Abstract
BackgroundMammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait.ResultsHere we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that biased gene conversion (BGC) has been playing a role in within-genome GC content variation. Yet, a distinct contribution to GC content evolution is accounted for by a selective process. Accordingly, we searched for independent evidences that GC content distribution does not conform to neutral expectations. Indeed, after correcting for possible biases, we show that intron GC content and size display isochore-specific correlations.ConclusionWe consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and BGC in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes. This view might reconcile previous contrasting findings and add some theoretical background to recent evidences suggesting that GC content domains display different behaviors with respect to highly regulated biological processes such as developmentally-stage related gene expression and programmed replication timing during neural stem cell differentiation.
Highlights
Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains
We consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and biased gene conversion (BGC) in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes
We analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that both biased gene conversion (BGC) and selection have been playing a role in GC content variation
Summary
Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. BMC Evolutionary Biology 2008, 8:99 http://www.biomedcentral.com/1471-2148/8/99 of the human genome [2] indicated that the isochore model might need slight revision in that long regions are less compositionally homogeneous than previously thought and transitions at composition domains less sharp, so that the term "GC-content domain" was proposed instead of "isochore". The scientific debate is still open as to whether such a compositional heterogeneity is a selected or neutral trait and different hypothesis have been proposed [3,4]. The model conceives of GC content variation as a by-product of recombination and, supported by extensive evidence [8,9,10,11,12,13], its ability to explain isochore formation and maintenance has recently been criticized on different grounds. A positive effect of increased coding sequence GC content on transcriptional efficiency has recently been experimentally demonstrated [25]
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