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：1992
卷号：89
期号：3
页码：957-961
DOI：10.1073/pnas.89.3.957
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The development of nearest-neighbor analysis led to the finding that the frequency of the dinucleotide CpG is markedly depressed in vertebrates. One explanation of this suppression is that methylation of CpG found in vertebrates represents a mutational hot spot through deamination of methylcytidine to thymidine. We have examined the role of methylated CpG as a factor in CpG suppression by comparing CpG distributions in coding regions of 121 genes from six species, three with methylated DNA and three with nonmethylated DNA. Overall base composition shows that all species exhibit CpG suppression, with the methylated forms showing significantly greater suppression than nonmethylated forms. When the data are analyzed by CpG position, the mean values of the methylated forms exhibit greater suppression than nonmethylated forms at positions I-II and II-III, but there is considerable overlap of suppression scores for individual species. At position III-I, CpG suppression is marked in all methylated species, and it is reversed in all nonmethylated species. Our analysis supports the hypothesis that CpG patterns at positions II-III and III-I in methylated forms are affected by mutation acting through deamination of methylcytidine to thymidine. We speculate that the excess of CpGs at position III-I in nonmethylated forms may be related to a requirement for minimal thermal stability of the DNA.
