Identification and characterization of coding and noncoding TSHR polymorphisms affecting photoperiodic regulation of reproduction in Atlantic herring

Spring- and autumn-spawning are different reproductive strategies in the Atlantic herring. thyroid stimulating hormone receptor (TSHR) is the most strongly associated locus underlying photoperiodic regulation of reproduction in this species. Here we have examined six candidate causal mutations showing the most consistent association with spawning time across populations. We show that the derived L471M missense mutation in the TSHR spring allele causes enhanced constitutive cAMP signaling providing evidence for its functional significance. The best candidate non-coding mutation is a 5.2 kb insertion/deletion polymorphism involving a BEL/Pao retroviral element located 2.15 kb upstream of the TSHR transcription start sites and in the near vicinity of an open chromatin region detected with ATAC-sequencing. The insertion happened prior to the divergence between Pacific and Atlantic herring and was subsequently deleted in the autumn allele. Our results suggest that coding and noncoding variants at the TSHR locus affect photoperiodic regulation of seasonal reproduction in Atlantic herring.