Sexual maturation in salmon - Causal genetic variants and the link between epigenetic and genetic contribution to the trait (MATGEN)

In the MATGEN project, we have studied the relationship between genetic predisposition for age at sexual maturation and how environmental signals can modulate this trait. The background for the project was that we had in an earlier project (SALMAT), shown that a single locus in the salmon genome greatly contributed to determining the sea age at sexual maturation in salmon. This has opened up an opportunity to directly investigate the connection between genetic and environmentally controlled regulation of age at sexual maturation in salmon and its application in aquaculture practices. The identified genetic region that strongly influences age at sexual maturation in salmon contains three genes, where vestigial-like gene 3 (vgll3) is the gene located in the part of the region that shows the strongest significance for the trait. Through studies of the testis, we have seen that vgll3 is expressed in Sertoli (males) and granulosa (females) in salmon gonads, cells essential for growth and development gametes in animals. We have also shown that the vgll3 gene is downregulated in the testis when males enter sexual maturity. We also have results that indicate that the vgll3 gene controls the time for sexual maturation in salmon via an unknown endocrine signal chain that results in less expression of the maturation inducing gene fsh, in fish that are genetically predisposed to mature late. In addition, we have observed that the genotype that controls early sexual maturation does not control time for sexual maturation in females and in breeding males, the effect of the sexual maturation locus is weaker than in wild males. Furthermore, we have results in the project that show that feeding level affects the time of maturation locus and in fish with reduced feeding, the locus effect is stronger compared with fish fed under a normal feeding regime.

Våre studier har vist at bruk av det seint modnende vgll3a allelen kan minke hyppighet av før tidlig kjønnsmodning i hanner, men effekten av lokuset er mindre i oppdrettsfisk sammenlignet med villfisk og det ser ut som fôring, bruk av høyere temperaturer og kontinuerlig lys kan svekke effekten av vgll3a allelavhengig pubertetshemming. Siden vi har oppdaget aktivitet i plasma som er vgll3a genotype avhengig er det sannsynlig at vi i videre studier kan finne en biomarkør i plasma som indikerer sein eller tidlig modning. Samlet sett har dette prosjektet brukt fire forskjellige banebrytende tilnærminger; genredigering, cellekulturer og proteomikk i kombinasjon med ex vivo vevskulturer, og morfologiske og fysiologiske analyser av genredigeringsassosierte fenotyper. Derfor har dette prosjektet avslørt mulige mekanismer som styrer tidspunktet for kjønnsmodning, ved å belyse molekylære funksjoner av Vgll3a-proteinet i laks.

This project will elucidate the link between the genetic prerequisite for age at maturation and how environmental cues can modulate or overrun this trait. Recent simultaneous publications by our group and others show that one single locus can largely determine sea age at maturation in Atlantic salmon. This has opened a door to directly investigate the link between the genetic and the epigenetic/environmental regulation of the age at maturity trait in salmon. Understanding the age of maturation trait in salmon is a pre-requisite for sustainable farming; early maturation causes significant impacts on: (i) fish welfare through increased susceptibility to disease and hypo-osmoregulatory problems in sea cages; (ii) production losses caused by mortality, impaired growth, and down-grading at harvest; (iii) genetic interactions with wild fish, since escaped early maturing fish have a lower risk for mortality before succeeding to spawn. We recently described a selective sweep locus which strongly influences sea age at maturity, which encodes three genes, with the vgll3 gene showing the strongest signature of selection. However, the causative genetic variant(s) at this locus are unknown. This project aims to find the causative variant and link this/these genetic variants to either protein function or gene expression control. To implement this idea, this project will (1) perform experiments with clonal salmon lines displaying several combinations of putative causative SNPs, (2) examine in-between species conservation and (3) perform functional studies in salmon and zebrafish. In addition, this project will elucidate effects of environmental factors and how these epigenetic mechanisms can modulate the genetic predisposition for age at maturity. The results of this project will contribute to more precise selection protocols for salmon.