monica

• Hansen, Nina; Moberg, Ingrid Marie; Solbakken, Monica Hongrø; Gunnes, Gjermund; Borge, Kaja Sverdrup & Arnet, Ellen Frøysadal [Show all 9 contributors for this article] (2026). Expression of Estrogen Receptor Alpha and Ki-67 in Synchronous Canine Mammary Tumors. Journal of mammary gland biology and neoplasia. ISSN 1083-3021. 31(1). doi: 10.1007/s10911-026-09608-9. Full text in Research Archive
• Solbakken, Monica Hongrø; Tørresen, Ole Kristian; Tooming-Klunderud, Ave; Skage, Morten; Bakken, Torkild & Jakobsen, Kjetill Sigurd (2026). Loss of Major Histocompatibility Complex I and II Function in the Genome of Glacier Lanternfish Provides Insight Into Evolution of Vertebrate Immune Systems. Genome Biology and Evolution (GBE). 18(7). doi: 10.1093/gbe/evag154. Full text in Research Archive
• Moberg, Ingrid Marie; Hansen, Nina; Bergholtz, Helga; Borge, Kaja Sverdrup; Gunnes, Gjermund & Arnet, Ellen Frøysadal [Show all 9 contributors for this article] (2026). Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes. Veterinary and Comparative Oncology. ISSN 1476-5810. doi: 10.1111/vco.70067. Full text in Research Archive
• Ord, James; Martinez, Helena Saura; Solbakken, Monica Hongrø; Berezenko, Anastasiia; Oberhaensli, Simone & Talker, Stephanie [Show all 8 contributors for this article] (2026). Single-cell analysis of a salmonid immune system (river brown trout Salmo trutta fario) reveals evolutionary divergence and hatchery-induced transcriptional reprogramming. BMC Biology. 24(1). doi: 10.1186/s12915-026-02554-2. Full text in Research Archive Show summary

  Vertebrate immune systems exhibit striking evolutionary diversity, yet our understanding remains biased toward mammalian models. Here, we generate a single-cell transcriptome of immune cells from the ecologically and economically important salmonid Salmo trutta fario (river brown trout), a lineage characterized by an ancestral whole-genome duplication (WGD). Profiling over 83,000 kidney-derived immune cells, we resolved 34 transcriptionally distinct populations, identified core immune lineages, and uncovered novel markers in neutrophils, macrophages, T-cells, and B-cells. We detected pervasive transcriptional divergence between WGD-derived ohnologue pairs, indicating putative sub- and neofunctionalization in immune gene regulation. We further show that the transcriptional identity of immune cells is shaped by rearing history: fish raised in hatcheries—whether for one or multiple generations—showed shifts in immune gene expression across cell types. Our findings provide baseline data for the healthy brown trout cellular immune system, insight into the evolution of vertebrate immunity, and avenues for understanding the molecular basis of reduced immunological fitness of hatchery-reared fish.

• Solbakken, Monica Hongrø; Tørresen, Ole K.; Tooming-Klunderud, Ave; Skage, Morten; Bakken, Torkild & Jakobsen, Kjetill Sigurd (2025). The genome of the Glacier lanternfish shows loss of MHC I and II function and provides insight into evolution of lanternfish immune systems. bioRxiv - the preprint server for biology. doi: https:/www.biorxiv.org/content/10.1101/2025.08.28.672920v1. Full text in Research Archive Show summary

  Lanternfishes (Myctophidae) are one of the most abundant and species diverse orders inhabiting the mesopelagic zone. Exploitation of marine resources has recently attracted increased interest. It is therefore essential to improve our understanding of the meso- and deep pelagic ecosystems with respect to conservation and management strategies. Genomic resources are paramount to enable in-depth studies of population structuring and understanding the inherent genetic diversity, but also to enable studies of processes such as local adaptation and selection. Here we present a genome assembly of the Glacier lanternfish (Benthosema glaciale) generated with long-read PacBio and Hi-C contact map data. By comparing additional available genomes from the Myctophiformes order we explore their adaptive immune strategies. Our findings reveal that multiple lineages within this order have lost a significant proportion of genes related to adaptive immunity (Electrona, Protomyctophum and Benthosema). We find simultaneous loss of both classical MHC class I and class II function coinciding with reduction in genetic diversity with respect to immunoglobulin and T-cell receptors. In contrast, the sister branch represented by Gymnoscopelus and Nannobrachium appear to have maintained the standard configuration of the jawed vertebrate adaptive immune system apart from large gene expansions in MHC class II. Our results demonstrate that the Benthosema-belonging lineage (Myctophinae) has completely lost the core functions of the adaptive immune system. How, when and why this occurred warrants further investigations.

• Bjørnestad, Synne Arstad; Solbakken, Monica Hongrø; Krokene, Pia; Thiede, Bernd; Hylland, Ketil & Jakobsen, Kjetill Sigurd [Show all 9 contributors for this article] (2024). The Atlantic Cod MHC I compartment has the properties needed for cross-presentation in the absence of MHC II. Scientific Reports. 14(1). doi: 10.1038/s41598-024-76225-z. Full text in Research Archive Show summary

  Atlantic cod has a peculiar immune system, characterized by the loss of Major Histocompatibility Complex (MHC) class II pathway, and an extreme expansion of the MHC class I gene repertoire. This has led to the hypothesis that some of the MHC I variants have replaced MHC II by presenting exogenous-peptides in a process similar to cross-presentation. In mammals, MHC I loads endogenous antigens in the endoplasmic reticulum, but we recently found that different Atlantic cod MHC I gene variants traffic to endolysosomes. There, they colocalize with Tapasin and other components of the peptide-loading complex, indicating a plausible peptide-loading system outside the endoplasmic reticulum. In this study, we further characterize the identity of the Atlantic cod MHC I compartment (cMIC). We found that, similarly to mammalian MHC II compartment, cMIC contains late endosomal markers such as Rab7, LAMP1 and CD63. Furthermore, we identified Hsp90b1 (also known as grp94) and LRP1 (also known as CD91) as interactors of MHC I by mass spectrometry. As these two proteins are involved in cross-presentation in mammals, this further suggests that Atlantic cod MHC I might use a similar mechanism to present exogenous peptides, thus, compensating for the absence of MHC II.

