The ConGen Global course "Recent Advances in Conservation Genetics" was established to educate and empower new generations of researchers and practitioners in genetic and genomic approaches to biodiversity conservation. Since its first offering in 1996, the course has evolved from a focus on sample collection, population diversity assessment, and molecular phylogeography using (polymerase chain reaction (PCR) and Sanger sequencing to a curriculum centered on next-generation sequencing, whole-genome assembly, demographic inference, and bioinformatic analyses. Originally hosted at venues near Washington, D.C., the course expanded internationally in 2011 and has since been held near biodiversity hotspots across the globe, incorporating local researchers, and drawing an increasingly diverse global audience from every part of the world. Each edition integrates region-specific conservation challenges with hands-on tutorials, case studies, and personal narratives from leading conservation geneticists. This combination of rigorous science, practical applications, and international participation has created a uniquely impactful and inclusive program. Here, we review the last decade of ConGen Global (2015 to 2025), highlighting its contributions to conservation genetics education, its role in standardizing and disseminating new genomic methods, and its influence on policy-relevant research agendas. Beyond training, the course has shaped the broader field of conservation genetics by accelerating the adoption of genomic tools, strengthening global research networks, and translating genetic insights into conservation practice. Drawing on nearly three decades of experience, ConGen Global continues to serve as a model for advancing conservation genetics education and for inspiring future training programs worldwide.

The contemporary genetic diversity of the cheetah (Acinonyx jubatus) has been the focus of several studies, which have revealed very low levels of variation. Different hypotheses have been proposed to explain this pattern of low diversity, and require additional scrutiny. Here, we used published microsatellite data and coalescence-based analytical methods to explore the historical demography of the largest free-ranging cheetah population, aiming to assess whether present-day diversity may have been impacted by a historical demographic decline. Our results support the hypothesis of a historical (and most likely gradual) demographic decline over the past ~10,000 years, leading to a present-day N e ranging from 700 to 1,600 individuals. This decline was likely induced by climate-driven vegetational shifts affecting habitat suitability and possibly also interspecies interactions with prey and competitors. These results help clarify the demographic history of cheetahs in southern Africa and its impact on the current genetic diversity of this population.

In the fall of 2003, a 2-yr-old tiger named Ming, weighing around 300 pounds, was discovered living in an apartment in Harlem, New York. Ming's rescue by NYPD was witnessed, recalled, and venerated by scores of neighbors. The tiger's history and ancestry stimulated considerable media interest, investigative sleuthing, and forensic genomic analyses. The Harlem tiger's subspecies makeup, his relationship to his putative sibling named Cheeky living in Homestead, Florida, and his genetic distinctiveness from wild tigers was assessed by whole-genome sequence (WGS) analyses of trace materials from plucked whiskers. Verified subspecies ancestry of Ming and Cheeky was determined by comparing their WGS to single-nucleotide polymorphism (SNP) annotation from WGS of 35 voucher (pure subspecies) tiger specimens from six living subspecies. Genome-wide structure analyses based on the full set of 3,422,109 SNPs and a subset of 6,724 and 110 ancestry-informative markers showed that Ming has an admixed genetic background from five subspecies: Indochinese tiger (Panthera tigris corbetti 35 ~ 40%), Bengal tiger (P. t. tigris 17 ~ 23%), Sumatran tiger (P. t. sumatrae 12 ~ 14%), Amur tiger (P. t. altaica ~ 10%), and Malayan tiger (P. t. jacksoni 1 ~ 10%). Cheeky is confirmed to be a full sibling to Ming and displayed an admixed genetic background with similar subspecies proportions as Ming's. The forensic assessment of the tigers' subspecies composition, kinship, and recent history of animal transaction provides an analytical pipeline and holds promise for supporting global tiger conservation efforts through standardized genomic analysis of tigers or tiger products with unknown origins.

