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== CpG loss == CpG depletion has been observed in the process of DNA methylation of [[Transposable element|Transposable Elements]] (TEs) where TEs are not only responsible in the genome expansion but also CpG loss in a host DNA. TEs can be known as "methylation centers" whereby the methylation process, the TEs spreads into the flanking DNA once in the host DNA. This spreading might subsequently result in CpG loss over evolutionary time. Older evolutionary times show a higher CpG loss in the flanking DNA, compared to the younger evolutionary times. Therefore, the DNA methylation can lead eventually to the noticeably loss of CpG sites in neighboring DNA. <ref name=":0">{{Cite journal|last1=Zhou|first1=Wanding|last2=Liang|first2=Gangning|last3=Molloy|first3=Peter L.|last4=Jones|first4=Peter A.|date= 11 August 2020|title=DNA methylation enables transposable element-driven genome expansion|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=117|issue=32|pages=19359β19366|doi=10.1073/pnas.1921719117|issn=1091-6490|pmc=7431005|pmid=32719115|bibcode=2020PNAS..11719359Z |doi-access=free }}</ref> === Genome size and CpG ratio are negatively correlated === [[File:Genome Expansion.png|thumb|CpG methylation contributes to the genome expansion and consequently to CpG depletion. This picture shows a genome with no TEs and unmethylated CpG sites, and the insertion and transposition of a TE lead to methylation and silencing of the TE. Through the process of CpG methylation a decrease in CpG is found.<ref>{{cite journal|last1=Zhou|first1=Wanding|last2=Liang|first2=Gangning|last3=Molloy|first3=Peter L.|last4=Jones|first4=Peter A.|date=11 August 2020|title=DNA methylation enables transposable element-driven genome expansion|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=117|issue=32|pages=19359β19366|doi=10.1073/pnas.1921719117|issn=1091-6490|pmc=7431005|pmid=32719115|bibcode=2020PNAS..11719359Z |doi-access=free }}</ref>]] There is generally an inverse correlation between genome size and number of CpG islands, as larger genomes typically have a greater number of transposable elements. Selective pressure against TE's is substantially reduced if expression is suppressed via methylation, further TE's can act as "methylation centres" facilitating methylation of flanking DNA. Since methylation reduces selective pressure on nucleotide sequence long term methylation of CpG sites increases accumulation of spontaneous cytosine to thymine transitions, thereby resulting in a loss of Cp sites. <ref name=":0" /> ==== Alu elements as promoters of CpG loss ==== Alu elements are known as the most abundant type of transposable elements. Some studies have used Alu elements as a way to study the factors responsible for genome expansion. Alu elements are CpG-rich in a longer amount of sequence, unlike LINEs and ERVs. Alus can work as a methylation center, and the insertion into a host DNA can produce DNA methylation and provoke a spreading into the Flanking DNA area. This spreading is why there is considerable CpG loss and genome expansion.<ref name=":0" /> However, this is a result that is analyzed over time because older Alu elements show more CpG loss in sites of neighboring DNA compared to younger ones.
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