Biology subjects

Knutsen, T. M.

Publications and source records attributed to Knutsen, T. M..

6 recordsLinked to original sources

bioRxiv2025

A major QTL for resistance against Salmonid Rickettsial Septicaemia in coho salmon (Oncorhynchus kisutch) maps to a narrow region on chromosome 21, implicating two candidate genes

The facultative intracellular bacterium Piscirickettsia salmonis causes Salmon Rickettsial Syndrome (SRS) in Coho salmon, Atlantic salmon, and other salmonids. SRS causes large mortalities in Chilean aquaculture and leads to heavy usage of antibiotics. In Atlantic salmon SRS resistance is a polygenic trait with moderate to large heritability. In coho salmon a large QTL for SRS-resistance was earlier found on chromosome 21. In the present study we have further characterized genetic resistance to SRS in coho salmon and searched for putative candidate genes underlying the QTL. The mean heritability of survival was 0.31 and 0.58 on the observed and liability scale, respectively. The QTL on chromosome 21 explained from 26% to 97% of genetic variation within 12 different datasets. Two SNPs were substantially more significant compared to other SNPs and in very strong linkage disequilibrium with each other. The resistance allele was found to be dominant over the susceptibility allele at these SNPs. One of the two SNPs was located within the first exon of two genes which are transcribed in opposite directions: a histidine triad nucleotide-binding protein 3 (hint3) gene and a gene (LOC109866666) encoding a long non-coding RNA (lncRNA). Genotypes at the SNP were correlated with expression levels at both hint3 and the lncRNA gene, and the differential expression was manifested in both SRS-challenged and non-challenged fish. The exonic SNP is located 3 base pairs upstream of the start codon of the hint3 gene, at a position which is crucial for effective translation according to the rules of Kozak. The resistance allele at the SNP correlates to increased expression levels and increased translation levels at hint3, although the latter remains to be experimentally proven. Thus, it seems plausible that the QTL is due to the action of the hint3 gene and/or the gene lncRNA gene encoded by LOC109866666. The hint3 gene on chromosome 21 is different from homologs in Atlantic salmon, and no Atlantic salmon homologs of LOC109866666 were found. Thus, it might be possible to increase SRS-resistance of Atlantic salmon by inserting the coho gene(s) through gene editing.

genomics↗

bioRxiv2025

Phenotypic sex determines recombination rate and distribution in sex-reversed Rainbow Trout Oncorhynchus mykiss

During meiotic cell division, homologous chromosomes align and exchange large segments of DNA through crossover recombination. Rates of recombination often show distinct differences between males and females, a phenomenon known as heterochiasmy. Despite decades of research documenting the presence of heterochiasmy across eukaryotes, the specific feature of sex leading to this curious sexual dimorphism remains to be explained. Some species, such as salmonids, also display extensive differences between the sexes in crossover positioning. A critical part of solving this puzzle is to establish whether heterochiasmy is driven by genetic sex or if it is a result of the physiological differences between producing sperm and eggs. In this study, we show that phenotypic sex determines recombination rate and distribution in hormonally sex-reversed rainbow trout. With pedigree and genotype information from 18 452 individuals and 33 913 SNP markers we map crossover events in families where the fathers were hatched as genetic XX females and sex-reversed as young trout fry with a masculinising hormone 17-methyltestosterone and compare the crossover patterns to those in families with normal XY male fathers. We find that recombination patterns in XX males resemble those of normal XY males with crossovers exclusively in sub-telomeric regions. Crossover count per gamete was 25.8{+/-}4.4 in XX females vs 19.5{+/-}3.9 and 19.9{+/-}4.0 in XY males and XX males, respectively. These results support the hypothesis that heterochiasmy arises from physiological differences between oogenesis and spermatogenesis rather than effects related to genetic sex and will aid in guiding the research on heterochiasmy going forward.

genetics↗

bioRxiv2025

Sequence-based chromatin activity modeling and regulatory impact prediction of genetic variants in farmed animals using deep learning

