Low genomic diversity is generally indicative of small population size and is considered detrimental by decreasing long-term adaptability.1,2,3,4,5,6 Moreover, small population size may promote gene flow with congeners and outbreeding depression.7,8,9,10,11,12,13 Here, we examine the connection between habitat availability, effective population size (Ne), and extinction by generating a 40× nuclear genome from the extinct blue antelope (Hippotragus leucophaeus). Historically endemic to the relatively small Cape Floristic Region in southernmost Africa,14,15 populations were thought to have expanded and contracted across glacial-interglacial cycles, tracking suitable habitat.16,17,18 However, we found long-term low Ne, unaffected by glacial cycles, suggesting persistence with low genomic diversity for many millennia prior to extinction in ∼AD 1800. A lack of inbreeding, alongside high levels of genetic purging, suggests adaptation to this long-term low Ne and that human impacts during the colonial era (e.g., hunting and landscape transformation), rather than longer-term ecological processes, were central to its extinction. Phylogenomic analyses uncovered gene flow between roan (H. equinus) and blue antelope, as well as between roan and sable antelope (H. niger), approximately at the time of divergence of blue and sable antelope (∼1.9 Ma). Finally, we identified the LYST and ASIP genes as candidates for the eponymous bluish pelt color of the blue antelope. Our results revise numerous aspects of our understanding of the interplay between genomic diversity and evolutionary history and provide the resources for uncovering the genetic basis of this extinct species\' unique traits.

As one of the most abundant groups in marine fish families, Gobiidae fish are important fishery resources in China, and some are also invasive species in certain regions worldwide. However, the phylogenetic relationships of Gobiidae fish remain ambiguous, and the study of their invasion-related genes is still scarce. This study used high-throughput sequencing technology to conduct a whole-genome survey of five Gobiidae fish species: Acanthogobius flavimanus, Acanthogobius stigmothonus, Favonigobius gymnauchen, Ctenotrypauchen microcephalus, and Tridentiger barbatus. De novo assembly of five fish genomes was performed, and genomic traits were compared through K-mer analysis. Among the five Gobiidae fish genomes, F. gymnauchen had the largest genome size (1601.98 Mb) and the highest heterozygosity (1.56%) and repeat rates (59.83%). Phylogenetic studies showed that A. flavimanus was most closely linked to A. stigmothonus, while Apogonidae and Gobiidae were closely related families. PSMC analysis revealed that C. microcephalus experienced a notable population expansion than the other four fish species in the Early Holocene. By using the KOG, GO, and KEGG databases to annotate single-copy genes, the annotated genes of the five fish were mainly classified as \"signal transduction mechanisms\", \"cellular process\", \"cellular anatomical entity\", and \"translation\". Acanthogobius flavimanus, A. stigmothonus, and T. barbatus had more genes classified as \"response to stimulus\" and \"localization\", which may have played an important role in their invasive processes. Our study also provides valuable material about Gobiidae fish genomics and genetic evolution.

UNASSIGNED: Several studies suggest that Proteasome 26S Subunit, ATPase (PSMC) family genes are of great importance in tumor progression and spreading, but the study for systematic evaluation of the function of PSMC genes in hepatocellular carcinoma (HCC) is currently lacking.
UNASSIGNED: The functions of PSMC genes in HCC were analyzed using multiple online databases, including the TCGA database, GEO database, HPA database, cBioPortal database, DAVID, and KEGG pathway. Experiments were later conducted to verify PSMC expression.
UNASSIGNED: High levels of PSMC gene expression were detected in HCC tissues and PSMCs exhibited potentially powerful abilities in diagnosing HCC patients. All PSMC proteins are expressed to varying degrees in HCC tissues and high expression of the PSMC genes lead to poor prognosis in patients with HCC. Moreover, DNA methylation involves the regulation of the expression of PSMC2 and PSMC5 in HCC, and the levels of methylation of PSMC2 or PSMC5 correlate positively with patient overall survival in HCC patients. The copy number alteration and mutation of PSMC genes were observed and related to the expression of PSMCs in HCC. Functional enrichment analysis showed that many highly co-expressed genes of PSMCs had a potential role in tumor progression and metastasis, which merited further in-depth study. Functional network analysis also suggests that the primary biological function of PSMC genes is the regulation of protein homeostasis and energy metabolism in HCC. Moreover, the expression levels of PSMCs are related to immune cell infiltrates and immunomodulatory factors in HCC.
UNASSIGNED: Our study indicates that PSMC genes are the potential target for precision immunotherapy and novel prognostic biomarkers for HCC.

