Revisiting the neutral dynamics derived limiting guanine-cytosine content using human de novo point mutation data

We revisit the topic of human genome guanine-cytosine (G+C) content and adenine-thymine (A+T) content under neutral evolution. For this study, the gold standard de novo mutation data within the human genome is used to estimate the mutation rates, instead of using base substitution data between related species. We define the rates (coefficients) of de novo mutation events, which are estimated solely from the mutation event data. Based on the de novo mutations collected from the intergenic regions of control samples, we are able to calculate the limiting content of any genomic quantities, by calculating the components of the normalized eigenvector corresponding to the largest eigenvalue of the transpose of the mutational rates matrix. When a 3-by-3 mutational rate matrix is used, accounting for the G+C content, A+T content, and CpG density, their neutral limit at time infinity is obtained. We observe that the G+C content in the currently G+C rich regions drops less severely than in the G+C poor regions. This provides a potential mechanism to retain the current spatial variation of G+C content (isochore-like structure), and to resist against homogenization.

Automated summary

This study reexamines the topic of G+C and A+T content in the human genome under neutral evolution, using de novo mutation data. The researchers observe that G+C content in G+C rich regions declines less severely compared to G+C poor regions, which suggests a potential mechanism for maintaining spatial variation in the genome.