转换突变
转换突变(Transition,简称Ts)是一种点突变,指DNA序列中嘌呤(A或G)互相转换或嘧啶(C或T)互相转换的突变[1],而嘌呤与嘧啶间的转换则称为颠换突变。一个核苷酸有两种颠换突变可能发生,仅有一种转换突变的可能,但后者发生的机率高于前者数倍[2],转换突变因摇摆碱基对之故而较少改变编码的胺基酸,可能因对基因的影响较小而较易被保留[3]。
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C-T突变
胞嘧啶(C)可自发去胺而转为脲嘧啶(U),后者可由尿嘧啶DNA糖基酶(UDG)切除(碱基切除修复)以阻止突变,若未在DNA复制前修复则会造成转换突变[4]。被甲基化的胞嘧啶(5-甲基胞嘧啶)发生去胺反应的机率更高,其去胺后转为胸腺嘧啶(T),可由胸腺嘧啶DNA糖苷酶(TDG)切除修复,若未及时修复也会发生转换突变[5](TDG亦可移除DNA中突变产生的脲嘧啶[6])。C-T突变是人类细胞中最常发生的突变,有数种癌症与这种突变有关[7],且造成人类基因组中的CpG位点出现频率低于期望值,此现象称为CG抑制[8]。
2020年,有研究统计发现CG抑制的程度和基因组大小成反比,并提出假说认为基因组演化过程中,细胞为抑制转位子表现而将其甲基化,使该处C-T突变的机率增加,可能进而变异产生强化子等具有新功能的序列[5]。
参考文献
- ^ Futuyma, D.J. Evolution 3rd. Sinauer. 2013. ISBN 978-1605351155.
- ^ Vogel F, Kopun M. Higher frequencies of transitions among point mutations.. J Mol Evol. 1977, 9 (2): 159–80. PMID 864721. doi:10.1007/BF01732746.
- ^ Guo C, McDowell IC, Nodzenski M, Scholtens DM, Allen AS, Lowe WL; et al. Transversions have larger regulatory effects than transitions.. BMC Genomics. 2017, 18 (1): 394. PMC 5438547 . PMID 28525990. doi:10.1186/s12864-017-3785-4.
- ^ Longo MC, Berninger MS, Hartley JL. Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. Gene. Sep 1990, 93 (1): 125–8. PMID 2227421. doi:10.1016/0378-1119(90)90145-H.
- ^ 5.0 5.1 Zhou, Wanding; Liang, Gangning; Molloy, Peter L.; Jones, Peter A. DNA methylation enables transposable element-driven genome expansion. Proceedings of the National Academy of Sciences of the United States of America. 11 August 2020, 117 (32): 19359–19366 [2021-04-23]. ISSN 1091-6490. PMC 7431005 . PMID 32719115. doi:10.1073/pnas.1921719117. (原始内容存档于2021-04-01).
- ^ Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL; et al. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.. Nat Chem Biol. 2012, 8 (4): 328–30. PMC 3307914 . PMID 22327402. doi:10.1038/nchembio.914.
- ^ Krokan HE, Drabløs F, Slupphaug G. Uracil in DNA--occurrence, consequences and repair.. Oncogene. 2002, 21 (58): 8935–48. PMID 12483510. doi:10.1038/sj.onc.1205996.
- ^ International Human Genome Sequencing Consortium; et al. Initial sequencing and analysis of the human genome (PDF). Nature. February 2001, 409 (6822): 860–921 [2021-04-23]. PMID 11237011. doi:10.1038/35057062. (原始内容 (PDF)存档于2020-07-29).