Studies of species that experience environmental heterogeneity across their distributions have become an important tool for understanding mechanisms of adaptation and predicting responses to climate change. We examine population structure, demographic history and environmentally associated genomic variation in Bombus vosnesenskii, a common bumble bee in the western USA, using whole genome resequencing of populations distributed across a broad range of latitudes and elevations. We find that B. vosnesenskii exhibits minimal population structure and weak isolation by distance, confirming results from previous studies using other molecular marker types. Similarly, demographic analyses with Sequentially Markovian Coalescent models suggest that minimal population structure may have persisted since the last interglacial period, with genomes from different parts of the species range showing similar historical effective population size trajectories and relatively small fluctuations through time. Redundancy analysis revealed a small amount of genomic variation explained by bioclimatic variables. Environmental association analysis with latent factor mixed modelling (LFMM2) identified few outlier loci that were sparsely distributed throughout the genome and although a few putative signatures of selective sweeps were identified, none encompassed particularly large numbers of loci. Some outlier loci were in genes with known regulatory relationships, suggesting the possibility of weak selection, although compared with other species examined with similar approaches, evidence for extensive local adaptation signatures in the genome was relatively weak. Overall, results indicate B. vosnesenskii is an example of a generalist with a high degree of flexibility in its environmental requirements that may ultimately benefit the species under periods of climate change.

Okamejei kenojei is an important economic species widely distributed in shallow coastal waters of the western North Pacific. In this study, the whole-genome survey analysis of O. kenojei was conducted to reveal its genomic characteristics. The genome size was estimated to be 2027.44 Mb, the repeat sequence content was 44.90%, and the heterozygous ratio was 1.04%. The mitochondrial genome excavated from the sequencing data was 16,974 bp, and it can form the closed circular molecule. The phylogenetic tree based on 13 protein-coding gene sequences supported the validity of Okamejei and assisted the conclusion that Raja porosa was the junior synonym of O. kenojei. Plenty of potential microsatellite loci were identified, and the distribution frequency was estimated to be approximately 236.3 SSRs per Mb. Among all motif types of microsatellites, the dinucleotide repeats were dominant (82.59%), followed by the trinucleotide repeats (8.05%), tetranucleotide repeats (5.80%), pentanucleotide repeats (2.83%), and hexanucleotide repeats (0.72%). The results of the present study could not only provide useful information for understanding the genome structure and functional characteristics of O. kenojei, but also lay the foundation for the subsequent mapping of the whole genome.

Understanding historical range shifts and population size variation provides an important context for interpreting contemporary genetic diversity. Methods to predict changes in species distributions and model changes in effective population size (N e) using whole genomes make it feasible to examine how temporal dynamics influence diversity across populations. We investigate N e variation and climate-associated range shifts to examine the origins of a previously observed latitudinal heterozygosity gradient in the bumble bee Bombus vancouverensis Cresson (Hymenoptera: Apidae: Bombus Latreille) in western North America. We analyze whole genomes from a latitude-elevation cline using sequentially Markovian coalescent models of N e through time to test whether relatively low diversity in southern high-elevation populations is a result of long-term differences in N e. We use Maxent models of the species range over the last 130,000 years to evaluate range shifts and stability. N e fluctuates with climate across populations, but more genetically diverse northern populations have maintained greater N e over the late Pleistocene and experienced larger expansions with climatically favorable time periods. Northern populations also experienced larger bottlenecks during the last glacial period, which matched the loss of range area near these sites; however, bottlenecks were not sufficient to erode diversity maintained during periods of large N e. A genome sampled from an island population indicated a severe postglacial bottleneck, indicating that large recent postglacial declines are detectable if they have occurred. Genetic diversity was not related to niche stability or glacial-period bottleneck size. Instead, spatial expansions and increased connectivity during favorable climates likely maintain diversity in the north while restriction to high elevations maintains relatively low diversity despite greater stability in southern regions. Results suggest genetic diversity gradients reflect long-term differences in N e dynamics and also emphasize the unique effects of isolation on insular habitats for bumble bees. Patterns are discussed in the context of conservation under climate change.

