Liyun Yuan

Spotting off-targets from gene editing Unintended genomic modifications limit the potential therapeutic use of gene-editing tools. Available methods to find off-targets generally do not work in vivo or detect single-nucleotide changes. Three papers in this issue report new methods for monitoring gene-editing tools in vivo (see the Perspective by Kempton and Qi). Wienert et al. followed the recruitment of a DNA repair protein to DNA breaks induced by CRISPR-Cas9, enabling unbiased detection of off-target editing in cellular and animal models. Zuo et al. identified off-targets without the interference of natural genetic heterogeneity by injecting base editors into one blastomere of a two-cell mouse embryo and leaving the other genetically identical blastomere unedited. Jin et al. performed whole-genome sequencing on individual, genome-edited rice plants to identify unintended mutations. Cytosine, but not adenine, base editors induced numerous single-nucleotide variants in both mouse and rice. Science , this issue p. 286 , p. 289 , p. 292 ; see also p. 234

The domestic Bactrian camels were treated as one of the principal means of locomotion between the eastern and western cultures in history. However, whether they originated from East Asia or Central Asia remains elusive. To address this question, we perform whole-genome sequencing of 128 camels across Asia. The extant wild and domestic Bactrian camels show remarkable genetic divergence, as they were split from dromedaries. The wild Bactrian camels also contribute little to the ancestry of domestic ones, although they share close habitat in East Asia. Interestingly, among the domestic Bactrian camels, those from Iran exhibit the largest genetic distance and the earliest split from all others in the phylogeny, despite evident admixture between domestic Bactrian camels and dromedaries living in Central Asia. Taken together, our study support the Central Asian origin of domestic Bactrian camels, which were then immigrated eastward to Mongolia where native wild Bactrian camels inhabit.

The National Genomics Data Center (NGDC) provides a suite of database resources to support worldwide research activities in both academia and industry. With the rapid advancements in higher-throughput and lower-cost sequencing technologies and accordingly the huge volume of multi-omics data generated at exponential scales and rates, NGDC is continually expanding, updating and enriching its core database resources through big data integration and value-added curation. In the past year, efforts for update have been mainly devoted to BioProject, BioSample, GSA, GWH, GVM, NONCODE, LncBook, EWAS Atlas and IC4R. Newly released resources include three human genome databases (PGG.SNV, PGG.Han and CGVD), eLMSG, EWAS Data Hub, GWAS Atlas, iSheep and PADS Arsenal. In addition, four web services, namely, eGPS Cloud, BIG Search, BIG Submission and BIG SSO, have been significantly improved and enhanced. All of these resources along with their services are publicly accessible at https://bigd.big.ac.cn.

Background: Animal domestication has been extensively studied, but the process of feralization remains poorly understood. Results: Here, we performed whole-genome sequencing of 99 sheep and identified a primary genetic divergence between 2 heterogeneous populations in the Tibetan Plateau, including 1 semi-feral lineage. Selective sweep and candidate gene analysis revealed local adaptations of these sheep associated with sensory perception, muscle strength, eating habit, mating process, and aggressive behavior. In particular, a horn-related gene, RXFP2, showed signs of rapid evolution specifically in the semi-feral breeds. A unique haplotype and repressed horn-related tissue expression of RXFP2 were correlated with higher horn length, as well as spiral and horizontally extended horn shape. Conclusions: Semi-feralization has an extensive impact on diverse phenotypic traits of sheep. By acquiring features like those of their wild ancestors, semi-feral sheep were able to regain fitness while in frequent contact with wild surroundings and rare human interventions. This study provides a new insight into the evolution of domestic animals when human interventions are no longer dominant.