Abstract There has been a drastic decline in the number of cheetahs in the past century. Illegal pet trade poses a critical threat to the survival of the species and demands more attention. Genetic analysis of 55 cheetahs confiscated in Somaliland shows 100% as Acinonyx jubatus soemmeringii, suggesting that illegal trade subjects A. j. soemmeringii to significant pressure. Continued decline of the estimated 260–590 mature individuals qualifies this subspecies as “endangered” versus currently “vulnerable,” under criterion C2a(i) of the International Union for Conservation of Nature Red List. A population decline of ≥80% over the next 10 years or 3 generations would even fulfill criterion A3 of “critically endangered.” We urge reclassification of A. j. soemmeringii, as endangered, and appeal to the cheetah community to investigate further uplisting to critically endangered to reflect the likely extinction risk exacerbated by the illegal trade.

HIV infection continues to be a major global public health issue. The population heterogeneity in susceptibility or resistance to HIV-1 and progression upon infection is attributable to, among other factors, host genetic variation. Therefore, identifying population-specific variation and genetic modifiers of HIV infectivity can catapult the invention of effective strategies against HIV-1 in African populations. Here, we investigated whole genome sequences of 390 unrelated HIV-positive and -negative individuals from Botswana. We report 27.7 million single nucleotide variations (SNVs) in the complete genomes of Botswana nationals, of which 2.8 million were missing in public databases. Our population structure analysis revealed a largely homogenous structure in the Botswana population. Admixture analysis showed elevated components shared between the Botswana population and the Niger-Congo (65.9%), Khoe-San (32.9%), and Europeans (1.1%) ancestries in the population of Botswana. Statistical significance of the mutational burden of deleterious and loss-of-function variants per gene against a null model was estimated. The most deleterious variants were enriched in five genes: ACTRT2 (the Actin Related Protein T2), HOXD12 (homeobox D12), ABCB5 (ATP binding cassette subfamily B member 5), ATP8B4 (ATPase phospholipid transporting 8B4) and ABCC12 (ATP Binding Cassette Subfamily C Member 12). These genes are enriched in the glycolysis and gluconeogenesis (p < 2.84e-6) pathways and therefore, may contribute to the emerging field of immunometabolism in which therapy against HIV-1 infection is being evaluated. Published transcriptomic evidence supports the role of the glycolysis/gluconeogenesis pathways in the regulation of susceptibility to HIV, and that cumulative effects of genetic modifiers in glycolysis/gluconeogenesis pathways may potentially have effects on the expression and clinical variability of HIV-1. Identified genes and pathways provide novel avenues for other interventions, with the potential for informing the design of new therapeutics.

The tiger (Panthera tigris) is a charismatic megafauna species that originated and diversified in Asia and probably experienced population contraction and expansion during the Pleistocene, resulting in low genetic diversity of modern tigers. However, little is known about patterns of genomic diversity in ancient populations. Here we generated whole-genome sequences from ancient or historical (100-10,000 yr old) specimens collected across mainland Asia, including a 10,600-yr-old Russian Far East specimen (RUSA21, 8× coverage) plus six ancient mitogenomes, 14 South China tigers (0.1-12×) and three Caspian tigers (4-8×). Admixture analysis showed that RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some of the 8,000-10,000-yr-old Russian Far East mitogenomes are basal to all tigers, one 2,000-yr-old specimen resembles present Amur tigers. Phylogenomic analyses suggested that the Caspian tiger probably dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modelling suggested that Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, admixture between divergent lineages of South China tigers took place in Eastern China, promoting the evolution of other northern subspecies. Altogether, our analysis of ancient genomes sheds light on the evolutionary history of tigers and supports the existence of nine modern subspecies.

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.

Pusa sibirica, the Baikal seal, is the only extant, exclusively freshwater, pinniped species. The pending issue is, how and when they reached their current habitat—the rift lake Baikal, more than three thousand kilometers away from the Arctic Ocean. To explore the demographic history and genetic diversity of this species, we generated a de novo chromosome-length assembly, and compared it with three closely related marine pinniped species. Multiple whole genome alignment of the four species compared with their karyotypes showed high conservation of chromosomal features, except for three large inversions on chromosome VI. We found the mean heterozygosity of the studied Baikal seal individuals was relatively low (0.61 SNPs/kbp), but comparable to other analyzed pinniped samples. Demographic reconstruction of seals revealed differing trajectories, yet remarkable variations in Ne occurred during approximately the same time periods. The Baikal seal showed a significantly more severe decline relative to other species. This could be due to the difference in environmental conditions encountered by the earlier populations of Baikal seals, as ice sheets changed during glacial–interglacial cycles. We connect this period to the time of migration to Lake Baikal, which occurred ~3–0.3 Mya, after which the population stabilized, indicating balanced habitat conditions.

