生物谷報道：南京大學(xué)田大成課題組20日在頂級雜志nature在線發(fā)表研究論文“Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes”,。這是南京大學(xué)首次作為通信單位發(fā)表nature論文。
變異熱點常見于遺傳序列和人體特定疾病發(fā)生的位點,，但是這種現(xiàn)象發(fā)生的機理并不十分明確,。南京大學(xué)科學(xué)家通過對六種獨立物種基因組的研究，加入或剪切單個核苷酸后比較發(fā)現(xiàn),，在單個核苷酸插入或剪切位點附近100個核苷酸也較易發(fā)生改變,。結(jié)果表明單個核苷酸插入或剪切會使其臨近序列也具有很高的變異率。
田大成解釋說,，基因突變主要是指DNA中核苷酸順序,、種類和數(shù)量的改變，而DNA序列中普遍存在的點（堿基）突變是遺傳變異的基本來源,。點突變又分為自發(fā)突變和誘發(fā)突變,。長期以來，學(xué)術(shù)界對自發(fā)突變機制的經(jīng)典認識是,，自發(fā)突變受一系列因素的影響,，是一系列變化的結(jié)果，具有隨機性和稀有性,。但隨著上個世紀90年代以來DNA測序技術(shù)的突破性進展，研究者們對自發(fā)突變在基因組中的數(shù)量和分布有了精確估計,，并普遍認為“自發(fā)突變在基因組中不是隨機分布的,，突變熱點普遍存在于基因組中”。這一結(jié)論對傳統(tǒng)的自發(fā)突變隨機性和稀有性的認識形成巨大挑戰(zhàn),，而這種現(xiàn)象也引起了各國科學(xué)家的極大關(guān)注,，但遺憾的是始終沒有找到一種普遍的機制來解釋這一重大的科學(xué)疑問。
田大成等發(fā)現(xiàn)的遺傳突變新機制具有重大科學(xué)意義,，成功破解了生物遺傳學(xué)上的很多懸念：第一,，基因組各區(qū)域的突變率很不相同，自發(fā)突變的數(shù)量是由Indel的數(shù)量和密度所決定,，自發(fā)突變的數(shù)量在Indel附近并不稀有,，遠離Indel的區(qū)域是稀有的，但Indel本身是一種點突變,，其發(fā)生有一定的隨機性,，因而其誘發(fā)的突變也有一定的隨機性,；第二，找到了多數(shù)自發(fā)突變的發(fā)生根源,，也就是說,，生物多樣性的最初變異來源，主要是由Indel誘導(dǎo)產(chǎn)生,；第三,，自然選擇在很大程度上是通過對Indel的選擇而實現(xiàn)，而自發(fā)突變率的高低很大程度上也是自然選擇的結(jié)果,；第四,，生物通過調(diào)節(jié)自身變異能力而適應(yīng)環(huán)境的能力，比人們原先想象的要大得多,，即突變在進化中的作用相當(dāng)巨大,。（生物谷Bioon.com）
推薦閱讀：人民的科學(xué)家——生物谷專訪南大教授田大成
生物谷推薦原始出處：
Nature , | doi:10.1038/nature07175; Received 19 January 2008; Accepted 17 June 2008; Published online 20 July 2008
Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes
Dacheng Tian1,4, Qiang Wang1,4, Pengfei Zhang1, Hitoshi Araki1,2, Sihai Yang1, Martin Kreitman3, Thomas Nagylaki3, Richard Hudson3, Joy Bergelson1,3 & Jian-Qun Chen1
State Key Laboratory of Pharmaceutical Biotechnology, Department of Biology, Nanjing University, Nanjing 210093, China
Department of Fish Ecology and Evolution, EAWAG Center of Ecology, Evolution and Biogeochemistry, 6047 Kastanienbaum, Switzerland
Department of Ecology & Evolution, University of Chicago, Chicago, Illinois 60637, USA
These authors contributed equally to this work.
Abstract
Mutation hotspots are commonly observed in genomic sequences and certain human disease loci1, 2, 3, 4, 5, 6, 7, but general mechanisms for their formation remain elusive7, 8, 9, 10, 11. Here we investigate the distribution of single-nucleotide changes around insertions/deletions (indels) in six independent genome comparisons, including primates, rodents, fruitfly, rice and yeast. In each of these genomic comparisons, nucleotide divergence (D) is substantially elevated surrounding indels and decreases monotonically to near-background levels over several hundred bases. D is significantly correlated with both size and abundance of nearby indels. In comparisons of closely related species, derived nucleotide substitutions surrounding indels occur in significantly greater numbers in the lineage containing the indel than in the one containing the ancestral (non-indel) allele; the same holds within species for single-nucleotide mutations surrounding polymorphic indels. We propose that heterozygosity for an indel is mutagenic to surrounding sequences, and use yeast genome-wide polymorphism data to estimate the increase in mutation rate. The consistency of these patterns within and between species suggests that indel-associated substitution is a general mutational mechanism.
