Widespread haploid-biased gene expression in mammalian spermatogenesis associated with frequent selective sweeps and evolutionary conflict

Mendel’s first law dictates that alleles segregate randomly during meiosis and are distributed to offspring with equal frequency, requiring sperm to be functionally independent of their genetic payload. Developing mammalian spermatids have been thought to accomplish this by freely sharing RNA from virtually all genes through cytoplasmic bridges, equalizing allelic gene expression across different genotypes. Applying single cell RNA sequencing to developing spermatids, we identify a large class of mammalian genes whose allelic expression ratio is informative of the haploid genotype, which we call genoinformative markers (GIMs). 29% of spermatid-expressed genes in mice and 47% in non-human primates are not uniformly shared, and instead show a confident allelic expression bias of at least 2-fold towards the haploid genotype. This property of GIMs was significantly conserved between individuals and between rodents and primates. Consistent with the interpretation of specific RNA localization resulting in incomplete sharing through cytoplasmic bridges, we observe a strong depletion of GIM transcripts from chromatoid bodies, structures involved in shuttling RNA across cytoplasmic bridges, and an enrichment for 3’ UTR motifs involved in RNA localization. If GIMs are translated and functional in the context of fertility, they would be able to violate Mendel’s first law, leading to selective sweeps through a population. Indeed, we show that GIMs are enriched for signatures of positive selection, accounting for dozens of recent mouse, human, and primate selective sweeps. Intense selection at the sperm level risks evolutionary conflict between germline and somatic function, and GIMs show evidence of avoiding this conflict by exhibiting more testis-specific gene expression, paralogs, and isoforms than expression-matched control genes. The widespread existence of GIMs suggests that selective forces acting at the level of individual mammalian sperm are much more frequent than commonly believed.