to reconnect with our GSA community in meaningful ways within and beyond our existing programming. The GSA membership has created a caring and supportive environment…

  • Headshots of the 5 elected members of the GSA Board of Directors on a black background.

    New members of the GSA Board of Directors: 2023–2025

    We are pleased to announce the election of five new leaders to the GSA Board of Directors: 2023 Vice President/2024 President Mariana Wolfner Distinguished Professor of Molecular Biology and Genetics and Stephen H. Weiss Presidential Fellow My research has focused on the genes and pathways that mediate sexual development and reproduction, primarily in Drosophila. From…

  • Lance David Miller

    Lance David Miller: Lighting Your Own Fire by Finding the Right Resources

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…

  • Graça Almeida-Porada: The Importance of Communication in a Technologically Advancing World

    By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…