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Even sperm are “fine-tuned”? What now, Darwin?

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A friend writes to draw our attention to this new paper:

The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our single-cell transcriptomic data of human and mouse spermatogenesis provide evidence that this widespread transcription maintains DNA sequence integrity in the male germline by correcting DNA damage through a mechanism we term transcriptional scanning. 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 timescales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning shapes germline mutation signatures and modulates mutation rates in a gene-specific manner, maintaining DNA sequence integrity for the bulk of genes but allowing for faster evolution in a specific subset.

– Xia et al, Widespread Transcriptional Scanning in the Testis Modulates Gene Evolution Rates, Cell Volume 180, Issue 2, 23 January 2020, Pages 248-262.e21 (paywall)

Look, if they can’t even sell Darwinism to sperm, they need PR 911 pronto.

Here’s a bit from a paywalled a commentary:

Xia and colleagues show that heritable mutations are kept in check in the male germline partly by‘‘transcriptional scanning,’’ wherein the majority of genes are transcribed and therefore subject to transcription-coupled repair. They provide a new model for understanding the mechanisms ofgenome surveillance and evolution. Evolution, genetics, and cell biology collide in the male germline, with outcomes that can be both spectacular and puzzling. Male germ cells are tasked with shepherding the heritable genome through an array of assaults on genome integrity, including programmed double-strand breaks, homologous recombination between chromosomes, de-repression of transposable elements, and a near-complete repackaging of nuclear chromatin. At the same time, these cells must coordinate their own differentiation program to generate sperm, a highly specialized cell type whose function is absolutely required for reproductive fitness. Germline-specific mechanisms that shield the genome during theseevents include piRNAs, specialized com-ponents of the DNA damage machinery,and a lower threshold to activate apoptotic pathways (Walter et al.,2003). There are, however, many aspects of genome regulation in male germ cells that remain mysterious. One such phenomenon is the extreme complexity of the transcriptome during spermatogenesis: nearly the whole genome is expressed in testes, more than in any other cell type (Soumillon et al., 2013). In this issue of Cell, Xia et al. (2020) propose a new evolutionary explanation for this phenomenon: correction of heritable DNA damage by ‘‘transcriptional scanning.’’ The model they propose (Figure 1) provides a new framework for understanding genome regulation in the germline and for evaluating patterns of genome variation, mutation, and selection at the evolutionary and population levels.

– Bluma J. Lesch, Sperm Go to (Transcription) Extremes, https://doi.org/10.1016/j.cell.2019.12.033

Remember when the statue of Darwin got pride of place at that British Natural History Museum during the “200 years of Darwin” uproar in 2009? The statue of museum founder Richard Owen was booted to make way.

Would the boffins do that today? Even if they would, they would need a meatier explanation for their actions now. If the signature anniversary were a decade from now, they probably just wouldn’t do it.


See also: Nature Reviews Genetics Article Admits That Junk DNA Has Been “Prematurely Dismissed” But why, Johnny, why was it dismissed as junk at all? What general theory were the proponents of dismissal relying on? Why didn’t it work?

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