Codon based co-occurrence network motifs in human mitochondria

Abstract

The nucleotide polymorphism in the human mitochondrial genome (mtDNA) tolled by codon position bias plays an indispensable role in human population dispersion and expansion. Herein, genome-wide nucleotide co-occurrence networks were constructed using data comprised of five different geographical regions and around 3000 samples for each region. We developed a powerful network model to describe complex mitochondrial evolutionary patterns among codon and non-codon positions. We found evidence that the evolution of human mitochondria DNA is dominated by adaptive forces, particularly mutation and selection, which was supported by many previous studies. The diversity observed in the mtDNA was compared with mutations, co-occurring mutations, network motifs considering codon positions as causing agent. This comparison showed that long-range nucleotide co-occurrences have a large effect on genomic diversity. Most notably, codon motifs apparently underpinned the preferences among codon positions for co-evolution which is probably highly biased during the origin of the genetic code. Our analysis also showed that variable nucleotide positions of different human sub-populations implemented the independent mtDNA evolution to its geographical dispensation. Ergo, this study has provided both a network framework and a codon glance to investigate co-occurring genomic variations that are critical in underlying complex mitochondrial evolution.