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This complex interaction has led to the development of a variety of defense mechanisms collectively termed as innate immunity. Innate immunity is the first line of defense against pathogens in most organisms. Despite the availability of genomic and protein data of insects, we do not understand how innate immunity has evolved. This study reports class-level analysis of innate immunity in\n                    <jats:italic toggle=\"yes\">Insecta<\/jats:italic>\n                    spanning approximately 300 million years ago of evolution. We used the available data on 27 insect species of five predominant orders to track the evolutionary paths of innate immune proteins. We analyzed orthogroups and gene family dynamics to identify core conserved components and lineage-specific innovations in immune genes. Through orthogroup analysis, we find an asymmetrical or incoherent distribution of orthologs within the immune orthogroups among the orders that present intriguing events such as gene duplications, losses and functional diversification. For example, instances of missing orthologs in corresponding immune orthogroups were noted for specific orders, such as Defensin in\n                    <jats:italic toggle=\"yes\">Lepidoptera<\/jats:italic>\n                    , transferrin in\n                    <jats:italic toggle=\"yes\">Hemiptera,<\/jats:italic>\n                    and Cathepsin B in\n                    <jats:italic toggle=\"yes\">Hymenoptera<\/jats:italic>\n                    . Lineage-specific conservation of antimicrobial peptides was observed in\n                    <jats:italic toggle=\"yes\">Lepidoptera<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Hymenoptera<\/jats:italic>\n                    . Interestingly, proteins like Peptidoglycan recognition protein (PGRP)-SA, Spatzle, and others have undergone major family expansion and contraction events in the insect species studied. By constructing phylogenies based on immune-related proteins and assessing the signatures of positive selection, we gained insights into diversification and adaptive evolution. Signatures of positive selection were only demonstrated by PGRP-SA and diptericin proteins, with a specific site under selection found in the latter. Our findings present a broad picture of how the five closely placed yet highly divergent orders of the class\n                    <jats:italic toggle=\"yes\">Insecta<\/jats:italic>\n                    have maintained innate immunity in close reference to their ecological niches. These findings can have practical implications in strategizing pest management and insect conservation in the wild.\n                  <\/jats:p>","DOI":"10.1177\/15578666261426005","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:42:20Z","timestamp":1774438940000},"page":"439-455","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cross-Order Comparative Genomics Analysis of Insect Innate Immunity Suggests Niche-Specific Adaptation"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6474-0974","authenticated-orcid":false,"given":"Triveni","family":"Shelke","sequence":"first","affiliation":[{"name":"Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanika","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Zoology, Delhi University, Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ishaan","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/insects15050356"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1594"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.96738"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki070"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.002"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1994.0153"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icp043"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.03.027"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evac029"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msj037"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/insects11020095"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb08368.x"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010611"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-020117-043110"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.11.2568"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006795"},{"key":"e_1_3_3_18_1","unstructured":"DrosEU. \u2013 European Drosophila population genomics consortium. 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