Unraveling the genotype by environment interaction in a thermosensitive fish with a polygenic sex determination system

Abstract

In most animals, sex determination occurs at conception, when sex chromosomes are segregated following Mendelian laws. However, in multiple reptiles and fishes, this genetic sex can be overridden by external factors after fertilization or birth. In some species, the genetic sex may also be governed by multiple genes, further limiting our understanding of sex determination in such species. We used the European sea bass (Dicentrarchus labrax) as a model and combined genomic (using a single nucleotide polymorphism chip) and transcriptomic (RNA-Sequencing) approaches to thoroughly depict this polygenic sex determination system and its interaction with temperature. We estimated genetic sex tendency (eGST), defined as the estimated genetic liability to become a given sex under a liability threshold model for sex determination, which accurately predicts the future phenotypic sex. We found evidence that energetic pathways, concerning the regulation of lipids and glucose, are involved in sex determination and could explain why females tend to exhibit higher energy levels and improved growth compared to males. Besides, early exposure to high-temperature up-regulated sox3, followed by sox9a in individuals with intermediate eGST, but not in individuals showing highly female-biased eGST, providing the most parsimonious explanation for temperature-induced masculinization. This gonadal state was maintained likely by DNA methylation and the up-regulation of several genes involved in histone modifications, including jmjd1c. Overall, we describe a sex determination system resulting from continuous genetic and environmental influences in an animal. Our results provide significant progress in our understanding of the mechanisms underlying temperature-induced masculinization in fish.

Effects of cortisol on female-to-male sex change in a wrasse

“…For example, while serum cortisol levels were observed to increase during sex change in the protandrous (male-to-female) cinnamon clownfish (Amphiprion melanopus), this rise took place in the late stages of the transformation [23], implying such variation may have been a consequence rather than a cause of sex change. This view is further supported by recent findings in the gonochoristic European sea bass (Dicentrarchus labrax), in which natural cortisol fluctuations were found to be independent from sex determination and differentiation mechanisms [24,25]. Such discoveries also agree with contrasting observations in reptilian systems, in which the effect of increased yolk corticosterone influenced sex ratios in some lizard species [26], but not others [27,28].…”

Epigenetic Regulation of Phenotypic Sexual Plasticity Inducing Skewed Sex Ratio in Zebrafish

“…However, the DNA methylation level of sox9a was increased only in the testes, but no significant difference was observed in the ovaries. Interestingly, the standard association between the hypermethylation and down-regulation of gene expression was not detected for sox9a in the testes at high temperature condition (Geffroy et al, 2021). Altogether, previous studies have verified the effect of DNA methylation changes on promoters of sex-biased genes in the regulation of two different sexes and in the generation of environmentally induced sex reversal mediated by temperature.…”

“…Global DNA methylation in Nile tilapia, Oreochromis niloticus, also represented an increase in the methylation levels of different chromosomes in both sexes in elevated temperature-exposed fish compared to the control group (Sun et al, 2016). A recent study on the genetic mechanisms underlying sex determination in European sea bass and its interaction with high ambient temperature revealed that temperature exposure leads to hypomethylation of sox3 gene, resulting in up-regulation of its expression in both testes and ovaries (Geffroy et al, 2021). However, the DNA methylation level of sox9a was increased only in the testes, but no significant difference was observed in the ovaries.…”

Deciphering sex-specific miRNAs as heat-recorders in zebrafish

“…Temperature increase influences sexual development by skewing sex ratios towards males in fish [5]. The study of the underlying epigenetic mechanisms of this masculinization have relied on DNA methylation analyses in the gonads of some fish species, like European sea bass [6,37], half-smooth tongue sole [8], tilapia [38], fugu [7] and zebrafish [9]. However, other epigenetic mechanisms, and specifically translation interference by miRNAs, have not yet been elucidated.…”