• Bjørnestad, Synne Arstad; Solbakken, Monica Hongrø; Jakobsen, Kjetill Sigurd; Jentoft, Sissel; Bakke, Oddmund & Progida, Cinzia (2023). Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals. Frontiers in Cell and Developmental Biology. 11, p. 1–15. doi: 10.3389/fcell.2023.1050323. Full text in Research Archive Show summary

  Major histocompatibility complex (MHC) class I and II are crucial for the adaptive immune system because they are involved in peptide presentation to T cells. Until recently, it was believed that MHC genes and their associated immune components had been conserved since their evolutionary emergence in jawed fish. However, sequencing of the Atlantic cod ( Gadus morhua ) genome revealed a loss of MHC class II genes, and an extreme expansion of MHC class I genes. These findings lead to the hypothesis that a loss of the MHC class II pathway coincided with a more versatile use of MHC class I, but so far there is no direct experimental evidence in support of this. To gain a deeper understanding of the function of the expanded MHC class I, we selected five MHC class I gene variants representing five of the six clades identified in previous studies and investigated their intracellular localization in human and Atlantic cod larval cells. Intriguingly, we uncovered that all selected MHC class I variants localize to endolysosomal compartments in Atlantic cod cells. Additionally, by introducing point mutations or deletions in the cytosolic tail, we found that hypothetical sorting signals in the MHC class I cytosolic tail do not influence MHC class I trafficking. Moreover, we demonstrated that in Atlantic cod, tapasin and MHC class I colocalize on endolysosomes suggesting that peptide-loading assistance and stabilization of MHC class I occurs outside the endoplasmic reticulum. Altogether, our results demonstrate that MHC class I from Atlantic cod is sorted to the endolysosomal system, which may indicate that it interacts with exogenous peptides for potential cross presentation.

• Guslund, Naomi Croft; Krabberød, Anders Kristian; Nørstebø, Simen Foyn; Solbakken, Monica Hongrø; Jakobsen, Kjetill Sigurd & Johansen, Finn-Eirik [Show all 7 contributors for this article] (2022). Lymphocyte subsets in Atlantic cod (Gadus morhua) interrogated by single-cell sequencing. Communications Biology. 5:689(1), p. 1–9. doi: 10.1038/s42003-022-03645-w. Full text in Research Archive Show summary

  Abstract Atlantic Cod ( Gadus morhua ) has lost the major histocompatibility complex class II presentation pathway. We recently identified CD8-positive T cells, B cells, and plasma cells in cod, but further characterisation of lymphocyte subsets is needed to elucidate immune adaptations triggered by the absence of CD4-positive T lymphocytes. Here, we use single-cell RNA sequencing to examine the lymphocyte heterogeneity in Atlantic cod spleen. We describe five T cell subsets and eight B cell subsets and propose a B cell trajectory of differentiation. Notably, we identify a subpopulation of T cells that are CD8-negative. Most of the CD8-negative T lymphocytes highly express the homologue of monocyte chemotactic protein 1b , and another subset of CD8-negative T lymphocytes express the homologue of the scavenger receptor m130 . Uncovering the multiple lymphocyte cell sub-clusters reveals the different immune states present within the B and T cell populations, building a foundation for further work.

• Ghorbani, Atefeh; Khataeipour, S. Javad; Solbakken, Monica Hongrø; Huebert, David N. G.; Khoddami, Minasadat & Eslamloo, Khalil [Show all 11 contributors for this article] (2022). Ancestral reconstruction reveals catalytic inactivation of activation-induced cytidine deaminase concomitant with cold water adaption in the Gadiformes bony fish. BMC Biology. 20(293). doi: 10.1186/s12915-022-01489-8. Full text in Research Archive Show summary

  Background Antibody affinity maturation in vertebrates requires the enzyme activation-induced cytidine deaminase (AID) which initiates secondary antibody diversification by mutating the immunoglobulin loci. AID-driven antibody diversification is conserved across jawed vertebrates since bony and cartilaginous fish. Two exceptions have recently been reported, the Pipefish and Anglerfish, in which the AID-encoding aicda gene has been lost. Both cases are associated with unusual reproductive behavior, including male pregnancy and sexual parasitism. Several cold water fish in the Atlantic cod (Gadinae) family carry an aicda gene that encodes for a full-length enzyme but lack affinity-matured antibodies and rely on antibodies of broad antigenic specificity. Hence, we examined the functionality of their AID. Results By combining genomics, transcriptomics, immune responsiveness, and functional enzymology of AID from 36 extant species, we demonstrate that AID of that Atlantic cod and related fish have extremely lethargic or no catalytic activity. Through ancestral reconstruction and functional enzymology of 71 AID enzymes, we show that this enzymatic inactivation likely took place relatively recently at the emergence of the true cod family (Gadidae) from their ancestral Gadiformes order. We show that this AID inactivation is not only concordant with the previously shown loss of key adaptive immune genes and expansion of innate and cell-based immune genes in the Gadiformes but is further reflected in the genomes of these fish in the form of loss of AID-favored sequence motifs in their immunoglobulin variable region genes. Conclusions Recent demonstrations of the loss of the aicda gene in two fish species challenge the paradigm that AID-driven secondary antibody diversification is absolutely conserved in jawed vertebrates. These species have unusual reproductive behaviors forming an evolutionary pressure for a certain loss of immunity to avoid tissue rejection. We report here an instance of catalytic inactivation and functional loss of AID rather than gene loss in a conventionally reproducing vertebrate. Our data suggest that an expanded innate immunity, in addition to lower pathogenic pressures in a cold environment relieved the pressure to maintain robust secondary antibody diversification. We suggest that in this unique scenario, the AID-mediated collateral genome-wide damage would form an evolutionary pressure to lose AID function.

