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Here, we present the first comprehensive comparative and phylogenomic study of this lineage, integrating nuclear and mitochondrial genomes from 10 species across the Holarctic and Indomalayan realms. Our dataset includes two novel genome assemblies (Mustela strigidorsa, M. sibirica) and an improved genome for M. nivalis, enabling robust cross-species analyses of genome size, chromosomal evolution, genetic diversity, and demographic history. We uncover striking inter- and intraspecific variation in genome-wide heterozygosity and genome size, with evidence of marked homozygosity in some Asian lineages (M. eversmanii, M. sibirica, M. strigidorsa) and remarkable genetic diversity in widespread species such as M. nivalis and M. erminea. Phylogenomic results support the previously suggested split of M. richardsonii from M. erminea, but we found no evidence for speciation within M. nivalis. Ancestral reconstruction of chromosomal rearrangements revealed key chromosomal fissions that shaped the Mustelinae radiation, including early events predating the divergence of modern Mustela species. The results confirmed the suggested ancestral karyotypes of Mustela (2n = 44) and Mustelinae (2n = 42). Finally, demographic reconstructions exposed species-specific responses to Quaternary climatic cycles, ranging from long-term resilience in M. nivalis to repeated population bottlenecks in M. putorius and M. sibirica. Collectively, our findings establish a genomic foundation for future evolutionary and conservation genomic research on this emblematic Mustelidae lineage.<\/jats:p>","DOI":"10.1093\/gbe\/evag014","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:58:56Z","timestamp":1769086736000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative Genomics and Phylogenomics of the Mustelinae Lineage (Mustelidae, Carnivora)"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1236-631X","authenticated-orcid":false,"given":"Azamat A","family":"Totikov","sequence":"first","affiliation":[{"name":"Laboratory of Diversity and Evolution of Genomes, Institute of Molecular and Cellular Biology SB RAS , Novosibirsk 630090 ,","place":["Russia"]},{"name":"Department of Natural Sciences, Novosibirsk State University , Novosibirsk 630090 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University , Khanty-Mansiysk 628011 ,","place":["Russia"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0409-1371","authenticated-orcid":false,"given":"Natalia A","family":"Serdyukova","sequence":"additional","affiliation":[{"name":"Laboratory of Diversity and Evolution of Genomes, Institute of Molecular and Cellular Biology SB RAS , Novosibirsk 630090 ,","place":["Russia"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-0864","authenticated-orcid":false,"given":"Aliya R","family":"Yakupova","sequence":"additional","affiliation":[{"name":"Division of Evolutionary Biology, Ludwig-Maximilians-Universit\u00e4t , Planegg 82152 ,","place":["Germany"]},{"name":"Microevolution and Biodiversity, Max Planck Institute for Biological Intelligence , Seewiesen 82319 ,","place":["Germany"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-3822","authenticated-orcid":false,"given":"David","family":"Mohr","sequence":"additional","affiliation":[{"name":"Genetic Resources Core Facility, Department of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21287 ,","place":["USA"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-0404","authenticated-orcid":false,"given":"Daniel W","family":"Foerster","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Zoo and Wildlife Research (IZW) , Berlin 10315 ,","place":["Germany"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5328-3652","authenticated-orcid":false,"given":"Jose Horacio","family":"Grau Jipoulou","sequence":"additional","affiliation":[{"name":"Smithsonian Conservation Biology Institute, Center for Species Survival , Washington, DC ,","place":["USA"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-4143","authenticated-orcid":false,"given":"Violetta R","family":"Beklemisheva","sequence":"additional","affiliation":[{"name":"Laboratory of Diversity and Evolution of Genomes, Institute of Molecular and Cellular Biology SB RAS , Novosibirsk 630090 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