Functional differences between TSHR alleles associate with variation in spawning season in Atlantic herring

Abstract

The underlying molecular mechanisms that determine long day versus short day breeders remain unknown in any organism. Atlantic herring provides a unique opportunity to examine the molecular mechanisms involved in reproduction timing, because both spring and autumn spawners exist within the same species. Although our previous whole genome comparisons revealed a strong association of TSHR alleles with spawning seasons, the functional consequences of these variants remain unknown. Here we examined the functional significance of six candidate TSHR mutations strongly associated with herring reproductive seasonality. We show that the L471M missense mutation in the spring-allele causes enhanced cAMP signaling. The best candidate non-coding mutation is a 5.2 kb retrotransposon insertion upstream of the TSHR transcription start site, near an open chromatin region, which is likely to affect TSHR expression. The insertion occurred prior to the split between Pacific and Atlantic herring and was lost in the autumn-allele. Our study shows that strongly associated coding and non-coding variants at the TSHR locus may both contribute to the regulation of seasonal reproduction in herring.

Adaptation to seasonal reproduction and environment‐associated factors drive temporal and spatial differentiation in northwest Atlantic herring despite gene flow

“…In the case of Atlantic herring, we observe such genomic heterogeneity between spawning ecotypes (Han et al., 2020). Indeed, the 120 kb tshr locus has the strongest association with reproductive seasonality, as it shows substantial genetic differences between spring‐ and autumn‐spawning herring across the North Atlantic and Baltic Sea (Chen et al., 2021; Lamichhaney et al., 2017). Differences in breeding time (reproductive allochrony) can potentially constitute barriers to gene flow leading to reproductive isolation and population divergence (Taylor & Friesen, 2017).…”

Epigenetic patterns in Atlantic herring (Clupea harengus): Temperature and photoperiod as environmental stressors during larval development

“…Importantly, our study examined changes in gene activity at the methylation level, but photoperiod may affect gene expression at different levels such as at the genetic (i.e. TSHR gene; Fuentes‐Pardo et al., 2023; Chen et al., 2021) or transcriptomic level.…”

Non-synonymous variation and protein structure of candidate genes associated with selection in farm and wild populations of turbot (Scophthalmus maximus)

“…TSHR plays an important role in seasonal reproduction through the conserved EYA3-TSH pathway 106,107 . Polymorphisms in herring TSHR were shown to contribute to the regulation of spring or autumn spawning 36 , while the Leu339Glu polymorphism in turbot TSHR is positioned in a flexible region. Such intrinsically disordered regions are common in eukaryotic proteins and important biological functions have been associated with them, such as flexible linker, cellular signal transduction, protein phosphorylation 108,109 .…”

“…In Atlantic salmon ( Salmo salar ), non-synonymous SNPs in two strong candidate genes coding for the epithelial cadherin and the NEDD-8 activating enzyme 1 (NAE1) 33 , 34 have been suggested to be responsible for resistance to infectious pancreatic necrosis virus. Differences in spawning time associated with functionally different protein variants have been documented in Atlantic salmon vestigial-like protein 3 (VGLL3) and in herring ( Clupea harengus ) thyrotropin receptor (TSHR) 35 , 36 . A hemoglobin polymorphism in turbot was reported to be associated with differences in juvenile growth rates 37 , 38 and the underlying amino acid substitution was predicted to influence the stability of the oxygen-binding protein 39 .…”