• Taugbøl, Annette; Solbakken, Monica Hongrø; Jakobsen, Kjetill Sigurd & Vøllestad, Leif Asbjørn (2022). Salinity-induced transcriptome profiles in marine and freshwater threespine stickleback after an abrupt 6-hour exposure. Ecology and Evolution. 12(10). doi: 10.1002/ece3.9395. Full text in Research Archive Show summary

  Saltwater and freshwater environments have opposing physiological challenges, yet, there are fish species that are able to enter both habitats during short time spans, and as individuals they must therefore adjust quickly to osmoregulatory contrasts. In this study, we conducted an experiment to test for plastic responses to abrupt salinity changes in two populations of threespine stickleback, Gasterosteus aculeatus, representing two ecotypes (freshwater and ancestral saltwater). We exposed both ecotypes to abrupt native (control treatment) and non- native salinities (0‰ and 30‰) and sampled gill tissue for transcriptomic analyses after 6 h of exposure. To investi-gate genomic responses to salinity, we analyzed four different comparisons; one for each ecotype (in their control and exposure salinity; (1) and (2), one between ecotypes in their control salinity (3), and the fourth comparison included all transcripts identi-fied in (3) that did not show any expressional changes within ecotype in either the control or the exposed salinity (4)). Abrupt salinity transfer affected the expression of 10 and 1530 transcripts for the saltwater and freshwater ecotype, respectively, and 1314 were differentially expressed between the controls, including 502 that were not affected by salinity within ecotype (fixed expression). In total, these results indicate that factors other than genomic expressional plasticity are important for osmoregula-tion in stickleback, due to the need for opposite physiological pathways to survive the abrupt change in salinity. functional genomics, gene expression, osmoregulation, phenotypic plasticity, salinity tolerance, Genetics

• Nilsson, Pernille; Solbakken, Monica Hongrø; Schmid, Boris Valentijn; Orr, Russell; Lv, Ruichen & Cui, Yujun [Show all 15 contributors for this article] (2020). The Genome of the Great Gerbil Reveals Species-Specific Duplication of an MHCII Gene. Genome Biology and Evolution (GBE). 12(2), p. 3832–3849. doi: 10.1093/gbe/evaa008. Full text in Research Archive Show summary

  Abstract The great gerbil (Rhombomys opimus) is a social rodent living in permanent, complex burrow systems distributed throughout Central Asia, where it serves as the main host of several important vector-borne infectious pathogens including the well-known plague bacterium (Yersinia pestis). Here, we present a continuous annotated genome assembly of the great gerbil, covering over 96% of the estimated 2.47-Gb genome. Taking advantage of the recent genome assemblies of the sand rat (Psammomys obesus) and the Mongolian gerbil (Meriones unguiculatus), comparative immunogenomic analyses reveal shared gene losses within TLR gene families (i.e., TLR8, TLR10, and the entire TLR11-subfamily) for Gerbillinae, accompanied with signs of diversifying selection of TLR7 and TLR9. Most notably, we find a great gerbil-specific duplication of the MHCII DRB locus. In silico analyses suggest that the duplicated gene provides high peptide binding affinity for Yersiniae epitopes as well as Leishmania and Leptospira epitopes, putatively leading to increased capability to withstand infections by these pathogens. Our study demonstrates the power of whole-genome sequencing combined with comparative genomic analyses to gain deeper insight into the immunogenomic landscape of the great gerbil and its close relatives.

• Jin, Xingkun; Morro, Bernat; Tørresen, Ole K.; Moiche, Visila; Solbakken, Monica Hongrø & Jakobsen, Kjetill Sigurd [Show all 8 contributors for this article] (2020). Innovation in Nucleotide-Binding Oligomerization-Like Receptor and Toll-Like Receptor Sensing Drives the Major Histocompatibility Complex-II Free Atlantic Cod Immune System. Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.609456. Full text in Research Archive
• Croft, Naomi; Solbakken, Monica Hongrø; Brieuc, Marine Servane Ono; Jentoft, Sissel; Jakobsen, Kjetill Sigurd & Qiao, Shuo Wang (2020). Single-Cell Transcriptome Profiling of Immune Cell Repertoire of the Atlantic Cod Which Naturally Lacks the Major Histocompatibility Class II System. Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.559555. Full text in Research Archive
• Adrian-Kalchhauser, Irene; Blomberg, Anders; Larsson, Tomas; Musilova, Zuzana; Peart, Claire R. & Pippel, Martin [Show all 18 contributors for this article] (2020). The round goby genome provides insights into mechanisms that may facilitate biological invasions. BMC Biology. 18(11), p. 1–33. doi: 10.1186/s12915-019-0731-8. Full text in Research Archive Show summary