We report the first chromosome-length genome assemblies for three species in the mammalian order Pholidota: the white-bellied, Chinese, and Sunda pangolins. Surprisingly, we observe extraordinary karyotypic plasticity within this order and, in female white-bellied pangolins, the largest number of chromosomes reported in a Laurasiatherian mammal: 2n = 114. We perform the first karyotype analysis of an African pangolin and report a Y-autosome fusion in white-bellied pangolins, resulting in 2n = 113 for males. We employ a novel strategy to confirm the fusion and identify the autosome involved by finding the pseudoautosomal region (PAR) in the female genome assembly and analyzing the 3D contact frequency between PAR sequences and the rest of the genome in male and female white-bellied pangolins. Analyses of genetic variability show that white-bellied pangolins have intermediate levels of genome-wide heterozygosity relative to Chinese and Sunda pangolins, consistent with two moderate declines of historical effective population size. Our results reveal a remarkable feature of pangolin genome biology and highlight the need for further studies of these unique and endangered mammals.

Criteria for species naming have been contentious since the time of Carl Linnaeus.With no clear’right or wrong’convention for species naming,biologists strive to simply convince their peers.This NSR compendium offers detailed guidance [1-6] that adds quantitative genomic inference to the cacophony.Certain taxonomic assemblages （e.g.mammals,fish,fungi,insects,terrestrial and marine invertebrates,plants,bacteria） are sufficiently distinctive that any generalization is fraught with natural exceptions.

Observing Evolution—Peppered Moths and the Discovery of Parallel Melanism. Bruce S. Grant, Baltimore: Johns Hopkins University Press, 2021. Biology students everywhere are familiar with the industrial melanism story, a straightforward and compelling example of natural selection. Industrial melanism traces the rise of the pigmentation polymorphism of the peppered moth, Biston betularia, whose populations near English cities rapidly changed from light to dark body color in concert with the increasing smog and pollution of the Industrial Revolution. The abrupt change of the moth’s color frequencies was persuasively documented by Bernard Kettlewell. His research led to a cogent paradigm (his “contrast/conflict” model), which inferred that heritable differences between pale and melanistic phenotypes were somehow recognized by the individual moths. Pale moths would light upon the white tree lichens, while the melanistic moths chose sooty darker tree trunks. Kettlewell suggested the ongoing natural selection that drove this behavior arose as a...

Documenting genome diversity is important for the local biomedical communities and instrumental in developing precision and personalized medicine. Currently, tens of thousands of whole-genome sequences from Europe are publicly available, but most of these represent populations of developed countries of Europe. The uneven distribution of the available data is further impaired by the lack of data sharing. Recent whole-genome studies in Eastern Europe, one in Ukraine and one in Russia, demonstrated that local genome diversity and population structure fromEastern Europe historically had not been fully represented. An unexpected wealth of genomic variation uncovered in these studies was not so much a consequence of high variation within their population, but rather due to the "pioneer advantage." We discovered more variants because we were the first to prospect in the Eastern European genome pool. This simple comparison underscores the importance of removing the remaining geographic genome deserts from the rest of the world map of the human genome diversity.

Wide interest in species conservation is young. To many it began early in 1903 when Teddy Roosevelt and John Muir set up a camp under the Grizzly Giant in the Mariposa Grove of California's Yosemite Valley. Over three days they decided to broaden the US National Park footprint across the USA. Conservationists were inspired in the coming decades by the writings of wildlife conservation pioneers-Osa Johnson (I Married Adventure), Karen Blixen (Out of Africa) and Rachel Carson (The Silent Spring). Countless crusaders developed a passion for preserving dwindling species in those early days, yet none of these conservation advocates mentioned the word genetics, let alone genomics. The genome sequencing projects that have followed on from these have brought in an enormous amount of data, including whole genome sequences for thousands of non-human species, both individual and population wide. This huge resource has revolutionized conservation genetics, bringing in ways to assess the health of at-risk populations, devise genetic-driven breeding strategies, and other means to attempt to preserve the over 1 million species (and growing) under threat today.

