The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals1–6, probably owing to the evolutionary pressure on males to be reproductively successful7. However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from 11 species that cover the three main mammalian lineages (eutherians, marsupials and monotremes) and birds (the evolutionary outgroup), and include seven primates. We find that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions and new genes in late spermatogenic stages, probably facilitated by reduced pleiotropic constraints, haploid selection and transcriptionally permissive chromatin. We identify temporal expression changes of individual genes across species and conserved expression programs controlling ancestral spermatogenic processes. Genes predominantly expressed in spermatogonia (germ cells fuelling spermatogenesis) and Sertoli (somatic support) cells accumulated on X chromosomes during evolution, presumably owing to male-beneficial selective forces. Further work identified transcriptomal differences between X- and Y-bearing spermatids and uncovered that meiotic sex-chromosome inactivation (MSCI) also occurs in monotremes and hence is common to mammalian sex-chromosome systems. Thus, the mechanism of meiotic silencing of unsynapsed chromatin, which underlies MSCI, is an ancestral mammalian feature. Our study illuminates the molecular evolution of spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals.

The expansion of the neocortex, one of the hallmarks of mammalian evolution, was accompanied by an increase in the number of cerebellar neurons. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trace the development of the cerebellum from early neurogenesis to adulthood in human, mouse, and the marsupial opossum. Our cross-species analyses revealed that the cellular composition and differentiation dynamics throughout cerebellum development are largely conserved, except for human Purkinje cells. Global transcriptome profiles, conserved cell state markers, and gene expression trajectories across neuronal differentiation show that the cerebellar cell type-defining programs have been overall preserved for at least 160 million years. However, we also discovered differences. We identified 3,586 genes that either gained or lost expression in cerebellar cells in one of the species, and 541 genes that evolved new expression trajectories during neuronal differentiation. The potential functional relevance of these cross-species differences is highlighted by the diverged expression patterns of several human disease-associated genes. Altogether, our study reveals shared and lineage-specific programs governing the cellular development of the mammalian cerebellum, and expands our understanding of the evolution of mammalian organ development.

T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.