Biology subjects

Sinclair-Waters, M.

Publications and source records attributed to Sinclair-Waters, M..

6 recordsLinked to original sources

bioRxiv2022

A pituitary gene network linking vgll3 to regulators of sexual maturation in male Atlantic salmon

Age at maturity is a key life history trait and a significant contributor to life history strategy variation. The maturation process is complex and influenced by genetic and environmental factors alike, but specific causes of variation in maturation timing remain elusive. In many species, the increase in the regulatory gonadotropin-releasing hormone 1 (GnRH1) marks the onset of puberty. Atlantic salmon, however, lack the gene encoding GnRH1, suggesting other regulatory factors are involved in the maturation process. Earlier research in Atlantic salmon has found a strong association between alternative alleles of vgll3 and maturation timing, making vgll3 a candidate reproductive axis gene regulator. Recently we reported strong induction of gonadotropin encoding genes (fshb and lhb) in the pituitary of male Atlantic salmon homozygous for the vgll3 allele linked with the early maturation allele (E). The induction of gonadotropins was accompanied by increased expression of their direct upstream regulators, c-jun and sf1 (nr5a1b) in the pituitary. In mammals, the transcriptional activation of c-jun and sf1 is also required for induction of fshb and lhb, however, GnRH1 is responsible for increased transcriptional activity of c-jun and sf1. The absence of gnrh1 in salmon raises the possibility of the involvement of other regulators upstream of these factors. In this study, we investigated such a possibility through a stepwise approach for identifying a gene regulatory network (GRN) containing c-jun and sf1 and using the zebrafish coexpression database and transcription factor motif enrichment analysis. We found a GRN containing c-jun with predicted upstream regulators, e2f1, egr1, foxj1 and klf4, which are also differentially expressed in the pituitary. Finally, we suggest a model for transcriptional regulation of c-jun and sf1in the absence of gnrh1 in the pituitary, which may have broader implications across vertebrates.

molecular biology↗

bioRxiv2021

Life-history genotype explains variation in migration activity in Atlantic salmon (Salmo salar).

One of the most important life-history continuums is the fast-slow axis, where "fast" individuals mature earlier than "slow" individuals. "Fast" individuals are predicted to be more active than "slow" individuals; high activity is required to maintain a fast life-history strategy. Recent meta-analyses revealed mixed evidence for such integration. Here, we test whether known life-history genotypes differ in activity expression by using Atlantic salmon (Salmo salar) as a model. In salmon, variation in Vgll3, a transcription co-factor, explains [~]40% of variation in maturation timing. We predicted that the allele related to early maturation (vgll3*E) would be associated with increased activity. We used an automated surveillance system to follow [~]1900 juveniles including both migrants and non-migrants (i.e. smolt and parr fish, respectively) in semi-natural conditions over 31 days ([~]580 000 activity measurements). Against our prediction, vgll3 did not explain variation in activity in pooled migrant and non-migrant data. However, in migrants, vgll3 explained variation in activity according to our prediction in a sex-dependent manner. Specifically, in females the vgll3*E allele was related to increasing activity, whereas in males the vgll3*L allele (later maturation allele) was related to increasing activity. These sex-dependent effects might be a mechanism maintaining within-population genetic life-history variation.

evolutionary biology↗

bioRxiv2021

Strong regulatory effects of vgll3 genotype on reproductive axis gene expression in immature male Atlantic salmon