Background: Proteasome 26S subunit, ATPase gene (PSMC) family members play a critical role in regulating protein degradation and are essential for tumor development. However, little is known about the integrative function and prognostic significance of the PSMC gene family members in lung cancer. Methods: First, we assessed the expression and prognostic features of six PSMC family members in pan-cancer from The Cancer Genome Atlas (TCGA) dataset. Hence, by focusing on the relationship between PSMC genes and the prognostic, genomic, and tumor microenvironment features in lung adenocarcinoma (LUAD), a PSMC-based prognostic signature was established using consensus clustering and multiple machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO) Cox regression, CoxBoost, and survival random forest analysis in TCGA and GSE72094. We then validated it in three independent cohorts from GEO and estimated the correlation between risk score and clinical features: genomic features (alterations, tumor mutation burden, and copy number variants), immune profiles (immune score, TIDE score, tumor-infiltrated immune cells, and immune checkpoints), sensitivity to chemotherapy (GDSC, GSE42127, and GSE14814), and immunotherapy (IMvigor210, GSE63557, and immunophenoscore). Twenty-one patients with LUAD were included in our local cohort, and tumor samples were submitted for evaluation of risk gene and PD-L1 expression. Results: Nearly all six PSMC genes were overexpressed in pan-cancer tumor tissues; however, in LUAD alone, they were all significantly correlated with overall survival. Notably, they all shared a positive association with increased TMB, TIDE score, expression of immune checkpoints (CD276 and PVR), and more M1 macrophages but decreased B-cell abundance. A PSMC-based prognostic signature was established based on five hub genes derived from the differential expression clusters of PSMC genes, and it was used to dichotomize LUAD patients into high- and low-risk groups according to the median risk score. The area under the curve (AUC) values for predicting survival at 1, 3, and 5 years in the training cohorts were all >.71, and the predictive accuracy was also robust and stable in the GSE72094, GSE31210, and GSE13213 datasets. The risk score was significantly correlated with advanced tumor, lymph node, and neoplasm disease stages as an independent risk factor for LUAD. Furthermore, the risk score shared a similar genomic and immune feature as PSMC genes, and high-risk tumors exhibited significant genomic and chromosomal instability, a higher TIDE score but lower immune score, and a decreased abundance of B and CD8+ T cells. Finally, high-risk patients were suggested to be less sensitive to immunotherapy but had a higher possibility of responding to platinum-based chemotherapy. The LUAD samples from the local cohort supported the difference in the expression levels of these five hub genes between tumor and normal tissues and the correlation between the risk score and PD-L1 expression. Conclusion: Overall, our results provide deep insight into PSMC genes in LUAD, especially the prognostic effect and related immune profile that may predict therapeutic responses.