  Background The invasive benthic round goby (Neogobius melanostomus) is the most successful temperate invasive fish and has spread in aquatic ecosystems on both sides of the Atlantic. Invasive species constitute powerful in situ experimental systems to study fast adaptation and directional selection on short ecological timescales and present promising case studies to understand factors involved the impressive ability of some species to colonize novel environments. We seize the unique opportunity presented by the round goby invasion to study genomic substrates potentially involved in colonization success. Results We report a highly contiguous long-read-based genome and analyze gene families that we hypothesize to relate to the ability of these fish to deal with novel environments. The analyses provide novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns of epigenetic regulators, and the presence of osmoregulatory genes that may have contributed to the round goby’s capacity to invade cold and salty waters. A recurring theme across all analyzed gene families is gene expansions. Conclusions The expanded innate immune system of round goby may potentially contribute to its ability to colonize novel areas. Since other gene families also feature copy number expansions in the round goby, and since other Gobiidae also feature fascinating environmental adaptations and are excellent colonizers, further long-read genome approaches across the goby family may reveal whether gene copy number expansions are more generally related to the ability to conquer new habitats in Gobiidae or in fish.

• Roth, Olivia; Solbakken, Monica Hongrø; Tørresen, Ole K.; Bayer, Till; Matschiner, Michael & Baalsrud, Helle Tessand [Show all 12 contributors for this article] (2020). Evolution of male pregnancy associated with remodeling of canonical vertebrate immunity in seahorses and pipefishes. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 117(17), p. 9431–9439. doi: 10.1073/pnas.1916251117. Full text in Research Archive Show summary

  A fundamental problem for the evolution of pregnancy, the most specialized form of parental investment among vertebrates, is the rejection of the nonself-embryo. Mammals achieve immunological tolerance by down-regulating both major histocompatibility complex pathways (MHC I and II). Although pregnancy has evolved multiple times independently among vertebrates, knowledge of associated immune system adjustments is restricted to mammals. All of them (except monotremata) display full internal pregnancy, making evolutionary reconstructions within the class mammalia meaningless. Here, we study the seahorse and pipefish family (syngnathids) that have evolved male pregnancy across a gradient from external oviparity to internal gestation. We assess how immunological tolerance is achieved by reconstruction of the immune gene repertoire in a comprehensive sample of 12 seahorse and pipefish genomes along the “male pregnancy” gradient together with expression patterns of key immune and pregnancy genes in reproductive tissues. We found that the evolution of pregnancy coincided with a modification of the adaptive immune system. Divergent genomic rearrangements of the MHC II pathway among fully pregnant species were identified in both genera of the syngnathids: The pipefishes (Syngnathus) displayed loss of several genes of the MHC II pathway while seahorses (Hippocampus) featured a highly divergent invariant chain (CD74). Our findings suggest that a trade-off between immunological tolerance and embryo rejection accompanied the evolution of unique male pregnancy. That pipefishes survive in an ocean of microbes without one arm of the adaptive immune defense suggests a high degree of immunological flexibility among vertebrates, which may advance our understanding of immune-deficiency diseases.

• Solbakken, Monica Hongrø; Jentoft, Sissel; Reitan, Trond; Mikkelsen, Helene; Jakobsen, Kjetill Sigurd & Seppola, Marit (2019). Whole transcriptome analysis of the Atlantic cod vaccine response reveals subtle changes in adaptive immunity. Comparative Biochemistry and Physiology - Part D:Genomics and Proteomics. ISSN 1744-117X. 31:100597, p. 1–12. doi: 10.1016/j.cbd.2019.100597. Full text in Research Archive Show summary

  Atlantic cod has lost the Major Histocompatibility complex class II pathway – central to pathogen presentation, humoral response and immunity. Here, we investigate the immunological response of Atlantic cod subsequent to dip vaccination with <i>Vibrio anguillarum</i> bacterin using transcriptome sequencing. The experiment was conducted on siblings from an Atlantic cod family found to be highly susceptible towards vibriosis where vaccination has demonstrated improved pathogen resistance. Gene expression analyses at 2, 4, 21 and 42 days post vaccination revealed GO-term enrichment for muscle, neuron and metabolism-related pathways. In-depth characterization of immune-related GO terms demonstrated down-regulation of MHCI antigen presentation, C-type lectin receptor signaling and granulocyte activation over time. Phagocytosis, interferon-gamma signaling and negative regulation of innate immunity were increasingly up-regulated over time. Individual differentially expressed immune genes implies weak initiation of acute phase proteins with little or no inflammation. Furthermore, gene expression indicates presence of T-cells, NK-like cells, B-cells and monocytes/macrophages. Three <i>MHCI</i> transcripts were up-regulated with <i>B2M</i> and <i>SEC61</i>. Overall, we find no clear immune-related transcriptomic response which could be attributed to Atlantic cod's alternative immune system. However, we cannot rule out that this response is related to vaccination protocol/sampling strategy. Earlier functional studies demonstrate significant memory in Atlantic cod post dip vaccination and combined with our results indicate the presence of other adaptive immunity mechanisms. In particular, we suggest that further investigations should look into CD8+ memory T-cells, γδ T-cells, T-cell independent memory or memory induced through NK-like/other lymphoid cells locally in the mucosal lining for this particular vaccination strategy.

