{"entity": "researcher", "timestamp": "2026-10-05T20:41:19.550Z", "family": "Nandakumar", "given": "Mridula", "initials": "M", "orcid": "0000-0003-4133-7200", "affiliations": ["Department of Biology, Lund University, Lund 223 62, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/62b3ae7920a94445baa9c525a56c0973.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/62b3ae7920a94445baa9c525a56c0973"}}, "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"}]}