Widespread transcriptional scanning in the testis modulates gene evolution rates

The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our detailed transcriptomic map of human and mouse spermatogenesis provides evidence that this widespread transcription serves to maintain DNA sequence integrity in the male germline by correcting DNA damage through “transcriptional scanning”. Supporting this model, we find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population, while unexpressed genes evolve faster and are enriched for sensory and immune-defense functions. Thus, we propose that transcriptional scanning modulates mutation rates in a gene-specific manner, maintaining germline DNA sequence integrity for the bulk of genes but allowing for fast evolution in a specific subset. Overall design: The project contains data from single cell RNA-seq of both human (two biological replicates, each with two technical replicates) and mouse (two biological replicates) testicular cells.