• Inkpen, Sabrina; Solbakken, Monica Hongrø; Jentoft, Sissel; Eslamloo, Khalil & Rise, Matthew L. (2019). Full characterization and transcript expression profiling of the interferon regulatory factor (IRF) gene family in Atlantic cod (Gadus morhua). Developmental and Comparative Immunology. ISSN 0145-305X. 98, p. 166–180. doi: 10.1016/j.dci.2019.03.015. Full text in Research Archive Show summary

  Atlantic cod (Gadus morhua) represents a unique immune system among teleost fish, making it a species of interest for immunological studies, and especially for investigating the evolutionary history of immune gene families. The interferon regulatory factor (IRF) gene family encodes transcription factors which function in the interferon pathway, but also in areas including leukocyte differentiation, cell growth, autoimmunity, and development. We previously characterized several IRF family members in Atlantic cod (Irf4a, Irf4b, Irf7, Irf8, and two Irf10 splice variants) at the cDNA and putative amino acid levels, and in the current study we took advantage of the new and improved Atlantic cod genome assembly in combination with rapid amplification of cDNA ends (RACE) to characterize the remaining family members (i.e. Irf3, Irf5, Irf6, Irf9, and two Irf2 splice variants). Real-time quantitative PCR (QPCR) was used to investigate constitutive expression of all IRF transcripts during embryonic development, suggesting several putative maternal transcripts, and potential stage-specific roles. QPCR studies also showed 11 of 13 transcripts were responsive to stimulation with poly(I:C), while 6 of 13 transcripts were responsive to lipopolysaccharide (LPS) in Atlantic cod head kidney macrophages, indicating roles for cod IRF family members in both antiviral and antibacterial responses. This study is the first to investigate expression of the complete IRF family in Atlantic cod, and suggests potential novel roles for several of these transcription factors within immunity as well as in early development of this species.

• Solbakken, Monica Hongrø; Jentoft, Sissel; Reitan, Trond; Mikkelsen, Helene; Gregers, Tone Fredsvik & Bakke, Oddmund [Show all 8 contributors for this article] (2019). Disentangling the immune response and host-pathogen interactions in Francisella noatunensis infected Atlantic cod. Comparative Biochemistry and Physiology - Part D:Genomics and Proteomics. ISSN 1744-117X. 30, p. 333–346. doi: 10.1016/j.cbd.2019.04.004. Full text in Research Archive Show summary

  The genetic repertoire underlying teleost immunity has been shown to be highly variable. A rare example is Atlantic cod and its relatives Gadiformes that lacks a hallmark of vertebrate immunity: Major Histocompatibility Complex class II. No immunological studies so far have fully unraveled the functionality of this particular immune system. Through global transcriptomic profiling, we investigate the immune response and host-pathogen interaction of Atlantic cod infected with the facultative intracellular bacterium <i>Francisella noatunensis</i>. We find that Atlantic cod displays an overall classic innate immune response with inflammation, acute-phase proteins and cell recruitment through up-regulation of e.g. <i>IL1B</i>, fibrinogen, cathelicidin, hepcidin and several chemotactic cytokines such as the neutrophil attractants <i>CXCL1</i> and <i>CXCL8</i>. In terms of adaptive immunity, we observe up-regulation of interferon gamma followed by up-regulation of several <i>MHCI</i> transcripts and genes related to antigen transport and loading. Finally, we find up-regulation of immunoglobulins and down-regulation of T-cell and NK-like cell markers. Our analyses also uncover some contradictory transcriptional findings such as up-regulation of anti-inflammatory <i>IL10</i> as well as down-regulation of the NADPH oxidase complex and myeloperoxidase. This we interpret as the result of host-pathogen interactions where <i>F. noatunensis</i> modulates the immune response. In summary, our results suggest that Atlantic cod mounts a classic innate immune response as well as a neutrophil-driven response. In terms of adaptive immunity, both endogenous and exogenous antigens are being presented on MHCI and antibody production is likely enabled through direct B-cell stimulation with possible neutrophil help. Collectively, we have obtained novel insight in the orchestration of the Atlantic cod immune system and determined likely targets of <i>F. noatunensis</i> host-pathogen interactions.

• Skrede, Inger; Solbakken, Monica Hongrø; Hess, Jaqueline; Fossdal, Carl Gunnar; Hegnar, Olav Aaseth & Alfredsen, Gry (2019). Wood Modification by Furfuryl Alcohol Resulted in a Delayed Decomposition Response in Rhodonia (Postia) placenta. Applied and Environmental Microbiology. ISSN 0099-2240. 85(14), p. 1–21. doi: 10.1128/AEM.00338-19. Full text in Research Archive Show summary

  The aim of this study was to investigate differential expression profiles of the brown rot fungus Rhodonia placenta (previously Postia placenta) harvested at several time points when grown on radiata pine (Pinus radiata) and radiata pine with three different levels of modification by furfuryl alcohol, an environmentally benign commercial wood protection system. The entire gene expression pattern of a decay fungus was followed in untreated and modified wood from initial to advanced stages of decay. The results support the current model of a two-step decay mechanism, with the expression of genes related to initial oxidative depolymerization, followed by an accumulation of transcripts of genes related to the hydrolysis of cell wall polysaccharides. When the wood decay process is finished, the fungus goes into starvation mode after five weeks when grown on unmodified radiata pine wood. The pattern of repression of oxidative processes and oxalic acid synthesis found in radiata pine at later stages of decay is not mirrored for the high-furfurylation treatment. The high treatment level provided a more unpredictable expression pattern throughout the incubation period. Furfurylation does not seem to directly influence the expression of core plant cell wall-hydrolyzing enzymes, as a delayed and prolonged, but similar, pattern was observed in the radiata pine and the modified experiments. This indicates that the fungus starts a common decay process in the modified wood but proceeds at a slower pace as access to the plant cell wall polysaccharides is restricted. This is further supported by the downregulation of hydrolytic enzymes for the high treatment level at the last harvest point (mass loss, 14%). Moreover, the mass loss does not increase during the last weeks. Collectively, this indicates a potential threshold for lower mass loss for the high-furfurylation treatment. IMPORTANCE Fungi are important decomposers of woody biomass in natural habitats. Investigation of the mechanisms employed by decay fungi in their attempt to degrade wood is important for both the basic scientific understanding of ecology and carbon cycling in nature and for applied uses of woody materials. For wooden building materials, long service life and carbon storage are essential, but decay fungi are responsible for massive losses of wood in service. Thus, the optimization of durable wood products for the future is of major importance. In this study, we have investigated the fungal genetic response to furfurylated wood, a commercial environmentally benign wood modification approach that improves the service life of wood in outdoor applications. Our results show that there is a delayed wood decay by the fungus as a response to furfurylated wood, and new knowledge about the mechanisms behind the delay is provided.

