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

Junfeng Chen,Shady Younis,Ana Gómez,Patric Jern,Huijuan Bi,Mats E Pettersson,Ola Wallerman,Patrick Scheerer,Gunnar Kleinau,Angela P Fuentes-Pardo,Leif Andersson,Daiki X Sato,Gregorio Molés,Chunheng Mo

doi:10.1038/s42003-021-02307-7

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.

Highlights

The underlying molecular mechanisms that determine long day versus short day breeders remain unknown in any organism
The data were consistent with the presence of selective sweeps at the TSH receptor (TSHR) locus in both autumn- and spring-spawning herring as the nucleotide diversities are significantly lower in the TSHR region than they are in the rest of the genome (Fig. 1c)
Previous population studies in Atlantic herring have documented that TSHR is clearly the most strongly differentiated locus between spring and autumn spawners in West-Atlantic, EastAtlantic and Baltic Sea populations[15,17,26,27]

Summary

Introduction

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. Atlantic herring (Clupea harengus) is one of the most abundant fish species on Earth[13] and exhibits seasonal reproduction predominantly in spring and autumn. This species provides a unique opportunity to dissect the mechanisms controlling timing of reproduction due to the variation within species rather than between species which allow powerful genetic analysis. We show using mutagenesis and transfection experiments that the L471M substitution in the spring-allele results in enhanced constitutive cAMP signaling, and the 5.2 kb retrotransposon variant upstream of TSHR near an open chromatin region may affect TSHR expression

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Conclusion