The vgll3 Locus Controls Age at Maturity in Wild and Domesticated Atlantic Salmon (Salmo salar L.) Males

Abstract

Wild and domesticated Atlantic salmon males display large variation for sea age at sexual maturation, which varies between 1-5 years. Previous studies have uncovered a genetic predisposition for variation of age at maturity with moderate heritability, thus suggesting a polygenic or complex nature of this trait. The aim of this study was to identify associated genetic loci, genes and ultimately specific sequence variants conferring sea age at maturity in salmon. We performed a genome wide association study (GWAS) using a pool sequencing approach (20 individuals per river and phenotype) of male salmon returning to rivers as sexually mature either after one sea winter (2009) or three sea winters (2011) in six rivers in Norway. The study revealed one major selective sweep, which covered 76 significant SNPs in which 74 were found in a 370 kb region of chromosome 25. Genotyping other smolt year classes of wild and domesticated salmon confirmed this finding. Genotyping domesticated fish narrowed the haplotype region to four SNPs covering 2386 bp, containing the vgll3 gene, including two missense mutations explaining 33-36% phenotypic variation. A single locus was found to have a highly significant role in governing sea age at maturation in this species. The SNPs identified may be both used as markers to guide breeding for late maturity in salmon aquaculture and in monitoring programs of wild salmon. Interestingly, a SNP in proximity of the VGLL3 gene in humans (Homo sapiens), has previously been linked to age at puberty suggesting a conserved mechanism for timing of puberty in vertebrates.

Fig 1. Geographical location of salmon rivers used.

Map of Norway and a magnification of Western Norway showing rivers used in the experiment including three rivers in Sogn og Fjordane county; Eidselven, Gloppenelven and Flekkeelven, and three rivers in Rogaland county; Suldalslågen, Vormo and Årdalselven. Derivative of https://commons.wikimedia.org/wiki/File:Norway_municipalities_2012_blank.svg, licensed with CC-BY-SA-2.0.

Fig 2. Identification of a selective region conferring age at maturity in Atlantic salmon.

(A) Manhattan plot of SNPs associated with age at maturity. The x-axis presents genomic coordinates along chromosomes 1–29 in Atlantic salmon. On the y-axis the negative logarithm of the SNPs associated p-value is displayed. All SNPs above the solid horizontal line in the plot are significantly (p < 5.2e^-8, 0.1% FDR) associated with the trait. (B) Magnification of the 370kb region showing only 230 kb of the region on Chr 25 (28550–28780 kb) including 62 significant SNPs. The SNPs are represented by black dots, where the 11 large dots indicate SNPs used in genotyping assays. The square dots indicate three missense mutations in vgll3 and akap11. On the upper y-axis the negative logarithm of the SNPs associated p-value is displayed. The dashed line within the plot indicates the significance threshold (0.1% FDR). Below the SNP illustration, the lower y-axis shows average read depth of coverage (using 2 kb windows). Genomic organization of the three genes found in the region is illustrated in the bottom track. The x-axis shows the location of the region in Chr 25 and covers 28550–28780 kb. The grey area around vgll3 demarcates the shorter region discovered in the domesticated strain. The dark grey area in the coverage track is showing the misplaced contig in the most recent salmon genome release containing exon 1 and 2 of chmp2b.

Fig 3. Haplotype frequencies in different year classes in wild and domesticated salmon.

(A) Haplotype frequency associated with either 1SW (black bars) or 3SW (dark grey bars) in male Atlantic salmon for six rivers in Western Norway from year class 2008. (B) Haplotype frequencies associated with either 1SW (black bars) or 3SW (dark grey bars) male Atlantic salmon in year classes 1999 from Eidselva and 2004 from Suldalslågen. (C) Haplotype frequencies linked to age at maturity in the domesticated Mowi strain maturing after 1 (black bars), 2 (grey bars) or ≥ 3 (dark grey bars) years in sea water. In all graphs the x-axis indicates frequency of that trait for the identified haplotype, while the y-axis presents the haplotype block obtained from the genotype assay. * Indicates that the haplotype was significantly linked to the trait. The bold bases in the haplotypes are indicating missense mutations.