Age at maturity is a major contributor to the diversity of life history strategies in organisms. The process of maturation is influenced by both genetics and the environment, and includes changes in levels of sex hormones and behavior, but the specific factors leading to variation in maturation timing are not well understood. gnrh1 regulates the transcription of gonadotropin genes at the onset of puberty in many species, but this gene is lacking in certain teleost species including Atlantic salmon (Salmo salar), which raises the possibility of the involvement of other important regulatory factors during this process. Earlier research has reported a strong association of alternative alleles of the vgll3 gene with maturation timing in Atlantic salmon, suggesting it as a potential candidate regulating reproductive axis genes. Here, we investigated the expression of reproductive axis genes in immature Atlantic salmon males with different vgll3 genotypes during the spawning period. We detected strong vgll3 genotype-dependent differential expression of reproductive axis genes (such as fshb, lhb, amh and igf3) tested in the pituitary, and testis of one-year-old immature male Atlantic salmon. In addition, we observed differential expression of jun (ap1) and nr5a1b (sf1), potential upstream regulators of gonadotropins in the pituitary, as well as axin2, id3, insl3, itch, ptgs2a and ptger4b, the downstream targets of amh and igf3 in the testis. Hereby, we provide evidence of strong vgll3 genotype-dependent transcriptional regulation of reproductive axis genes prior to sexual maturation together with models for distinct actions of vgll3 genotypes on the molecular processes controlling spermatogenesis in Atlantic salmon.

physiology↗

bioRxiv2021

Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods

Resolving the genetic architecture of fitness-related traits is key to understanding the evolution and maintenance of fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to further characterize known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci (on chromosomes ssa06, ssa09, ssa21, and ssa25) out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at each of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of Atlantic salmon maturation includes multiple loci with simple, non-clustered alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations.

evolutionary biology↗

bioRxiv2021

Refining the genomic location of SNP variation affecting Atlantic salmon maturation timing at a key large-effect locus

Efforts to understand the genetic underpinnings of phenotypic variation are becoming more and more frequent in molecular ecology. Such efforts often lead to the identification of candidate regions showing signals of association and/or selection. These regions may contain multiple genes and therefore validation of which genes are actually responsible for the signal is required. In Atlantic salmon (Salmo salar), a large-effect locus for maturation timing, an ecologically important trait, occurs in a genomic region including two genes, vgll3 and akap11, but data for clearly determining which of the genes (or both) contribute to the association have been lacking. Here, we take advantage of natural recombination events detected between the two candidate genes in a salmon broodstock to reduce linkage disequilibrium at the locus, and thus enabling delineation of the influence of variation at these two genes on maturation timing. By rearing 5895 males to maturation age, of which 81% had recombinant vgll3/akap11 allelic combinations, we found that vgll3 SNP variation was strongly associated with maturation timing, whereas there was little or no association between akap11 SNP variation and maturation timing. These findings provide strong evidence supporting vgll3 as the primary candidate gene in the chromosome 25 locus for influencing maturation timing. This will help guide future research for understanding the genetic processes controlling maturation timing. This also exemplifies the utility of natural recombinants to more precisely map causal variation underlying ecologically important phenotypic diversity.

genetics↗

bioRxiv2018

A migration-associated supergene reveals loss of biocomplexity in Atlantic cod

Intraspecific phenotypic diversity is integral to ecological resilience and the provision of ecosystem services1. Chromosome structural variation may underpin intraspecific diversity and complex phenotypes2 by reducing recombination within supergenes containing linked, co-adapted alleles. Connecting ecologically-relevant phenotypes to genomic variation can enable more precise conservation of exploited marine species by protecting important genetic diversity3,4. Here, using genome-wide association analysis of a 12K single nucleotide polymorphism (SNP) array we confirm that an ancient, derived chromosomal rearrangement consisting of two adjacent inversions is strongly associated with migratory phenotype and individual-level genetic structure in Atlantic cod (Gadus morhua) across the Northwest Atlantic. The presence of all identified migration-associated loci within this rearrangement indicates that pervasive variation in migration phenotype is in part controlled by a recombination-resistant supergene, facilitating fine-scale individual phenotypic variation within Northern cod. Furthermore, we reconstruct trends in effective population size over the last century, and find genomic signatures of population collapse, and different patterns of population expansion and decline among individuals based on supergene alleles. We demonstrate declines in effective population size consistent with the onset of industrialized harvest (post 1950) and substantially reduced effective size of individuals homozygous for the derived chromosomal rearrangement relative to heterozygous individuals or those homozygous for the ancestral version of this chromosomal region. These results illustrate how chromosomal structural diversity can mediate fine-scale genetic and phenotypic variation in a highly connected marine species, and suggest a loss of biocomplexity from a migration-associated supergene within Northern cod by overfishing.

genomics↗