• Lie, Kai Kristoffer; Tørresen, Ole K.; Solbakken, Monica Hongrø; Rønnestad, Ivar; Tooming-Klunderud, Ave & Nederbragt, Alexander Johan [Show all 8 contributors for this article] (2018). Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish. BMC Genomics. 19(186), p. 1–17. doi: 10.1186/s12864-018-4570-8. Full text in Research Archive Show summary

  Background: The ballan wrasse (Labrus bergylta) belongs to a large teleost family containing more than 600 species showing several unique evolutionary traits such as lack of stomach and hermaphroditism. Agastric fish are found throughout the teleost phylogeny, in quite diverse and unrelated lineages, indicating stomach loss has occurred independently multiple times in the course of evolution. By assembling the ballan wrasse genome and transcriptome we aimed to determine the genetic basis for its digestive system function and appetite regulation. Among other, this knowledge will aid the formulation of aquaculture diets that meet the nutritional needs of agastric species. Results: Long and short read sequencing technologies were combined to generate a ballan wrasse genome of 805 Mbp. Analysis of the genome and transcriptome assemblies confirmed the absence of genes that code for proteins involved in gastric function. The gene coding for the appetite stimulating protein ghrelin was also absent in wrasse. Gene synteny mapping identified several appetite-controlling genes and their paralogs previously undescribed in fish. Transcriptome profiling along the length of the intestine found a declining expression gradient from the anterior to the posterior, and a distinct expression profile in the hind gut. Conclusions: We showed gene loss has occurred for all known genes related to stomach function in the ballan wrasse, while the remaining functions of the digestive tract appear intact. The results also show appetite control in ballan wrasse has undergone substantial changes. The loss of ghrelin suggests that other genes, such as motilin, may play a ghrelin like role. The wrasse genome offers novel insight in to the evolutionary traits of this large family. As the stomach plays a major role in protein digestion, the lack of genes related to stomach digestion in wrasse suggests it requires formulated diets with higher levels of readily digestible protein than those for gastric species.

• Tørresen, Ole K.; Brieuc, Marine Servane; Solbakken, Monica Hongrø; Sørhus, Elin; Nederbragt, Alexander Johan & Jakobsen, Kjetill Sigurd [Show all 9 contributors for this article] (2018). Genomic architecture of haddock (Melanogrammus aeglefinus) shows expansions of innate immune genes and short tandem repeats. BMC Genomics. 19(240), p. 1–17. doi: 10.1186/s12864-018-4616-y. Full text in Research Archive Show summary

  Increased availability of genome assemblies for non-model organisms has resulted in invaluable biological and genomic insight into numerous vertebrates, including teleosts. Sequencing of the Atlantic cod (Gadus morhua) genome and the genomes of many of its relatives (Gadiformes) demonstrated a shared loss of the major histocompatibility complex (MHC) II genes 100 million years ago. An improved version of the Atlantic cod genome assembly shows an extreme density of tandem repeats compared to other vertebrate genome assemblies. Highly contiguous assemblies are therefore needed to further investigate the unusual immune system of the Gadiformes, and whether the high density of tandem repeats found in Atlantic cod is a shared trait in this group.

• Solbakken, Monica Hongrø; Voje, Kjetil L.; Jakobsen, Kjetill Sigurd & Jentoft, Sissel (2017). Linking species habitat and past palaeoclimatic events to evolution of the teleost innate immune system. Proceedings of the Royal Society of London. Biological Sciences. ISSN 0962-8452. 284(1853), p. 1–9. doi: 10.1098/rspb.2016.2810. Full text in Research Archive Show summary

  Host-intrinsic factors as well as environmental changes are known to be strong evolutionary drivers defining the genetic foundation of immunity. Using a novel set of teleost genomes and a time-calibrated phylogeny, we here investigate the family of Toll-like receptor (TLR) genes and address the underlying evolutionary processes shaping the diversity of the first-line defence. Our findings reveal remarkable flexibility within the evolutionary design of teleost innate immunity characterized by prominent TLR gene losses and expansions. In the order of Gadiformes, expansions correlate with the loss of major histocompatibility complex class II (MHCII) and diversifying selection analyses support that this has fostered new immunological innovations in TLRs within this lineage. In teleosts overall, TLRs expansions correlate with species latitudinal distributions and maximum depth. By contrast, lineage-specific gene losses overlap with well-described changes in palaeoclimate (global ocean anoxia) and past Atlantic Ocean geography. In conclusion, we suggest that the evolvability of the teleost immune system has most likely played a prominent role in the survival and successful radiation of this lineage.

