The African Turquoise Killifish Genome Provides Insights into Evolution and Genetic Architecture of Lifespan

Abstract

Summary Lifespan is a remarkably diverse trait ranging from a few days to several hundred years in nature, but the mechanisms underlying the evolution of lifespan differences remain elusive. Here we de novo assemble a reference genome for the naturally short-lived African turquoise killifish, providing a unique resource for comparative and experimental genomics. The identification of genes under positive selection in this fish reveals potential candidates to explain its compressed lifespan. Several aging genes are under positive selection in this short-lived fish and long-lived species, raising the intriguing possibility that the same gene could underlie evolution of both compressed and extended lifespans. Comparative genomics and linkage analysis identify candidate genes associated with lifespan differences between various turquoise killifish strains. Remarkably, these genes are clustered on the sex chromosome, suggesting that short lifespan might have co-evolved with sex determination. Our study provides insights into the evolutionary forces that shape lifespan in nature.

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).…”

Evolutionary toxicology in an omics world

“…Such projects are currently underway in both Fundulus heteroclitus (Reid et al., 2016) and F. grandis , and represent one of the most in‐depth approaches in evolutionary toxicology. The power of this approach is exemplified in a recent study of aging in turquoise killifish, Nothobranchius furzeri , which identified the specific genes responsible for an incredibly rapid generation turnover in this fish (Valenzano et al., 2015). Studies suggest that in order to be able to predict many population‐wide statistics with power, at least 20–30 individuals per population need to be sequenced in order to reliably measure heterozygosity and to test for Hardy–Weinberg equilibrium at all loci (Luikart et al., 2003).…”