Non-coding genomic variations are crucial for the genetic regulation of traits; how-ever, their functional impact in farmed animals remains underexplored due to lim-ited genomic resources and the absence of tailored computational tools. Here, we present a deep learning-based framework that utilizes functional genomics data to generate genome-wide predictions of the regulatory impact of non-coding vari-ants in cattle, chicken, pig, and Atlantic salmon. By leveraging chromatin profiles such as ATAC, DHS, and ChIP-seq data, we train and optimize separate deep networks for each species, achieving robust sequence modeling accuracy specific to each. Motif analysis confirms that the models capture regulatory grammar, while in silico saturation mutagenesis experiments provide meaningful interpretations of the functional impact of putative causal variants. Furthermore, functional scores derived from these models predict eQTL causal variants and enhance genomic prediction performance. Our findings highlight the transformative potential of se-quence to function models in prioritizing causal variants and improving genomic prediction for livestock and aquaculture.

genomics↗

bioRxiv2023

Linking genomic prediction for muscle fat content in Atlantic salmon to underlying changes in lipid metabolism regulation

Muscle fat content is an important production trait in Atlantic salmon (Salmo salar) because it influences the flavor, texture, and nutritional properties of the fillet. Genomic selection can be applied to alter muscle fat content, however how such selection changes the underlying molecular physiology of these animals is unknown. Here, we examine the link between genomic prediction and underlying molecular physiology by correlating genomic breeding values for fat content to liver gene expression in 184 fish. We found that Salmon with higher genomic breeding values had higher expression of genes in lipid metabolism pathways. This included key lipid metabolism genes hmgcrab, fasn-b, fads2d5, and fads2d6, and lipid transporters fatp2f, fabp7b, and apobc. We also found several regulators of lipid metabolism with negative correlation to genomic breeding vales, including pparg-b, fxr-a, and fxr-b. A quantitative trait loci analysis for variation in gene expression levels (eQTLs) for 167 trait associated genes found that 71 genes had at least one eQTL, and that most were trans eQTLs. Closer examination revealed distinct eQTL clustering on chromosomes 3 and 6, indicating the presence of putative common regulator in these regions. Taken together, these results suggest that increased fat content in high genomic breeding value salmon is associated with elevated lipid synthesis, elevated lipid transport, and reduced glycerolipid breakdown; and that this is at least partly achieved by selection on genetic variants that impact the function of top-level transcription factors involved in liver metabolism. Our study sheds light on how genomic selection alters lipid content in Atlantic salmon, and the results could be used to prioritize SNPs to improve the efficiency of genomic selection in the future.

genomics↗

bioRxiv2023

Genetic architecture of individual meiotic crossover rate and distribution in a large Atlantic Salmon (Salmo salar) breeding population.

Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes in meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in >5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6x higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8x higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h2 = 0.11) and males (h2 = 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h2 = 0.06) than in males (h2 = 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.

genetics↗

bioRxiv2021

SmdA is a novel cell morphology determinant in Staphylococcus aureus

Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining their nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied intensively, however, hitherto unknown factors and proteins are likely to play key roles in this complex interplay. We here identified and investigated a protein with major influence on cell morphology in Staphylococcus aureus. The protein, named SmdA (for staphylococcal morphology determinant A), is a membrane-protein with septum-enriched localization. By CRISPRi knockdown and overexpression combined with different microscopy techniques, we demonstrate that proper levels of SmdA is necessary for cell division, including septum formation and cell splitting. We also identified conserved residues in SmdA that are critical for its functionality. Pulldown- and bacterial two-hybrid interaction experiments showed that SmdA interacts with several known cell division- and cell wall synthesis proteins, including penicillin binding proteins (PBPs) and EzrA. Notably, SmdA also affects susceptibility to cell wall targeting antibiotics, particularly in methicillin-resistant S. aureus (MRSA). Together, our results show that S. aureus is dependent on balanced amounts of membrane-attached SmdA in order to carry out proper cell division. ImportanceStaphylococcus aureus is an important human and animal pathogen. Antibiotic resistance is a major problem in treatment of staphylococcal infections, and cell division and cell wall synthesis factors have previously been shown to modulate susceptibility to antibiotics in this species. In the current work we investigated the function of an essential protein named SmdA, which was identified based on its septal localization and knockdown phenotype resulting in defective cellular morphologies. We demonstrate that this protein is critical for normal cell division in S. aureus. Depletion of SmdA sensitize resistant staphylococci to {beta}-lactam antibiotics. This work thus reveals a new staphylococcal cell division factor and a potential future target for narrow spectrum antimicrobials or compounds to resensitize antibiotic resistant staphylococcal strains.

microbiology↗