• Baalsrud, Helle Tessand; Voje, Kjetil L.; Tørresen, Ole Kristian; Solbakken, Monica Hongrø; Matschiner, Michael & Malmstrøm, Martin [Show all 10 contributors for this article] (2017). Evolution of Hemoglobin Genes in Codfishes Influenced by Ocean Depth. Scientific Reports. 7, p. 1–10. doi: 10.1038/s41598-017-08286-2. Full text in Research Archive Show summary

  Understanding the genetic basis of adaptation is one of the main enigmas of evolutionary biology. Among vertebrates, hemoglobin has been well documented as a key trait for adaptation to different environments. Here, we investigate the role of hemoglobins in adaptation to ocean depth in the diverse teleost order Gadiformes, with species distributed at a wide range of depths varying in temperature, hydrostatic pressure and oxygen levels. Using genomic data we characterized the full hemoglobin (Hb) gene repertoire for subset of species within this lineage. We discovered a correlation between expanded numbers of Hb genes and ocean depth, with the highest numbers in species occupying shallower, epipelagic regions. Moreover, we demonstrate that the Hb genes have functionally diverged through diversifying selection. Our results suggest that the more variable environment in shallower water has led to selection for a larger Hb gene repertoire and that Hbs have a key role in adaptive processes in marine environments.

• Baalsrud, Helle Tessand; Tørresen, Ole Kristian; Solbakken, Monica Hongrø; Salzburger, Walter; Hanel, Reinhold & Jakobsen, Kjetill Sigurd [Show all 7 contributors for this article] (2017). De Novo Gene Evolution of Antifreeze Glycoproteins in Codfishes Revealed by Whole Genome Sequence Data. Molecular Biology and Evolution (MBE). ISSN 0737-4038. 35(3), p. 593–606. doi: 10.1093/molbev/msx311. Full text in Research Archive Show summary

  New genes can arise through duplication of a pre-existing gene or de novo from non-coding DNA, providing raw material for evolution of new functions in response to a changing environment. A prime example is the independent evolution of antifreeze glycoprotein genes (afgps) in the Arctic codfishes and Antarctic notothenioids to prevent freezing. However, the highly repetitive nature of these genes complicates studies of their organization. In notothenioids, afgps evolved from an extant gene, yet the evolutionary origin of afgps in codfishes is unknown. Here, we demonstrate that afgps in codfishes have evolved de novo from non-coding DNA 13–18 Ma, coinciding with the cooling of the Northern Hemisphere. Using whole-genome sequence data from several codfishes and notothenioids, we find higher copy number of afgp in species exposed to more severe freezing suggesting a gene dosage effect. Notably, antifreeze function is lost in one lineage of codfishes analogous to the afgp losses in non-Antarctic notothenioids. This indicates that selection can eliminate the antifreeze function when freezing is no longer imminent. In addition, we show that evolution of afgp-assisting antifreeze potentiating protein genes (afpps) in notothenioids coincides with origin and lineage-specific losses of afgp. The origin of afgps in codfishes is one of the first examples of an essential gene born from non-coding DNA in a non-model species. Our study underlines the power of comparative genomics to uncover past molecular signatures of genome evolution, and further highlights the impact of de novo gene origin in response to a changing selection regime.

• Solbakken, Monica Hongrø; Rise, Matthew L.; Jakobsen, Kjetill Sigurd & Jentoft, Sissel (2016). Successive losses of central immune genes characterize the Gadiformes’ alternate immunity. Genome Biology and Evolution (GBE). 8(11), p. 3508–3515. doi: 10.1093/gbe/evw250. Full text in Research Archive Show summary

  Great genetic variability among teleost immunomes, with gene losses and expansions of central adaptive and innate components, has been discovered through genome sequencing over the last few years. Here, we demonstrate that the innate Myxovirus resistance gene (Mx) is lost from the ancestor of Gadiformes and the closely related Stylephorus chordatus, thus predating the loss of Major Histocompatibility Complex class II (MHCII) in Gadiformes. Although the functional implication of Mx loss is still unknown, we demonstrate that this loss is one of several ancient events appearing in successive order throughout the evolution of teleost immunity. In particular, we find that the loss of Toll-like receptor 5 predates the loss of Mx involving the entire Paracanthopterygii lineage. Using a time-calibrated phylogeny, we show that loss of MHCII and Mx overlap with major paleoclimatic and geological events indicating thatthese genetic changes were adaptive responses to the changing environment at the time.

• Solbakken, Monica Hongrø; Tørresen, Ole Kristian; Nederbragt, Alexander Johan; Seppola, Marit; Gregers, Tone Fredsvik & Jakobsen, Kjetill Sigurd [Show all 7 contributors for this article] (2016). Evolutionary redesign of the Atlantic cod (Gadus morhua L.) Toll-like receptor repertoire by gene losses and expansions. Scientific Reports. 6. doi: 10.1038/srep25211. Full text in Research Archive Show summary

  Genome sequencing of the teleost Atlantic cod demonstrated loss of the Major Histocompatibility Complex (MHC) class II, an extreme gene expansion of MHC class I and gene expansions and losses in the innate pattern recognition receptor (PRR) family of Toll-like receptors (TLR). In a comparative genomic setting, using an improved version of the genome, we characterize PRRs in Atlantic cod with emphasis on TLRs demonstrating the loss of TLR1/6, TLR2 and TLR5 and expansion of TLR7, TLR8, TLR9, TLR22 and TLR25. We find that Atlantic cod TLR expansions are strongly influenced by diversifying selection likely to increase the detectable ligand repertoire through neo- and subfunctionalization. Using RNAseq we find that Atlantic cod TLRs display likely tissue or developmental stage-specific expression patterns. In a broader perspective, a comprehensive vertebrate TLR phylogeny reveals that the Atlantic cod TLR repertoire is extreme with regards to losses and expansions compared to other teleosts. In addition we identify a substantial shift in TLR repertoires following the evolutionary transition from an aquatic vertebrate (fish) to a terrestrial (tetrapod) life style. Collectively, our findings provide new insight into the function and evolution of TLRs in Atlantic cod as well as the evolutionary history of vertebrate innate immunity.

