Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing.

Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees

A genome assembly of the American black bear, Ursus americanus, from California

The American black bear, Ursus americanus, is a widespread and ecologically important species in North America. In California, the black bear plays an important role in a variety of ecosystems and serves as an important species for recreational hunting. While research suggests that the populations in California are currently healthy, continued monitoring is critical, with genomic analyses providing an important surveillance tool. Here we report a high-quality, near chromosome-level genome assembly from a U. americanus sample from California. The primary assembly has a total length of 2.5 Gb contained in 316 scaffolds, a contig N50 of 58.9 Mb, a scaffold N50 of 67.6 Mb, and a BUSCO completeness score of 96%. This U. americanus genome assembly will provide an important resource for the targeted management of black bear populations in California, with the goal of achieving an appropriate balance between the recreational value of black bears and the maintenance of viable populations. The high quality of this genome assembly will also make it a valuable resource for comparative genomic analyses among black bear populations and among bear species

Multi-regional Sequencing Analysis Reveals Extensive Genetic Heterogeneity in Gastric Tumors from Latinos

Gastric cancer is a leading cause of cancer mortality and health disparities in Latinos. We evaluated gastric intratumoral heterogeneity using multiregional sequencing of >700 cancer genes in 115 tumor biopsies from 32 patients, 29 who were Latinos. Analyses focused on comparisons with The Cancer Genome Atlas (TCGA) and on mutation clonality, druggability, and signatures. We found that only approximately 30% of all mutations were clonal and that only 61% of the known TCGA gastric cancer drivers harbored clonal mutations. Multiple clonal mutations were found in new candidate gastric cancer drivers such as EYS, FAT4, PCDHA1, RAD50, EXO1, RECQL4, and FSIP2. The genomically stable (GS) molecular subtype, which has the worse prognosis, was identified in 48% of our Latino patients, a fraction that was >2.3-fold higher than in TCGA Asian and White patients. Only a third of all tumors harbored clonal pathogenic mutations in druggable genes, with most (93%) GS tumors lacking actionable clonal mutations. Mutation signature analyses revealed that, in microsatellite-stable (MSS) tumors, DNA repair mutations were common for both tumor initiation and progression, while tobacco, POLE, and inflammation signatures likely initiate carcinogenesis. MSS tumor progression was likely driven by aging- and aflatoxin-associated mutations, as these latter changes were usually nonclonal. In microsatellite-unstable tumors, nonclonal tobacco-associated mutations were common. Our study, therefore, contributed to advancing gastric cancer molecular diagnostics and suggests clonal status is important to understanding gastric tumorigenesis. Our findings of a higher frequency of a poor prognosis associated molecular subtype in Latinos and a possible new aflatoxin gastric cancer etiology also advance cancer disparities research.SignificanceOur study contributes to advancing our knowledge of gastric carcinogenesis, diagnostics, and cancer health disparities

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing.

Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing

Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees

A draft reference genome of the red abalone, Haliotis rufescens , for conservation genomics

Red abalone, Haliotis rufescens, are herbivorous marine gastropods that primarily feed on kelp. They are the largest and longest-lived of abalone species with a range distribution in North America from central Oregon, United States, to Baja California, MEX. Recently, red abalone have been in decline as a consequence of overharvesting, disease, and climate change, resulting in the closure of the commercial fishery in the 1990s and the recreational fishery in 2018. Protecting this ecologically and economically important species requires an understanding of their current population dynamics and connectivity. Here, we present a new red abalone reference genome as part of the California Conservation Genomics Project (CCGP). Following the CCGP genome strategy, we used Pacific Biosciences HiFi long reads and Dovetail Omni-C data to generate a scaffold-level assembly. The assembly comprises 616 scaffolds for a total size of 1.3 Gb, a scaffold N50 of 45.7 Mb, and a BUSCO complete score of 97.3%. This genome represents a significant improvement over a previous assembly and will serve as a powerful tool for investigating seascape genomic diversity, local adaptation to temperature and ocean acidification, and informing management strategies

A chromosome-level reference genome for the giant pink sea star, Pisaster brevispinus , a species severely impacted by wasting

Efforts to protect the ecologically and economically significant California Current Ecosystem from global change will greatly benefit from data about patterns of local adaptation and population connectivity. To facilitate that work, we present a reference-quality genome for the giant pink sea star, Pisaster brevispinus, a species of ecological importance along the Pacific west coast of North America that has been heavily impacted by environmental change and disease. We used Pacific Biosciences HiFi long sequencing reads and Dovetail Omni-C proximity reads to generate a highly contiguous genome assembly of 550 Mb in length. The assembly contains 127 scaffolds with a contig N50 of 4.6 Mb and a scaffold N50 of 21.4 Mb; the BUSCO completeness score is 98.70%. The P. brevispinus genome assembly is comparable to the genome of the congener species P. ochraceus in size and completeness. Both Pisaster assemblies are consistent with previously published karyotyping results showing sea star genomes are organized into 22 autosomes. The reference genome for P. brevispinus is an important first step toward the goal of producing a comprehensive, population genomics view of ecological and evolutionary processes along the California coast. This resource will help scientists, managers, and policy makers in their task of understanding and protecting critical coastal regions from the impacts of global change

Reference genome for the American rubyspot damselfly, Hetaerina americana

Damselflies and dragonflies (Order: Odonata) play important roles in both aquatic and terrestrial food webs and can serve as sentinels of ecosystem health and predictors of population trends in other taxa. The habitat requirements and limited dispersal of lotic damselflies make them especially sensitive to habitat loss and fragmentation. As such, landscape genomic studies of these taxa can help focus conservation efforts on watersheds with high levels of genetic diversity, local adaptation, and even cryptic endemism. Here, as part of the California Conservation Genomics Project (CCGP), we report the first reference genome for the American rubyspot damselfly, Hetaerina americana, a species associated with springs, streams and rivers throughout California. Following the CCGP assembly pipeline, we produced two de novo genome assemblies. The primary assembly includes 1,630,044,487 base pairs, with a contig N50 of 5.4 Mb, a scaffold N50 of 86.2 Mb, and a BUSCO completeness score of 97.6%. This is the seventh Odonata genome to be made publicly available and the first for the subfamily Hetaerininae. This reference genome fills an important phylogenetic gap in our understanding of Odonata genome evolution, and provides a genomic resource for a host of interesting ecological, evolutionary, and conservation questions for which the rubyspot damselfly genus Hetaerina is an important model system

A highly contiguous genome assembly for the pocket mouse Perognathus longimembris longimembris

The little pocket mouse, Perognathus longimembris, and its nine congeners are small heteromyid rodents found in arid and seasonally arid regions of Western North America. The genus is characterized by behavioral and physiological adaptations to dry and often harsh environments, including nocturnality, seasonal torpor, food caching, enhanced osmoregulation, and a well-developed sense of hearing. Here we present a genome assembly of Perognathus longimembris longimembris generated from PacBio HiFi long read and Omni-C chromatin-proximity sequencing as part of the California Conservation Genomics Project. The assembly has a length of 2.35 Gb, contig N50 of 11.6 Mb, scaffold N50 of 73.2 Mb, and includes 93.8% of the BUSCO Glires genes. Interspersed repetitive elements constitute 41.2% of the genome. A comparison with the highly endangered Pacific pocket mouse, P. l. pacificus, reveals broad synteny. These new resources will enable studies of local adaptation, genetic diversity, and conservation of threatened taxa