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古代DNA的损伤与修复

Damage and repair of ancient DNA.

作者信息

Mitchell David, Willerslev Eske, Hansen Anders

机构信息

The University of Texas MD Anderson Cancer Center, Department of Carcinogenesis, P.O. Box 389, Park Road 1C, Smithville, TX 78957, USA.

出版信息

Mutat Res. 2005 Apr 1;571(1-2):265-76. doi: 10.1016/j.mrfmmm.2004.06.060.

Abstract

Under certain conditions small amounts of DNA can survive for long periods of time and can be used as polymerase chain reaction (PCR) substrates for the study of phylogenetic relationships and population genetics of extinct plants and animals, including hominids. Because of extensive DNA degradation, these studies are limited to species that lived within the past 10(4)-10(5) years (Late Pleistocene), although DNA sequences from 10(6) years have been reported. Ancient DNA (aDNA) has been used to study phylogenetic relationships of protists, fungi, algae, plants, and higher eukaryotes such as extinct horses, cave bears, the marsupial wolf, the moa, and Neanderthal. In the past few years, this technology has been extended to the study of infectious disease in ancient Egyptian and South American mummies, the dietary habits of ancient animals, and agricultural practices and population dynamics of early native Americans. Hence, ancient DNA contains information pertinent to numerous fields of study including evolution, population genetics, ecology, climatology, medicine, archeology, and behavior. The major obstacles to the study of aDNA are its extremely low yield, contamination with modern DNA, and extensive degradation. In the course of this review, we will discuss the current aDNA literature describing the importance of aDNA studies as they relate to important biological questions and the difficulties associated with extracting useful information from highly degraded and damaged substrates derived from limited sources. In addition, we will present some of our own preliminary and published data on mechanisms of DNA degradation and some speculative thoughts on strategies for repair and restoration of aDNA.

摘要

在某些条件下,少量的DNA能够长期存活,并可作为聚合酶链反应(PCR)的底物,用于研究已灭绝动植物(包括原始人类)的系统发育关系和群体遗传学。由于DNA大量降解,这些研究仅限于过去10⁴-10⁵年(晚更新世)内生存的物种,尽管已有报道称获得了来自10⁶年前的DNA序列。古DNA(aDNA)已被用于研究原生生物、真菌、藻类、植物以及高等真核生物(如已灭绝的马、洞熊、袋狼、恐鸟和尼安德特人)的系统发育关系。在过去几年中,这项技术已扩展到研究古埃及和南美木乃伊中的传染病、古代动物的饮食习惯以及早期美洲原住民的农业实践和人口动态。因此,古DNA包含了与众多研究领域相关的信息,包括进化、群体遗传学、生态学、气候学、医学、考古学和行为学。研究aDNA的主要障碍是其产量极低、受到现代DNA的污染以及大量降解。在本综述过程中,我们将讨论当前的aDNA文献,描述aDNA研究与重要生物学问题相关的重要性以及从有限来源获得的高度降解和受损底物中提取有用信息所面临的困难。此外,我们将展示一些我们自己关于DNA降解机制的初步和已发表的数据,以及一些关于aDNA修复和恢复策略的推测性想法。

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