BACKGROUND: Inferring historical population admixture events yield essential insights in understanding a species demographic history. Methods are available to infer admixture events in demographic history with extant genetic data from multiple sources. Due to the deficiency in ancient population genetic data, there lacks a method for admixture inference from a single source. Pairwise Sequentially Markovian Coalescent (PSMC) estimates the historical effective population size from lineage genomes of a single individual, based on the distribution of the most recent common ancestor between the diploid\'s alleles. However, PSMC does not infer the admixture event.
RESULTS: Here, we proposed eSMC, an extended PSMC model for admixture inference from a single source. We evaluated our model\'s performance on both in silico data and real data. We simulated population admixture events at an admixture time range from 5 kya to 100 kya (5 years/generation) with population admix ratio at 1:1, 2:1, 3:1, and 4:1, respectively. The root means the square error is [Formula: see text] kya for all experiments. Then we implemented our method to infer the historical admixture events in human, donkey and goat populations. The estimated admixture time for both Han and Tibetan individuals range from 60 kya to 80 kya (25 years/generation), while the estimated admixture time for the domesticated donkeys and the goats ranged from 40 kya to 60 kya (8 years/generation) and 40 kya to 100 kya (6 years/generation), respectively. The estimated admixture times were concordance to the time that domestication occurred in human history.
CONCLUSIONS: Our eSMC effectively infers the time of the most recent admixture event in history from a single individual\'s genomics data. The source code of eSMC is hosted at https://github.com/zachary-zzc/eSMC .

Migration is typically associated with risk and uncertainty at the population level, but little is known about its cost-benefit trade-offs at the species level. Migratory insects in particular often exhibit strong demographic fluctuations due to local bottlenecks and outbreaks. Here, we use genomic data to investigate levels of heterozygosity and long-term population size dynamics in migratory insects, as an alternative to classical local and short-term approaches such as regional field monitoring. We analyse whole-genome sequences from 97 Lepidoptera species and show that individuals of migratory species have significantly higher levels of genome-wide heterozygosity, a proxy for effective population size, than do nonmigratory species. Also, we contribute whole-genome data for one of the most emblematic insect migratory species, the painted lady butterfly (Vanessa cardui), sampled across its worldwide distributional range. This species exhibits one of the highest levels of genomic heterozygosity described in Lepidoptera (2.95 ± 0.15%). Coalescent modelling (PSMC) shows historical demographic stability in V. cardui, and high effective population size estimates of 2-20 million individuals 10,000 years ago. The study reveals that the high risks associated with migration and local environmental fluctuations do not seem to decrease overall genetic diversity and demographic stability in migratory Lepidoptera. We propose a \"compensatory\" demographic model for migratory r-strategist organisms in which local bottlenecks are counterbalanced by reproductive success elsewhere within their typically large distributional ranges. Our findings highlight that the boundaries of populations are substantially different for sedentary and migratory insects, and that, in the latter, local and even regional field monitoring results may not reflect whole population dynamics. Genomic diversity patterns may elucidate key aspects of an insect\'s migratory nature and population dynamics at large spatiotemporal scales.

The shimofuri goby (Tridentiger bifasciatus) is a small and highly adaptable goby, distributed along the coasts of China, the Sea of Japan, and the west coastal and estuarine areas of the Northwest Pacific. Next-generation sequencing was used to generate genome-wide survey data to provide essential characterization of the shimofuri goby genome and for the further mining of genomic information. The genome size of the shimofuri goby was estimated to be approximately 887.60 Mb through K-mer analysis, with a heterozygosity ratio and repeat sequence ratio of 0.47% and 32.60%, respectively. The assembled genome was used to identify microsatellite motifs (Simple Sequence Repeats, SSRs), extract single-copy homologous genes and assemble the mitochondrial genome. A total of 288,730 SSRs were identified. The most frequent SSRs were dinucleotide repeats (with a frequency of 61.15%), followed by trinucleotide (29.87%), tetranucleotide (6.19%), pentanucleotide (1.13%), and hexanucleotide repeats (1.66%). The results of the phylogenetic analysis based on single-copy homologous genes showed that the shimofuri goby and Rhinogobius similis can be clustered into one branch. The shimofuri goby was originally thought to be the same as the chameleon goby (Tridentiger trigonocephalus) due to their close morphological resemblance. However, a complete mitochondrial genome was assembled and the results of the phylogenetic analysis support the inclusion of the shimofuri goby as a separate species. PSMC analysis indicated that the shimofuri goby experienced a bottleneck event during the Pleistocene Glacial Epoch, in which its population size decreased massively, and then it began to recover gradually after the Last Glacial Maximum. This study provides a reference for the further assembly of the complete genome map of the shimofuri goby, and is a valuable genomic resource for the study of its evolutionary biology.