Author: Bo Xia, Yun Yan, Maayan Baron, Florian Wagner, Dalia Barkley, Marta Chiodin, Sang Y. Kim, David L. Keefe, Joseph P. Alukal, Jef D. Boeke, Itai Yanai
Abstract: The testis expresses the largest number of genes of any mammalian organ, a findingthat has long puzzled molecular biologists. Our single-cell transcriptomic data ofhuman and mouse spermatogenesis provide evidence that this widespread transcriptionmaintains DNA sequence integrity in the male germline by correcting DNA damage througha mechanism we term transcriptional scanning. We find that genes expressed duringspermatogenesis display lower mutation rates on the transcribed strand and have lowdiversity in the population. Moreover, this effect is fine-tuned by the level of geneexpression during spermatogenesis. The unexpressed genes, which in our model do notbenefit from transcriptional scanning, diverge faster over evolutionary timescalesand are enriched for sensory and immune-defense functions. Collectively, we proposethat transcriptional scanning shapes germline mutation signatures and modulates mutationrates in a gene-specific manner, maintaining DNA sequence integrity for the bulk ofgenes but allowing for faster evolution in a specific subset.