• Aas, Finn Erik; Li, Xi; Edwards, James; Solbakken, Monica Hongrø; Deeudom, Manu & Vik, Åshild [Show all 9 contributors for this article] (2015). Cytochrome c-based domain modularity governs genus-level diversification of electron transfer to dissimilatory nitrite reduction. Environmental Microbiology. ISSN 1462-2912. 17(6), p. 2114–2132. doi: 10.1111/1462-2920.12661. Full text in Research Archive
• Star, Bastiaan; Nederbragt, Alexander Johan; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin & Gregers, Tone Fredsvik [Show all 42 contributors for this article] (2011). The genome sequence of Atlantic cod reveals a unique immune system. Nature. ISSN 0028-0836. 477(7363), p. 207–210. doi: 10.1038/nature10342. Full text in Research Archive Show summary

  Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions5. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.

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• Solbakken, Monica Hongrø (2017). Functional comparative immunology – Atlantic cod and beyond. Full text in Research Archive
• Inkpen, Sabrina; Eslamloo, Khalil; Solbakken, Monica Hongrø; Jentoft, Sissel; Andreassen, Rune & Rise, Matthew L. (2017). Characterization and Expression Studies of the Interferon Regulatory Factor Gene Family in Atlantic cod (Gadus morhua). Full text in Research Archive
• Solbakken, Monica Hongrø (2013). The Atlantic cod immune system. Full text in Research Archive
• Solbakken, Monica Hongrø (2013). Functional insight into the innate immunity of Atlantic cod. Full text in Research Archive
• Solbakken, Monica Hongrø; Malmstrøm, Martin; Tørresen, Ole Kristian; Jakobsen, Kjetill Sigurd & Jentoft, Sissel (2013). Atlantic cod displays an unusual TLR repertoire – a Gadidae-specific feature? Full text in Research Archive
• Solbakken, Monica Hongrø; Jentoft, Sissel; Seppola, Marit; Mikkelsen, Helene & Jakobsen, Kjetill Sigurd (2013). The immune system of Atlantic cod. Full text in Research Archive
• Solbakken, Monica Hongrø (2012). Life without MHC-II; a dive into the immune system of Atlantic cod. Full text in Research Archive
• Star, Bastiaan; Nederbragt, Alexander Johan; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin & Gregers, Tone Fredsvik [Show all 18 contributors for this article] (2011). The genome of Atlantic cod reveals a unique immune system. Full text in Research Archive
• Kristoffersen, Tove; Landvik, Nina Elisabeth; Solbakken, Monica Hongrø; Karlsen, Harald; Haugen, Aage & Zienolddiny, Shanbeh (2010). Lack of interaction between functional polymorphisms in the MDM2 gene and exposure to 17-beta estradiol in vitro. European Journal of Cancer. ISSN 0959-8049. 8(5), p. 223–223. Full text in Research Archive
• Grimholt, Unni; Nederbragt, Alexander Johan; Rounge, Trine Ballestad; Malmstrøm, Martin; Star, Bastiaan & Tooming-Klunderud, Ave [Show all 12 contributors for this article] (2009). The cod genome project. Full text in Research Archive
• Solbakken, Monica Hongrø (2016). Evolutionary and functional insight into the teleost immune system — lessons learned from Atlantic cod and other teleosts. Universitetet i Oslo. Full text in Research Archive Show summary

  Teleosts comprise a very diverse group of species where genome sequencing the last decade has revealed great variability regarding their genetic basis for immunity. With emphasis on the innate immune system, this thesis addresses evolutionary and functional aspects of teleost immunity using high-throughput sequencing and bioinformatics analysis tools. The losses and expansions of Toll-like receptors (TLR) and loss of Major Histocompatibility Complex class II (MHCII) were originally discovered in Atlantic cod. TLRs are a gene family of pattern recognition receptors central to the functionality of innate immunity. The first paper in this thesis describes the in-depth characterization of Atlantic cod TLRs. The TLR repertoire, extreme compared to other teleosts and vertebrates, indicated a correlation with MHCII loss. In addition there were signs of diversifying selection within the TLR gene expansions suggesting sub- and neofunctionalization of the duplicated genes. Recently, through the use of new genome resources from 66 teleost species and corresponding species phylogeny, the loss of MHCII from the entire Gadiformes order was established. Using these genomes and phylogeny, we established the correlation between MHCII loss and TLR expansion within the order of Gadiformes (cod-like fish species). Moreover, we established correlations between the TLR expansion, species maximum depth and species latitudinal distribution — likely proxies for environmental abiotic factors such as temperature. We also investigated another long sought after gene in Atlantic cod — the Myxovirus resistance gene (Mx) — a viral infection marker with unknown function and considered a part of the innate immune system. Adding the Mx related findings to the teleost phylogeny showed that the changes to the teleost immune system are of a successive nature. The timing of the phylogeny demonstrated that well-described large alterations in past environment such as oceanic oxygen levels, temperature and layout of tectonic plates overlapped with the changes to the teleost immune system — illustrating the combined effect of host-intrinsic, biotic and abiotic factors on the evolution of the teleost immune system.

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