Biology subjects

Knutsen, T. M.

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

3 recordsLinked to original sources

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↗