An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

Bradley, Kevin M.; Breyer, Joan P.; Melville, D.; Broman, Karl W.; Knapik, Ela W.; Smith, Jeffrey R.

doi:10.1534/g3.111.000190

Cited by 153 publications

(154 citation statements)

References 38 publications

(43 reference statements)

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…These data support the earlier claims that sex determination in domesticated zebrafish is polygenic (30,31,33,51). Then, with the temperature experiments performed in this study, we added an additional level of complexity to this polygenic system by showing different family-by-temperature crossing reaction norms, hence demonstrating the existence of GxE interactions.…”

Section: Discussionsupporting

confidence: 89%

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

Ribas

Liew

Díaz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

110

136

View full text Add to dashboard Cite

Understanding environmental influences on sex ratios is important for the study of the evolution of sex-determining mechanisms and for evaluating the effects of global warming and chemical pollution. Fishes exhibit sexual plasticity, but the underlying mechanisms of environmental effects on their reproduction are unclear even in the well-established teleost research model, the zebrafish. Here we established the conditions to study the effects of elevated temperature on zebrafish sex. We showed that sex ratio response to elevated temperature is family-specific and typically leads to masculinization (female-to-male sex reversal), resulting in neomales. These results uncovered genotype-by-environment interactions that support a polygenic sex determination system in domesticated (laboratory) zebrafish. We found that some heat-treated fish had gene expression profiles similar to untreated controls of the same sex, indicating that they were resistant to thermal effects. Further, most neomales had gonadal transcriptomes similar to that of regular males. Strikingly, we discovered heat-treated females that displayed a normal ovarian phenotype but with a "male-like" gonadal transcriptome. Such major transcriptomic reprogramming with preserved organ structure has never been reported. Juveniles were also found to have a male-like transcriptome shortly after exposure to heat. These findings were validated by analyzing the expression of genes and signaling pathways associated with sex differentiation. Our results revealed a lasting thermal effect on zebrafish gonads, suggesting new avenues for detection of functional consequences of elevated temperature in natural fish populations in a global warming scenario.A major paradox in developmental biology is the lack of conservation of sex-determining mechanisms even in closely related taxa (1). Thus, in mammals and birds, sex is genetically canalized by a chromosomal sex determination (CSD) system of male (XX/XY in mammals) or female (ZW/ZZ in birds) heterogamety, driven by the action of a master sex-determining gene: sry in mammals and dmrt1 in birds (1). In contrast, fish sex can be very plastic, with the combination of genetic and environmental influences (2). In addition to fish species with CSD, there are species with polygenic sex determination (PSD), in which sex depends on the combined action of several promale and profemale genetic factors, and species with temperature-dependent sex determination (TSD) (3). Understanding how the environment influences sex ratios in vertebrates is of fundamental importance in the study of the evolution of sex-determining mechanisms (4, 5). It is also of practical relevance in evaluating the effects of climate change and chemical pollution (6, 7).The effects of temperature on gene expression during sex differentiation have been investigated in different teleost species, including the African catfish, Clarias gariepinus (8), European sea bass, Dicentrarchus labrax (9, 10), Japanese flounder, Paralichthys olivaceus (11), pejerrey, Odontesthes...

show abstract

Section: Discussionsupporting

confidence: 89%

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

Ribas

Liew

Díaz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

110

136

View full text Add to dashboard Cite

show abstract

“…Gene expression of cyp19a1a encoding aromatase was up-regulated in the few females remaining in the inbred, elevated temperature, and/or high-level clotrimazole exposure treatments, and we hypothesize that this up-regulation was the result of a compensatory response to P450(CYP)19 aromatase inhibition in these individuals. Although many other genes have been implicated in sex determination and differentiation in zebrafish (66,67), these genes appear to vary in importance between different strains (68) % 66 80 68 79 70 77 71 80 69 78 Total number of fish per treatment combination Table S1.2).…”

Section: Discussionmentioning

confidence: 99%

Climate change and pollution speed declines in zebrafish populations

Brown

Owen

Peters

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Endocrine disrupting chemicals (EDCs) are potent environmental contaminants, and their effects on wildlife populations could be exacerbated by climate change, especially in species with environmental sex determination. Endangered species may be particularly at risk because inbreeding depression and stochastic fluctuations in male and female numbers are often observed in the small populations that typify these taxa. Here, we assessed the interactive effects of water temperature and EDC exposure on sexual development and population viability of inbred and outbred zebrafish (Danio rerio). Water temperatures adopted were 28°C (current ambient mean spawning temperature) and 33°C (projected for the year 2100). The EDC selected was clotrimazole (at 2 μg/L and 10 μg/L), a widely used antifungal chemical that inhibits a key steroidogenic enzyme [cytochrome P450(CYP19) aromatase] required for estrogen synthesis in vertebrates. Elevated water temperature and clotrimazole exposure independently induced maleskewed sex ratios, and the effects of clotrimazole were greater at the higher temperature. Male sex ratio skews also occurred for the lower clotrimazole exposure concentration at the higher water temperature in inbred fish but not in outbred fish. Population viability analysis showed that population growth rates declined sharply in response to male skews and declines for inbred populations occurred at lower male skews than for outbred populations. These results indicate that elevated temperature associated with climate change can amplify the effects of EDCs and these effects are likely to be most acute in small, inbred populations exhibiting environmental sex determination and/or differentiation.

