Biology subjects

Ruokolainen, A.

Publications and source records attributed to Ruokolainen, A..

11 recordsLinked to original sources

bioRxiv2025

Testicular gene expression patterns suggest a heterochronic shift underlying vgll3-mediated maturation age variation in Atlantic salmon

Heterochrony, or shifts in developmental timing, drives phenotypic diversity within and between species and shapes life history traits that can be selected for in changing environments which in turn promotes population resilience. Despite its importance, the molecular basis of heterochrony remains largely unknown. Mutations in "heterochronic genes" that regulate these processes can induce stable timing shifts, impacting important life history traits like pubertal timing. Heterochronic shifts in gene transcription are often tissue-specific and in mammals, for example, the testis shows the most pronounced heterochrony across species, especially during spermatogenesis. Age at maturity is a key adaptive trait across species, with vgll3, a Hippo pathway co-factor, as a main determinant in Atlantic salmon. The roles of vgll3 in maturation timing, adiposity, and energy storage are evolutionarily conserved across fish and mammals. Recent studies in salmon show vgll3 alleles; early (E) and late (L), affect reproductive gene expression, reinforcing its role in regulating developmental timing. This study examines whether vgll3 influences testicular heterochrony in Atlantic salmon by analyzing Hippo pathway-related gene expression in E and L genotypes. We observed heterochronic divergence in Hippo pathway gene transcription, indicating accelerated spermatogenesis-linked changes in the testes of vgll3*EE individuals. Since maturation in Atlantic salmon is closely tied to environmental changes, and the Hippo pathway acts as an environmental sensor, these findings suggest that Hippo-vgll3 shifts may also respond to environmental signals. This positions vgll3 as a heterochronic gene which is potentially affected by environmental changes (heterokairic), making it an ideal target for studying ecological adaptation linked to heterochrony.

developmental biology↗

bioRxiv2024

Hippo-vgll3 signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics

Sexual maturation in Atlantic salmon entails a transition in energy utilization, governed in part by genes and environmental stimuli in sex-specific manner. Salmon males require less energy, in the form of adiposity, to mature compared to females and typically mature younger. Maturation age is also influenced in a sex-dependent fashion by the vgll3 genotype (vestigial-like 3), a co-factor in the Hippo pathway. The underlying molecular processes of sex-dependent maturation age, and how they interplay with adiposity and vgll3 genotypes, have remained unknown. To elucidate the molecular mechanisms underlying sex- and genotype-specific maturation differences, we investigated the association of early (E) and late (L) maturation vgll3 alleles and the transcriptional expression of > 330 genes involved in the regulation of the Hippo pathway and sexual maturation, and related to molecular signals in brain, adipose tissue, and gonads. The strongest effect of vgll3 genotype was observed in adipose tissue for females and in brain for males, highlighting a sex-specific expression difference in the main association of vgll3 genotype. Genes related to ovarian development showed increased expression in vgll3*EE compared to vgll3*LL females. Additionally, vgll3*EE females compared to vgll3*EE males exhibited reduced markers of pre-adipocyte differentiation and lipolysis yet enhanced expression of genes related to adipocyte maturation and lipid storage. Brain gene expression further showed sex-specific expression signals for genes related to hormones and lipids, as well as tight junction assembly. Overall, these sex-specific patterns point towards a greater lipid storage and slower energy utilization in females compared to males. These results suggest that Hippo-dependent mechanisms may be important mediators of sex differences in maturation age in salmon.

genetics↗

bioRxiv2024

Sex-, development-, and nutrition-dependent expression of a major age-at-maturity gene in Atlantic salmon

Sexual maturation is a key process in the life history of an organism and is influenced by both genetic and environmental factors. In Atlantic salmon (Salmo salar), alternative alleles at the gene vgll3 have been found to associate with a large proportion of the variation in maturation age, yet the molecular and physiological mechanisms of this association are still largely unknown. Here, we investigated the mechanisms by which genetic variation in this major age-at-maturity gene translated into phenotypic variation. We established a time series of gonadal vgll3 mRNA expression in male and female Atlantic salmon in a common garden setting, starting at the prepubertal stage and spanning multiple spawning seasons. We found that vgll3 mRNA expression is reduced in early-maturing males and females. However, for the second spawning season, vgll3 expression increased with gonadal development in males, but eventually decreased in females. Expression of vgll3 had context-dependent correlations with expression of amh and lhr. We also found signs of reduced testicular vgll3 expression in a low-fat feed treatment. By significantly widening the scope of our knowledge on temporal vgll3 expression dynamics, our results exemplify that major-effect genes may use different pathways in sexes but achieve similar outcomes.

genetics↗

bioRxiv2024

A salmon fish model reveals genetic signals in brain associated with early maturation

