Division of Evolutionary Biology, Faculty of Biology, LMU Munich, München, Germany.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Mol Ecol Resour. 2021 Oct;21(7):2455-2470. doi: 10.1111/1755-0998.13443. Epub 2021 Jun 27.
With the advent of chromatin-interaction maps, chromosome-level genome assemblies have become a reality for a wide range of organisms. Scaffolding quality is, however, difficult to judge. To explore this gap, we generated multiple chromosome-scale genome assemblies of an emerging wild animal model for carcinogenesis, the California sea lion (Zalophus californianus). Short-read assemblies were scaffolded with two independent chromatin interaction mapping data sets (Hi-C and Chicago), and long-read assemblies with three data types (Hi-C, optical maps and 10X linked reads) following the "Vertebrate Genomes Project (VGP)" pipeline. In both approaches, 18 major scaffolds recovered the karyotype (2n = 36), with scaffold N50s of 138 and 147 Mb, respectively. Synteny relationships at the chromosome level with other pinniped genomes (2n = 32-36), ferret (2n = 34), red panda (2n = 36) and domestic dog (2n = 78) were consistent across approaches and recovered known fissions and fusions. Comparative chromosome painting and multicolour chromosome tiling with a panel of 264 genome-integrated single-locus canine bacterial artificial chromosome probes provided independent evaluation of genome organization. Broad-scale discrepancies between the approaches were observed within chromosomes, most commonly in translocations centred around centromeres and telomeres, which were better resolved in the VGP assembly. Genomic and cytological approaches agreed on near-perfect synteny of the X chromosome, and in combination allowed detailed investigation of autosomal rearrangements between dog and sea lion. This study presents high-quality genomes of an emerging cancer model and highlights that even highly fragmented short-read assemblies scaffolded with Hi-C can yield reliable chromosome-level scaffolds suitable for comparative genomic analyses.
随着染色质相互作用图谱的出现,广泛的生物的染色体水平基因组组装已经成为现实。然而,支架质量很难判断。为了探索这一差距,我们生成了加利福尼亚海狮(Zalophus californianus)这一新兴癌症模型动物的多个染色体水平基因组组装。使用两种独立的染色质相互作用图谱数据集(Hi-C 和芝加哥)进行短读序列组装,使用 Hi-C、光学图谱和 10X 连锁读取三种数据类型进行长读序列组装,遵循“脊椎动物基因组计划(VGP)”管道。在这两种方法中,18 个主要支架都恢复了染色体组型(2n=36),支架 N50 分别为 138 和 147Mb。与其他鳍足类基因组(2n=32-36)、雪貂(2n=34)、红熊猫(2n=36)和家犬(2n=78)的染色体水平的同线性关系在两种方法中都是一致的,并恢复了已知的分裂和融合。使用 264 个整合到基因组中的单基因犬细菌人工染色体探针的多色染色体平铺和染色体涂染,对基因组组织进行了独立评估。在染色体内部观察到方法之间存在广泛的差异,最常见于着丝粒和端粒周围的易位,在 VGP 组装中这些易位得到了更好的解决。基因组和细胞学方法在 X 染色体的近完美同线性上达成一致,并结合起来,允许对犬和海狮之间的常染色体重排进行详细研究。本研究提供了一种新兴癌症模型的高质量基因组,并强调了即使是用 Hi-C 支架组装的高度碎片化的短读序列也可以产生适合比较基因组分析的可靠染色体水平支架。