{"entity": "researcher", "timestamp": "2026-07-14T04:15:38.411Z", "family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "affiliations": ["Department of Biology Lund University Lund Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3"}}, "publications": [{"entity": "publication", "iuid": "b87ff717143c4bf38090dc1906217558", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b87ff717143c4bf38090dc1906217558.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b87ff717143c4bf38090dc1906217558"}}, "title": "Divergent cis regulatory haplotypes at Tlr2 are associated with immune responsiveness", "authors": [{"family": "Nandakumar", "given": "Mridula", "initials": "M", "orcid": "0000-0003-4133-7200", "researcher": {"href": "https://publications.scilifelab.se/researcher/62b3ae7920a94445baa9c525a56c0973.json"}}, {"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "Nouri", "given": "Mehrnaz", "initials": "M", "orcid": "0000-0001-6188-9171", "researcher": {"href": "https://publications.scilifelab.se/researcher/7345bf18ffa64e7f8888a9c540879265.json"}}, {"family": "Valfridsson", "given": "Christine", "initials": "C", "orcid": "0009-0005-0759-0220", "researcher": {"href": "https://publications.scilifelab.se/researcher/7cef4c3c125c4f75ba9abd19046cfc97.json"}}, {"family": "Carlsson", "given": "Fredric", "initials": "F", "orcid": "0000-0003-0875-4395", "researcher": {"href": "https://publications.scilifelab.se/researcher/d970f49b801a41eaafe818b724c03cda.json"}}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal-article", "published": "2026-05-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "0737-4038", "volume": "43", "issue": "5", "issn-l": null}, "abstract": "Positive and balancing selection on pattern recognition receptors (PRRs) is widely thought to target ligand-binding domains and affect the specificity of recognition of different pathogens. Alternatively, positive/balancing selection on PRRs could affect general responsiveness by targeting for example signaling domains or cis-regulatory variation. Studies of a wild rodent (the bank vole, Clethrionomys glareolus) have shown that Tlr2-a lipoprotein-binding PRR-is highly polymorphic with divergent haplotypes and signatures of balancing selection and that Tlr2 genotype is associated with susceptibility to Borrelia afzelii infection in the wild. To investigate what aspect of TLR2 function has been under selection, we here perform integrated population genetic and functional analyses. Ex vivo infection experiments show that the protective Tlr2 haplotype produces a stronger proinflammatory response to B. afzelii compared to the haplotype associated with susceptibility. Tlr2 genotype has a similar, albeit not statistically significant, effect on responsiveness to the phylogenetically distant pathogen Streptococcus pyogenes. We find that the strongest signature of balancing selection is 4.6 kb upstream of the Tlr2 CDS, near a putative enhancer, and that Tlr2 exhibits allele-specific expression such that the protective haplotype is more expressed. Collectively, these results indicate that balancing selection has primarily acted on cis-regulatory variation affecting the general responsiveness via TLR2 signaling rather than on polymorphisms affecting TLR2 ligand-binding specificity.", "doi": "10.1093/molbev/msag113", "pmid": "42052896", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13202456"}, {"db": "pii", "key": "8664598"}], "notes": [], "created": "2026-05-11T11:52:59.250Z", "modified": "2026-06-29T07:42:32.470Z"}, {"entity": "publication", "iuid": "be2943c4178e4522a7aec07e5c5f5cc6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be2943c4178e4522a7aec07e5c5f5cc6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be2943c4178e4522a7aec07e5c5f5cc6"}}, "title": "Positive Selection on Mammalian Immune Genes-Effects of Gene Function and Selective Constraint.", "authors": [{"family": "Nandakumar", "given": "Mridula", "initials": "M", "orcid": "0000-0003-4133-7200", "researcher": {"href": "https://publications.scilifelab.se/researcher/62b3ae7920a94445baa9c525a56c0973.json"}}, {"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "Carlsson", "given": "Fredric", "initials": "F", "orcid": "0000-0003-0875-4395", "researcher": {"href": "https://publications.scilifelab.se/researcher/d970f49b801a41eaafe818b724c03cda.json"}}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal article", "published": "2025-01-06", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "42", "issue": "1", "issn-l": "0737-4038"}, "abstract": "Genome-wide analyses of various taxa have repeatedly shown that immune genes are important targets of positive selection. However, little is known about what factors determine which immune genes are under positive selection. To address this question, we here focus on the mammalian immune system and investigate the importance of gene function and other factors such as gene expression, protein-protein interactions, and overall selective constraint as