Emerging evidence suggests a link between adiposity and early maturation, potentially impacting hormonal signaling pathways governing puberty timing. Fish models have proven invaluable in studying these processes, given their genetic and physiological similarities to humans. In Atlantic salmon, in addition to being linked with environmental shifts and lipid reserves, the timing of sexual maturation also has a strong genetic basis. A gene encoding a co-factor of Hippo pathway, vgll3, is a major determinant of maturation timing in salmon, and the same gene was found to be associated with maturation timing in humans. Intriguingly, vgll3 also inhibits adipogenesis in mice. Recent studies in salmon revealed correlations between vgll3 genotypes and reproductive axis gene expression, possibly modulated through the Hippo signaling pathway. The Hippo pathway is known for its role in sexual maturation and adipogenesis and responds to environmental cues such as dietary fat and temperature. In this study, we employed a custom gene expression panel in male Atlantic salmon with different vgll3 early (E) and late (L) maturation genotypes testing components of this pathway in brain at immature and mature stages. We found increased brain expression of a major Hippo pathway kinase (lats1b) and melanocortin receptor encoding genes (mc4ra and mc4rc) in individuals with early (E) maturation genotypes of vgll3 before maturation development of testes. Moreover, we found components and interacting partners of Hippo pathway showing differential expression in brain of individuals with early (E) and late (L) vgll3 genotypes prior to maturation. This could indicate extensive and complex roles of Hippo pathway in brain processes required for preparing for [the onset of] maturation at upstream of reproductive axis. This study elucidates molecular mechanisms underpinning early maturation, and for the first time in fish, offering insights into detecting it at molecular level in brain before visible gonadal changes occur.

genetics↗

bioRxiv2024

A complex mechanism translating variation of a simple genetic architecture into alternative life-histories

Linking genes to traits is a central goal in biology. Despite progress in discovering genes associated with trait differences, a poor understanding of the functional mechanisms underlying genetic associations leaves us critically far from connecting genetic and phenotypic variation. This knowledge-gap is particularly large in multifaceted phenotypes of ecological relevance such as life-history traits. Using a multiomic dissection of the genotype-phenotype association in a large-effect maturation age gene - the transcription cofactor vestigial-like 3 (vgll3) - in Atlantic salmon (Salmo salar), we show that vgll3 mediates concerted changes of distinct molecular phenotypes associated with puberty in male gonads. Vgll3 genotype conferring early maturity upregulates key genes controlling androgen production, cellular energy and adiposity, and TGF-{beta} signaling, among others, thereby increasing the likelihood of earlier pubertal initiation. Genotype-dependent developmental trajectories are produced through VGLL3 interaction with distinct transcription factors, thus coordinating differential activation of regulatory pathways. These results reveal a genetically simple, yet functionally complex, architecture underlying alternative life-histories where variation in a single major effect gene produces pleiotropic variation in a spectrum of cellular traits. Our results further suggest that evolution in correlated phenotypes such as exemplified by alternative life history strategies may be mediated by a surprisingly simple genetic architecture.

evolutionary biology↗

bioRxiv2023

Gene co-expression patterns in Atlantic salmon adipose tissue provide a molecular link between seasonal changes, energy balance and age at maturity

Sexual maturation in many fishes requires a major physiological change that involves a rapid transition between energy storage and usage. In Atlantic salmon, this transition for the initiation of maturation is tightly controlled by seasonality and requires a high-energy status. Lipid metabolism is at the heart of this transition since lipids are the main energy storing molecules. The balance between lipogenesis (lipid accumulation) and lipolysis (lipid use) determines energy status transitions. A genomic region containing a transcription co-factor of the Hippo pathway, vgll3, is the main determinant of maturation timing in Atlantic salmon. Interestingly, vgll3 acts as an inhibitor of adipogenesis in mice and its genotypes are potentially associated with seasonal heterochrony in lipid storage and usage in juvenile Atlantic salmon. Here, we explored changes in expression of more than 300 genes directly involved in the processes of adipogenesis, lipogenesis and lipolysis, as well as the Hippo pathway in the adipose tissue of immature and mature Atlantic salmon with distinct vgll3 genotypes. We found molecular evidence consistent with a scenario in which immature males exhibiting vgll3 genotype specific seasonal direction of change in their lipid profiles. We also identified components of the Hippo signaling pathway as potential major drivers of vgll3 genotype specific differences in adipose tissue gene expression. This study demonstrates the importance of adipose gene expression patterns for directly linking environmental changes with energy balance and age at maturity through genetic factors bridging lipid metabolism, seasonality and sexual maturation.

physiology↗

bioRxiv2021

Genetic coupling of life-history and aerobic performance in juvenile Atlantic salmon

