美国贝勒医学院Erez Lieberman Aiden等共同合作，近期取得重要工作进展。他们研究发现，在距今5.2万年的长毛猛犸象皮肤样本中仍存在三维基因组结构。相关研究成果2024年7月11日在线发表于《细胞》杂志上。

据介绍，对古代DNA的分析通常涉及对幸存的短寡核苷酸进行测序，并与相关现代物种的基因组组装进行比对。

研究人员发现，52000年前死亡的雌性猛犸象的皮肤保留了其古老的基因组结构。研究人员使用PaleoHi-C绘制染色质接触图并组装其基因组，得到28个染色体长度的支架。染色体区域、隔室、环、巴尔体和无活性X染色体（Xi）超结构域持续存在。猛犸象皮肤中的活性和非活性基因组区室比其他大象组织更像亚洲象皮肤。这一分析揭示了新的生物学。区室化的差异揭示了猛犸象和大象中转录可能发生改变的基因。

猛犸象Xi的结构是四分体，而不是像人和老鼠那样的二分体。研究人员假设，在这头猛犸象死亡后不久，样本在西伯利亚的寒冷中自发冷冻干燥，导致玻璃化转变，在纳米尺度上保存了古代染色体的亚化石。

附：英文原文

Title: Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

Author: Marcela Sandoval-Velasco, Olga Dudchenko, Juan Antonio Rodríguez, Cynthia Pérez Estrada, Marianne Dehasque, Claudia Fontsere, Sarah S.T. Mak, Ruqayya Khan, Vinícius G. Contessoto, Antonio B. Oliveira Junior, Achyuth Kalluchi, Bernardo J. Zubillaga Herrera, Jiyun Jeong, Renata P. Roy, Ishawnia Christopher, David Weisz, Arina D. Omer, Sanjit S. Batra, Muhammad S. Shamim, Neva C. Durand, Brendan O’Connell, Alfred L. Roca, Maksim V. Plikus, Mariya A. Kusliy, Svetlana A. Romanenko, Natalya A. Lemskaya, Natalya A. Serdyukova, Svetlana A. Modina, Polina L. Perelman, Elena A. Kizilova, Sergei I. Baiborodin, Nikolai B. Rubtsov, Gur Machol, Krisha Rath, Ragini Mahajan, Parwinder Kaur, Andreas Gnirke, Isabel Garcia-Trevio, Rob Coke, Joseph P. Flanagan, Kelcie Pletch, Aurora Ruiz-Herrera, Valerii Plotnikov, Innokentiy S. Pavlov, Naryya I. Pavlova, Albert V. Protopopov, Michele Di Pierro, Alexander S. Graphodatsky, Eric S. Lander, M. Jordan Rowley, Peter G. Wolynes, José N. Onuchic, Love Dalén, Marc A. Marti-Renom, M. Thomas P. Gilbert, Erez Lieberman Aiden

Issue&Volume: 2024/07/11

Abstract: Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

DOI: 10.1016/j.cell.2024.06.002

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00642-1