High-resolution genome-wide profiling reveals intricate relationship between DNA damage and sperm physiology

Little is known about genome-wide profiles of different types of DNA damage in spermatozoa and how they relate to sperm quality. In this study, we for the first time constructed and analyzed high-resolution profiles of two very common DNA lesions in normal human sperm. We found non-random genomic distributions of the DNA lesions and a very complex relationship between DNA damage and sperm quality that depends on the type of DNA lesion and genomic location. We connected intricate details of genomic patterns of DNA damage with physiological properties of cells. We found an intriguing relationship between single-nucleotide hotspots of DNA damage and naturally occurring sequence variants, suggesting that certain regions of the genome are more prone to DNA damage which can lead to heritable sequence change. These results highlight complex relationship between DNA damage and cellular physiology which calls for more exploration of high-resolution genome-wide patterns of various DNA lesions.