determinants of positive selection. We compiled a list of >1,100 immune genes that were divided into six functional categories and analyzed using data from rodents. Genes encoding proteins that are in direct interactions with pathogens, such as pattern recognition receptors (PRRs), are often expected to be key targets of positive selection. We found that categories containing cytokines, cytokine receptors, and other cell surface proteins involved in, for example, cell-cell interactions were at least as important targets as PRRs, with three times higher rate of positive selection than nonimmune genes. The higher rate of positive selection on cytokines and cell surface proteins was partly an effect of these categories having lower selective constraint. Nonetheless, cytokines had a higher rate of positive selection than nonimmune genes even at a given level of selective constraint, indicating that gene function per se can also be a determinant of positive selection. These results have broad implications for understanding the causes of positive selection on immune genes, specifically the relative importance of host-pathogen coevolution versus other processes.", "doi": "10.1093/molbev/msaf016", "pmid": "39834162", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11783303"}, {"db": "pii", "key": "7965092"}], "notes": [], "created": "2025-11-21T09:29:18.915Z", "modified": "2025-11-21T09:29:19.178Z"}, {"entity": "publication", "iuid": "8cb53a7450cc4a7e80432a058a5d263d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8cb53a7450cc4a7e80432a058a5d263d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8cb53a7450cc4a7e80432a058a5d263d"}}, "title": "Comparison of spleen transcriptomes of two wild rodent species reveals differences in the immune response against Borrelia afzelii.", "authors": [{"family": "Zhong", "given": "Xiuqin", "initials": "X", "orcid": "0000-0002-4772-4255", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1847f16fd2a4d1cac925c7b89b70684.json"}}, {"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Ecol Evol", "issn": "2045-7758", "volume": "10", "issue": "13", "pages": "6421-6434", "issn-l": "2045-7758"}, "abstract": "Different host species often differ considerably in susceptibility to a given pathogen, but the causes of such differences are rarely known. The natural hosts of the tick-transmitted bacterium Borrelia afzelii, which is one of causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Previous studies have shown that B. afzelii-infected bank voles (Myodes glareolus) have about ten times higher bacterial load than infected yellow-necked mice (Apodemus flavicollis), indicating that these two species differ in resistance. In this study, we compared the immune response to B. afzelii infection in these host species by using RNA sequencing to quantify gene expression in spleen. Gene set enrichment analysis (GSEA) showed that several immune pathways were down-regulated in infected animals in both bank voles and yellow-necked mice. Moreover, IFN\u03b1 response was up-regulated in B. afzelii-infected yellow-necked mice, while IL6 signaling and the complement pathway were down-regulated in infected bank voles; differences in regulation of these three pathways between bank voles and yellow-necked mice could thus contribute to the difference in resistance to B. afzelii between the species. This study provides knowledge of gene expression induced by a zoonotic pathogen in its natural host, and possible species-specific regulation of immune responses associated with resistance.", "doi": "10.1002/ece3.6377", "pmid": "32724523", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ECE36377"}, {"db": "pmc", "key": "PMC7381583"}, {"db": "Dryad", "key": "10.5061/dryad.t1g1jwt02"}], "notes": [], "created": "2020-12-07T16:29:59.033Z", "modified": "2024-01-16T13:48:42.326Z"}, {"entity": "publication", "iuid": "3de081fdf4d54781aae6830f27ddb7e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3de081fdf4d54781aae6830f27ddb7e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3de081fdf4d54781aae6830f27ddb7e7"}}, "title": "Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent.", "authors": [{"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "Zhong", "given": "Xiuqin", "initials": "X", "orcid": "0000-0002-4772-4255", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1847f16fd2a4d1cac925c7b89b70684.json"}}, {"family": "Konrad", "given": "Anna", "initials": "A"}, {"family": "Olsen", "given": "Remi-Andr\u00e9", "initials": "RA"}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"volume": "29", "issn": "1365-294X", "issue": "11", "pages": "1990-2003", "title": "Mol. Ecol.", "issn-l": "0962-1083"}, "abstract": "Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.", "doi": "10.1111/mec.15459", "pmid": "32374503", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "Dryad", "key": "10.5061/dryad.2bvq83bms"}], "notes": [], "created": "2020-07-08T13:04:58.447Z", "modified": "2024-01-16T13:48:42.452Z"}]}