Hindawi Publishing Corporation
BioMed Research International
Volume 2013, Article ID 709042, 6 pages
http://dx.doi.org/10.1155/2013/709042
Research Article
CpGislandEVO: A Database and Genome Browser for
Comparative Evolutionary Genomics of CpG Islands
Guillermo Barturen,
1,2
Stefanie Geisen,
1,2
Francisco Dios,
1,2
E. J. Maarten Hamberg,
1,2
Michael Hackenberg,
1,2
and José L. Oliver
1,2
1
Departamento de Gen´ etica, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
2
Laborat´ orio de Bioinform´ atica, Instituto de Biotecnolog´ ıa, Centro de Investigaci´ on Biom´ edica, 18100 Granada, Spain
Correspondence should be addressed to Jos´ e L. Oliver; oliver@ugr.es
Received 20 April 2013; Revised 12 July 2013; Accepted 19 August 2013
Academic Editor: Stephan Koblm¨ uller
Copyright © 2013 Guillermo Barturen et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Hypomethylated, CpG-rich DNA segments (CpG islands, CGIs) are epigenome markers involved in key biological processes.
Aberrant methylation is implicated in the appearance of several disorders as cancer, immunodeiciency, or centromere instability.
Furthermore, methylation diferences at promoter regions between human and chimpanzee strongly associate with genes involved
in neurological/psychological disorders and cancers. herefore, the evolutionary comparative analyses of CGIs can provide insights
on the functional role of these epigenome markers in both health and disease. Given the lack of speciic tools, we developed
CpGislandEVO. Briely, we irst compile a database of statistically signiicant CGIs for the best assembled mammalian genome
sequences available to date. Second, by means of a coupled browser front-end, we focus on the CGIs overlapping orthologous
genes extracted from OrthoDB, thus ensuring the comparison between CGIs located on truly homologous genome segments. his
allows comparing the main compositional features between homologous CGIs. Finally, to facilitate nucleotide comparisons, we
lited genome coordinates between assemblies from diferent species, which enables the analysis of sequence divergence by direct
count of nucleotide substitutions and indels occurring between homologous CGIs. he resulting CpGislandEVO database, linking
together CGIs and single-cytosine DNA methylation data from several mammalian species, is freely available at our website.
1. Introduction
Short stretches of CpG dinucleotides (CpG islands or CGIs)
predominantly hypomethylated in healthy tissues [1, 2] are
key epigenomic markers in mammalian genomes [3]. Almost
all housekeeping genes and a half of the tissue-speciic genes
are associated to CGIs [4]. DNA methylation plays an impor-
tant role in the origin as well as in the function of CGIs. Aber-
rant methylation (mostly hypermethylation) of CGIs can
lead to several syndromes, such as cancer [5–10]. Moreover,
although it has been shown that certain human diseases may
have evolutionary epigenetic origins [11, 12], it remains largely
unknown how patterns of DNA methylation difer between
closely related species and whether such diferences con-
tribute to species-speciic phenotypes [11]. Some methylation
databases [13–15] and CGI databases [16] have been devel-
oped, but, to our knowledge, no existing genome browser
addresses speciically the evolutionary relationships between
the CGIs from diferent species. To help describing and
understanding the function as well as the mechanisms gen-
erating and maintaining CGIs within an evolutionary con-
text, we develop here CpGislandEVO (http://bioinfo2.ugr.es/
CpGislandEVO/index.php). he database, coupled to a pow-
erful genome browser, links together experimental and pre-
dicted CGIs, as well as single-cytosine-resolution DNA
methylation data from diferent mammalian species.
Early analyses of CGI evolution were based on compo-
sitional comparisons between islands from diferent species
but located on homologous gene contexts [17, 18]. Recently,
the rapidly increasing number of sequenced genomes enabled
evolutionary studies relying on multiple-sequence align-
ments [19]. Here, we combine both approaches to envisage
accurate sequence comparisons between CGIs located on
homologous gene contexts.