A better understanding of the genetic and phenotypic architecture underlying life-history variation is a longstanding aim in biology. Theories suggest energy metabolism determines life-history variation by modulating resource acquisition and allocation trade-offs, but the genetic underpinnings of the relationship and its dependence on ecological conditions have rarely been demonstrated. The strong genetic determination of age-at-maturity by two unlinked genomic regions (vgll3 and six6) makes Atlantic salmon (Salmo salar) an ideal model to address these questions. Using more than 250 juveniles in common garden conditions, we quantified the covariation between metabolic phenotypes -standard and maximum metabolic rates (SMR and MMR), and aerobic scope (AS) - and the life-history genomic regions and tested if food availability modulates the relationships. We found that the early maturation genotype in vgll3 was associated with higher MMR and consequently AS. Additionally, MMR exhibited physiological epistasis; it was decreased when late maturation genotypes co-occurred in both genomic regions. Contrary to our expectation, the life-history genotypes had no effects on SMR. Further, food availability had no effect on the genetic covariation, suggesting a lack of genotype-by-environment interactions. Our results provide insights on the key organismal processes that link energy use at the juvenile-stage to age-at-maturity, indicating potential mechanisms by which metabolism and life-history can coevolve.

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↗

bioRxiv2020

Improved chromosome level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) based on SMRT Sequencing and linkage map.

The Glanville fritillary (Melitaea cinxia) butterfly is a long-term model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome level assembly of the butterflys genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO, indicates that the genome contains 93 - 95% of the BUSCO genes in complete and single copies. We predicted 14,830 gene models using the MAKER pipeline and manually curated 1,232 of these gene models. The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome and genetics studies on this species.

genomics↗

bioRxiv2019

Large single-locus effects for maturation timing are mediated via condition variation in Atlantic salmon

Maturation timing is a pivotal life-history trait balancing probabilities between mortality and reproduction. Environmental vs. genetic contributions to traits associated with maturation initiation, such as growth and body condition, remain uncertain because of difficulties in determining causality. In Atlantic salmon, maturation timing associates with a large-effect locus around vgll3, but how this locus affects maturation remains unknown. We combined controlled breeding with common-garden experimentation at two temperatures and show that vgll3 effects on maturation of males express primarily via body condition, which we demonstrate in the males non-maturing female relatives, thus avoiding reverse causality. Between homozygous vgll3 genotypes, maturation probability differed several folds and female condition differed 2% in both temperature environments. Vgll3 effects explained 25 and 16% of maturation probability heritability and 15 and 6% of female condition heritability, in the warm and cold environment, respectively. Non-significant vgll3 effects on female length were antagonistic to those on condition but of equal proportional size. When controlling for vgll3 effects, genetic correlations changed antagonistically between both maturation and condition vs. growth, suggesting vgll3 as a resource-allocation locus. The results support large vgll3 maturation effects being mediated via environmentally stable body condition effects, enabling rapid co-evolution between the life-history traits.

evolutionary biology↗

bioRxiv2019

Regulatory divergence in vgll3 underlies variation in age at maturity in male Atlantic salmon

A major goal in biology is to understand how evolution shapes variation in individual life histories. Genome-wide association studies have been successful in uncovering genome regions linked with traits underlying life history variation in a range of species. However, lack of functional studies of the discovered genotype-phenotype associations severely restrains our understanding how alternative life history traits evolved and are mediated at the molecular level. Here, we report a cis-regulatory mechanism whereby expression of alternative isoforms of the transcription co-factor vestigial-like 3 (vgll3) associate with variation in a key life history trait, age at maturity, in Atlantic salmon (Salmo salar). Using a common-garden experiment, we first show that vgll3 genotype associates with puberty timing in one-year-old salmon males. By way of temporal sampling of vgll3 expression in ten tissues across the first year of salmon development, we identify a pubertal transition in vgll3 expression where maturation coincided with a 66% reduction in testicular vgll3 expression. The late maturation allele was not only associated with a tendency to delay puberty, but also with expression of a rare transcript isoform of vgll3 pre-puberty. By comparing absolute vgll3 mRNA copies in heterozygotes we show that the expression difference between the early and late maturity alleles is largely cis-regulatory. We propose a model whereby expression of a rare isoform from the late allele shifts the liability of its carriers towards delaying puberty. These results reveal how regulatory differences can be a central mechanism for the evolution of life history traits. Author summaryAlternative life history strategies are an important source of diversity within populations and promote the maintenance of adaptive capacity and population resilience. However, in many cases the molecular basis of different life history strategies remains elusive. Age at maturity is a key adaptive life history trait in Atlantic salmon and has a relatively simple genetic basis. Using salmon age at maturity as a model, we report a mechanism whereby different transcript isoforms of the key age at maturity gene, vestigial-like 3 (vgll3), associate with variation in the timing of male puberty. Our results show how gene regulatory differences in conjunction with variation in gene transcript structure can encode for complex alternative life histories.

evolutionary biology↗