CpG island density and its correlations with genomic features in mammalian genomes

Abstract

Background: CpG islands, which are clusters of CpG dinucleotides in GC-rich regions, are considered gene markers and represent an important feature of mammalian genomes. Previous studies of CpG islands have largely been on specific loci or within one genome. To date, there seems to be no comparative analysis of CpG islands and their density at the DNA sequence level among mammalian genomes and of their correlations with other genome features.

Results: In this study, we performed a systematic analysis of CpG islands in ten mammalian genomes. We found that both the number of CpG islands and their density vary greatly among genomes, though many of these genomes encode similar numbers of genes. We observed significant correlations between CpG island density and genomic features such as number of chromosomes, chromosome size, and recombination rate. We also observed a trend of higher CpG island density in telomeric regions. Furthermore, we evaluated the performance of three computational algorithms for CpG island identifications. Finally, we compared our observations in mammals to other non-mammal vertebrates.

Conclusion: Our study revealed that CpG islands vary greatly among mammalian genomes. Some factors such as recombination rate and chromosome size might have influenced the evolution of CpG islands in the course of mammalian evolution. Our results suggest a scenario in which an increase in chromosome number increases the rate of recombination, which in turn elevates GC content to help prevent loss of CpG islands and maintain their density. These findings should be useful for studying mammalian genomes, the role of CpG islands in gene function, and molecular evolution.

Figure 1

Correlations between CGI density and genomic features in nine mammalian genomes. The platypus chromosomes were excluded because of incomplete genome sequence data and chromosome data. (a) CGI density (per Mb) versus number of chromosome pairs. (b) CGI density (per Mb) versus log₁₀(chromosome size). The Y chromosomes were excluded because of insufficient data. (c) CGI density (per Mb) versus chromosome GC content (%). (d) CGI density (per Mb) versus chromosome Obs_CpG/Exp_CpG.

Figure 2

Correlation between CGI density and recombination rate (cM/Mb) in the human genome; a 5 Mb window was used.

Figure 3

Distribution of CGI density (per Mb) on human chromosome 8. The data indicate a trend of higher CGI density in telomeric regions.

Figure 4

CGI density comparison between mammals and non-mammals. This figure shows the distribution of CGI density (per Mb) versus chromosome GC content (%). (a) Comparison of four groups in mammals. (b) Comparison of mammals, chicken and fish.

Figure 5

Correlation between CGI density and other genetic factors. (a) Significant correlation between CGI density and body temperature. (b) Insignificant correlation between CGI density and lifespan.