show abstract

“…This result is expected if zebrafish has a genetic basis for sex determination with polygenic control that differs among strains (Liew et al 2012). Furthermore, recent studies of sex genetics in different zebrafish strains identified sex-associated loci, confirming a genetic component to sex determination, but different studies identified different sex-associated loci (Orban et al 2009;Siegfried 2010;Tong et al 2010;Bradley et al 2011;Anderson et al 2012;Liew et al 2012;Howe et al 2013;Liew and Orban 2014). A cross between a female of the NA (Nadia) natural strain by a male of the AB laboratory strain identified a single sex-linked locus on zebrafish chromosome 4 (Chr4) while the reciprocal mating (female-AB-by-male-NA) showed sexassociated loci on both Chr4 and Chr3 (Anderson et al 2012).…”

mentioning

confidence: 86%

“…A cross between a female of the NA (Nadia) natural strain by a male of the AB laboratory strain identified a single sex-linked locus on zebrafish chromosome 4 (Chr4) while the reciprocal mating (female-AB-by-male-NA) showed sexassociated loci on both Chr4 and Chr3 (Anderson et al 2012). In contrast, analysis of a female-AB-by-male-IN (India) cross identified sex-linked loci on Chr5 and Chr16 but none on Chr3 or Chr4 (Bradley et al 2011). An F 2 map constructed from a gynogenetic doubled-haploid TU female and a gynogenetic doubled-haploid AB male (i.e., both parents had only female-derived chromosomes) identified a sex-linked region on Chr16 that does not overlap with the one observed in the AB-by-IN mating (Bradley et al 2011;Howe et al 2013).…”

mentioning

confidence: 99%

Wild Sex in Zebrafish: Loss of the Natural Sex Determinant in Domesticated Strains

et al. 2014

View full text Add to dashboard Cite

Sex determination can be robustly genetic, strongly environmental, or genetic subject to environmental perturbation. The genetic basis of sex determination is unknown for zebrafish (Danio rerio), a model for development and human health. We used RADtag population genomics to identify sex-linked polymorphisms. After verifying this "RAD-sex" method on medaka (Oryzias latipes), we studied two domesticated zebrafish strains (AB and TU), two natural laboratory strains (WIK and EKW), and two recent isolates from nature (NA and CB). All four natural strains had a single sex-linked region at the right tip of chromosome 4, enabling sex genotyping by PCR. Genotypes for the single nucleotide polymorphism (SNP) with the strongest statistical association to sex suggested that wild zebrafish have WZ/ZZ sex chromosomes. In natural strains, "male genotypes" became males and some "female genotypes" also became males, suggesting that the environment or genetic background can cause female-to-male sex reversal. Surprisingly, TU and AB lacked detectable sex-linked loci. Phylogenomics rooted on D. nigrofasciatus verified that all strains are monophyletic. Because AB and TU branched as a monophyletic clade, we could not rule out shared loss of the wild sex locus in a common ancestor despite their independent domestication. Mitochondrial DNA sequences showed that investigated strains represent only one of the three identified zebrafish haplogroups. Results suggest that zebrafish in nature possess a WZ/ZZ sex-determination mechanism with a major determinant lying near the right telomere of chromosome 4 that was modified during domestication. Strains providing the zebrafish reference genome lack key components of the natural sex-determination system but may have evolved variant sex-determining mechanisms during two decades in laboratory culture.. . .researchers using standard lines of zebrafish that have long been maintained in laboratories are often plagued by severe sex ratio distortions. . .. C. Lawrence, J. P. Ebersole, and R. V. Kesseli (2008) C ONSIDERING the fundamental importance of sex for species propagation, it is surprising that primary sexdetermining mechanisms are not strongly conserved among animal taxa (Bull 1983;Charlesworth 1996;Ming et al. 2011;Bachtrog et al. 2014). Closely related species or even populations of the same species can have different sexdetermining mechanisms (Takehana et al. 2007;Ross et al. 2009;Kobayashi et al. 2013;Heule et al. 2014;Larney et al. 2014). Zebrafish (Danio rerio) is a popular model for studies of vertebrate development, behavior, physiology, evolution, disease, and human health (Mills et al. 2007;Seth et al. 2013;Braasch et al. 2014;Ota and Kawahara 2014;Wilkinson et al. 2014), but researchers struggle with highly variable and distorted sex ratios, and investigations into the genetic nature of zebrafish sex determination are conflicting. To help understand these issues, we conducted a population genomic study of sex determination in multiple zebrafish strains. Zebrafish exhibit...

show abstract

An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

Cited by 153 publications

References 38 publications

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

Climate change and pollution speed declines in zebrafish populations

Wild Sex in Zebrafish: Loss of the Natural Sex Determinant in Domesticated Strains

Contact Info

Product

Resources

About