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Comparative analysis using K-mer and K-flank patterns provides evidence for CpG island sequence evolution in mammalian genomes

Authors
Chae, HeejoonPark, JinwooLee, Seong-WhanNephew, Kenneth P.Kim, Sun
Issue Date
5월-2013
Publisher
OXFORD UNIV PRESS
Citation
NUCLEIC ACIDS RESEARCH, v.41, no.9, pp.4783 - 4791
Indexed
SCIE
SCOPUS
Journal Title
NUCLEIC ACIDS RESEARCH
Volume
41
Number
9
Start Page
4783
End Page
4791
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/103454
DOI
10.1093/nar/gkt144
ISSN
0305-1048
Abstract
CpG islands are GC-rich regions often located in the 5' end of genes and normally protected from cytosine methylation in mammals. The important role of CpG islands in gene transcription strongly suggests evolutionary conservation in the mammalian genome. However, as CpG dinucleotides are over-represented in CpG islands, comparative CpG island analysis using conventional sequence analysis techniques remains a major challenge in the epigenetics field. In this study, we conducted a comparative analysis of all CpG island sequences in 10 mammalian genomes. As sequence similarity methods and character composition techniques such as information theory are particularly difficult to conduct, we used exact patterns in CpG island sequences and single character discrepancies to identify differences in CpG island sequences. First, by calculating genome distance based on rank correlation tests, we show that k-mer and k-flank patterns around CpG sites can be used to correctly reconstruct the phylogeny of 10 mammalian genomes. Further, we used various machine learning algorithms to demonstrate that CpG islands sequences can be characterized using k-mers. In addition, by testing a human model on the nine different mammalian genomes, we provide the first evidence that k-mer signatures are consistent with evolutionary history.
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