文章基本信息

标题：Conservation of chromatin conformation in carnivores
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作者：Marco Corbo ; Joana Damas ; Madeline G. Bursell 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：9
DOI：10.1073/pnas.2120555119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance We found the three-dimensional (3D) structure of chromatin at the chromosome level to be highly conserved for more than 50 million y of carnivore evolution. Intrachromosomal contacts were maintained even after chromosome rearrangements within carnivore lineages, demonstrating that the maintenance of 3D chromatin architecture is essential for conserved genome functions. These discoveries enabled the identification of orthologous chromosomal DNA segments among related species, a method we call 3D comparative scaffotyping. The method has application for putative chromosome assignment of chromosome-scale DNA sequence scaffolds produced by de novo genome sequencing. Broadly applied to biodiversity genome sequencing efforts, the approach can reduce costs associated with karyotyping and the physical mapping of DNA segments to chromosomes. High throughput chromatin conformation capture (Hi-C) of leukocyte DNA was used to investigate the evolutionary stability of chromatin conformation at the chromosomal level in 11 species from three carnivore families: Felidae, Canidae, and Ursidae. Chromosome-scale scaffolds (C-scaffolds) of each species were initially used for whole-genome alignment to a reference genome within each family. This approach established putative orthologous relationships between C-scaffolds among the different species. Hi-C contact maps for all C-scaffolds were then visually compared and found to be distinct for a given reference chromosome or C-scaffold within a species and indistinguishable for orthologous C-scaffolds having a 1:1 relationship within a family. The visual patterns within families were strongly supported by eigenvectors from the Hi-C contact maps. Analysis of Hi-C contact maps and eigenvectors across the three carnivore families revealed that most cross-family orthologous subchromosomal fragments have a conserved three-dimensional (3D) chromatin structure and thus have been under strong evolutionary constraint for ∼54 My of carnivore evolution. The most pronounced differences in chromatin conformation were observed for the X chromosome and the red fox genome, whose chromosomes have undergone extensive rearrangements relative to other canids. We also demonstrate that Hi-C contact map pattern analysis can be used to accurately identify orthologous relationships between C-scaffolds and chromosomes, a method we termed “3D comparative scaffotyping.” This method provides a powerful means for estimating karyotypes in de novo sequenced species that have unknown karyotype and no physical mapping information.
关键词：enchromatin conformationchromosome evolutioncarnivoresmammals