Insights into Sex Chromosome Evolution and Aging from the Genome of a Short-Lived Fish

Abstract

The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in biomedical research. Here, we report a draft sequence of its genome that allowed us to uncover an intra-species Y chromosome polymorphism representing-in real time-different stages of sex chromosome formation that display features of early mammalian XY evolution "in action." Our data suggest that gdf6Y, encoding a TGF-β family growth factor, is the master sex-determining gene in N. furzeri. Moreover, we observed genomic clustering of aging-related genes, identified genes under positive selection, and revealed significant similarities of gene expression profiles between diapause and aging, particularly for genes controlling cell cycle and translation. The annotated genome sequence is provided as an online resource (http://www.nothobranchius.info/NFINgb).

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…To fill this gap, we and others have actively established the African turquoise killifish Nothobranchius furzeri as a research organism for vertebrate aging (Harel, Valenzano & Brunet, 2016; Polacik, Blazek & Reichard, 2016; Reichwald et al., 2015; Valdesalici & Cellerino, 2003; Valenzano, Sharp & Brunet, 2011; Valenzano et al., 2009, 2015). The turquoise killifish experiences a naturally fast‐aging process as part of its natural life history and is the shortest lived vertebrate that can be bred in captivity (Valdesalici & Cellerino, 2003).…”

“…Since then, the increased knowledge and improved husbandry have significantly lowered the early mortality rate in captivity. The median lifespan has been thus gradually extended and eventually stabilized at around 4–6 months (Figure 1), with similar numbers reported by multiple institutes across North America and Europe (Polacik et al., 2016; Reichwald et al., 2015; Valenzano et al., 2015). …”

“…The turquoise killifish strain that is most frequently used is the GRZ strain, an inbred line that originates from a sample collected in 1970 in the Gona‐Re‐Zhou National Park of Zimbabwe (Parle, 1970). Since then, several additional samples have been collected in Mozambique and Zimbabwe, and wild strains or strains derived from these samples (e.g., the MZM0403 and 0410 strains which were collected in 2004) have also been broadly used for a variety of studies (Bartakova et al., 2013; Baumgart et al., 2016; Blazek et al., 2017; Kirschner et al., 2012; Reichard, Polacik & Sedlacek, 2009; Reichwald et al., 2015; Terzibasi et al., 2008; Valenzano et al., 2009, 2015). In particular, these strains were used to identify the genetic architecture underlying phenotypic differences in these strains, such as color (Valenzano et al., 2009) and survival under specific laboratory environments (Baumgart et al., 2016; Blazek et al., 2017; Reichwald et al., 2015; Valenzano et al., 2015).…”

“…In 2015, two independent groups de novo assembled and annotated the turquoise killifish genome: Anne Brunet's laboratory at Stanford University (African Turquoise Killifish Genome Browser: http://africanturquoisekillifishbrowser.org/; Valenzano et al., 2015) and Matthias Platzer's laboratory in Jena, Germany ( Nothobranchius furzeri Genome Browser: http://nfingb.leibniz-fli.de/; Reichwald et al., 2015). Additionally, other genomic resources have also been established through the years, including genetic linkage maps, quantitative trait loci, over 150 microsatellite markers (Blazek et al., 2017; Kirschner et al., 2012; Valenzano et al., 2009), and numerous transcriptomic and epigenomic datasets of different tissues at different ages using various strains (Baumgart et al., 2012, 2014, 2016, 2017; D'Angelo et al., 2014; Ng'oma, Groth, Ripa, Platzer & Cellerino, 2014; Petzold et al., 2013).…”

“…Both commercially available systems and homemade racks for zebrafish can be converted for the turquoise killifish, without the need to add specific equipment and devices. The turquoise killifish has a XY sex‐determination system and shows sexual dimorphism after maturation (Reichwald et al., 2015; Valenzano et al., 2009). Males and females are roughly even‐numbered in offspring and are easily distinguished especially when they reach sexual maturity, as males are bigger in size and have colorful fins.…”