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bioRxiv · 10.1101/2024.10.08.617222

Within-ejaculate haploid selection reduces disease biomarkers in human sperm

Marcu, D.·Cohen-Krais, J.·Godden, A.·Alavioon, G.·Martins, C.·Almstrup, K.·Saalbach, G.·Immler, S.
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Abstract

The germline is widely regarded as a checkpoint against the inheritance of damaged genomes, yet the mechanisms that could enact such filtering remain poorly resolved. Of the millions of sperm in a human ejaculate, only one fertilises the egg, creating a strong opportunity for selection among gametes. Combining within-ejaculate selection on sperm quality with whole-genome sequencing and proteomics in healthy donors, we find that this selection is biased against molecular signatures of age-related disease. The most reproducibly diverging genes are tumour suppressors, and genes diverging under sperm longevity-based selection are enriched for senescence-associated genes involved in genome maintenance and oxidative stress response. High-quality sperm are further depleted of inflammation- and cancer-associated proteins. This genomic signature is conserved in zebrafish, in which longer-lived sperm sire longer-lived offspring. We propose that within-ejaculate selection acts as a pre-fertilisation filter against age-related disease alleles, with implications for offspring lifespan and healthspan.

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Marcu, D., Cohen-Krais, J., Godden, A., Alavioon, G., Martins, C., Almstrup, K., Saalbach, G., Immler, S.. 2024-10-09. Within-ejaculate haploid selection reduces disease biomarkers in human sperm. https://doi.org/10.1101/2024.10.08.617222

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