Widespread transcriptional scanning in the testis modulates gene evolution ratesLibrarian's Comment : Almost 90% of all protein coding genes are expressed, at least at the RNA level, during human spermatogenesis. Why do developing male germ cells express so many genes is a long-standing mystery in Andrology. This widespread expression is typically considered a consequence of the extreme remodeling sperm DNA is subjected to during spermatogenesis. Such remodeling has been shown to be essential for the differentiation of functionally competent mature gametes, and defects in this process can lead to male infertility. Yet, in this paper, an intriguing new possibility is put forward to explain why developing germ cells express so many genes. According to the Authors, male germ cells use this widespread expression to correct lesions in their DNA and, therefore, avoid the transmission of harmful mutations to the next generation. This process, previously described in other cellular contexts, is called transcription-coupled repair, and allows developing sperm cells to use their gene expression machinery to scan for DNA damage and trigger its efficient repair. Yet, like so many processes in nature, this one also seems to require a very precise balance: in genes expressed at very high levels during spermatogenesis, repair is surprisingly ineffective as it cannot compensate for the damage introduced by the underlying elevated expression. These thought-provoking observations will certainly add to the on-going debate of why fathers are the preferential source of new mutations in human populations.
Published in : Biorxiv
Authors : 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 finding that has long puzzled molecular biologists. Analyzing our single-cell transcriptomic maps of human and mouse spermatogenesis, we provide 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. Moreover, this effect is fine-tuned by the level of gene expression during spermatogenesis. The unexpressed genes, which in our model do not benefit from transcriptional scanning, diverge faster over evolutionary time-scales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning modulates germline mutation rates in a gene-specific manner, maintaining DNA sequence integrity for the bulk of genes but allowing for fast evolution in a specific subset.
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