Background: Autologous CAR-T cell therapies have shown significant benefit in the treatment of patients (pts) with relapsed/refractory B cell NHL (r/r B-NHL). Autologous CAR-T cells may have inherent functional deficiencies or yield an inconsistent product and their manufacturing is lengthy and complex. CB-010 is an allogeneic, anti-CD19 CAR-T cell therapy derived from healthy donor T cells. Pts receiving CB-010 do not require leukapheresis or bridging therapy. A next-generation CRISPR technology (Cas9 chRDNAs) that significantly reduces off-target editing was used to generate 3 genome edits in the manufacture of CB-010: knockout (KO) of the TRAC gene to eliminate TCR expression to reduce the risk of GvHD; site-specific insertion of an anti-CD19 CAR into the TRAC locus; and KO of the gene encoding PD-1, designed to limit CAR-T cell exhaustion. Statistically significant preclinical survival benefit across B-NHL subtypes and longer-duration efficacy in vivo compared to similar CAR-T cells without a PD-1 KO support the clinical evaluation of CB-010. Aims: To report the preliminary safety, tolerability, and initial antitumor efficacy of CB-010. Methods: ANTLER is a multicenter, Phase 1 trial in pts with r/r B-NHL. A 3 + 3 dose escalation design followed by expansion at the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) is used. Primary objectives are to determine the RP2D and the safety and tolerability of CB-010. Additional objectives include preliminary antitumor activity, and PK. After serially receiving lymphodepletion therapy with cyclophosphamide (60mg/kg/day x 2 days) and fludarabine (25mg/m2/day x 5 days), pts receive a single dose infusion of CB-010. Results: As of the data-cut-off date of 23 Feb 2022, 6 pts with r/r B-NHL (DLBCL: 2, PMBCL: 1, FL: 2, MCL: 1) were treated with CB-010 at the initial dose level of 40 x106 CAR-T cells. Pts received a median of 3 prior therapies (range 2-8), and all had relapsed on their last therapy. As of the data cut-off, 5 of 6 pts completed the 28-day DLT period. One CRS (Grade 1) has been reported; this pt experienced concurrent CRS and Grade 3 ICANS, characterized as a DLT. The pt received tocilizumab and steroids and recovered from the DLT within 39 hours. There were no cases of GvHD. In addition, 3 of 6 pts developed Grade 3 or 4 AEs within the first 28 days: neutropenia (50%), thrombocytopenia (33%), anemia (16.7%), and hypogammaglobulinaemia (16.7%). Results are preliminary and unaudited. Five out of 6 pts had post baseline tumor assessments and achieved complete response (4) or partial response (1). With a median follow up of 4.5 months (range: 0.6-8.6 months), 4 pts have ongoing responses, 1 pt relapsed at the 6-month evaluation and 1 patient is in the DLT evaluation period. Image:Summary/Conclusion: CB-010, an allogeneic CD19-directed CAR-T cell therapy with a PD-1 KO, demonstrated promising preliminary safety and efficacy in pts with r/r B-NHL at the initial dose level. The study is ongoing, and additional safety and efficacy data will be provided at the meeting. The trial is registered on clinicaltrials.gov (NCT04637763).

The contrast between the tiger’s ( Panthera tigris ) 2-3 My age and extant tigers’ coalescence approximately 110,000 years ago suggests an ancient demographic bottleneck. Here we collected over 60 extinct specimens across mainland Asia and generated whole genome sequences from a 10,600-year-old Russian Far East (RFE) specimen (RUSA21, 8ξ coverage), 14 South China tigers (0.1-12ξ), three Caspian tigers (4-8ξ), plus 17 new mitogenomes. RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some 8,000-10,000-year-old RFE mitogenomes are basal to all tigers, one 2,000-year-old specimen resembles present Amur tigers. The Caspian tiger likely dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modeling suggested Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, Eastern China became a genetic melting pot to foster divergent lineages to merge into South China tigers and other subsequent northern subspecies to develop. Genomic information retrieved from ancient tigers hence sheds light on the species’ full evolutionary history leading to nine modern subspecies and resolves the natural history of surviving tigers.