Strand Asymmetries Across Genomic Processes

Across biological systems, a number of genomic processes, including transcription, replication, DNA repair, and transcription factor binding, display intrinsic directionalities. These directionalities are reflected in the asymmetric distribution of nucleotides, motifs, genes, transposon integration sites, and other functional elements across the two complementary strands. Strand asymmetries, including GC skews and mutational biases, have shaped the nucleotide composition of diverse organisms. The investigation of strand asymmetries often serves as a method to understand underlying biological mechanisms, including protein binding preferences, transcription factor interactions, retrotransposition, DNA damage and repair preferences, transcription-replication collisions, and mutagenesis mechanisms. Research into this subject also enables the identification of functional genomic sites, such as replication origins and transcription start sites. Improvements in our ability to detect and quantify DNA strand asymmetries will provide insights into diverse functionalities of the genome, the contribution of different mutational mechanisms in germline and somatic mutagenesis, and our knowledge of genome instability and evolution, which all have significant clinical implications in human disease, including cancer. In this review, we describe key developments that have been made across the field of genomic strand asymmetries, as well as the discovery of associated mechanisms.