Transcriptome and translatome co-evolution in mammals

Abstract

Gene expression programs define shared and species-specific phenotypes, but their evolution remains largely uncharacterized beyond the transcriptome layer 1 . Here we report an analysis of the co-evolution of translatomes and transcriptomes using ribosome-profling and matched RNA-sequencing data for three organs (brain, liver and testis) in fve mammals (human, macaque, mouse, opossum and platypus) and a bird (chicken). Our within-species analyses reveal that translational regulation is widespread in the diferent organs, in particular across the spermatogenic cell types of the testis. The between-species divergence in gene expression is around 20% lower at the translatome layer than at the transcriptome layer owing to extensive buffering between the expression layers, which especially preserved old, essential and housekeeping genes. Translational upregulation specifcally counterbalanced global dosage reductions during the evolution of sex chromosomes and the efects of meiotic sex-chromosome inactivation during spermatogenesis. Despite the overall prevalence of bufering, some genes evolved faster at the translatome layer—potentially indicating adaptive changes in expression; testis tissue shows the highest fraction of such genes. Further analyses incorporating mass spectrometry proteomics data establish that the co-evolution of transcriptomes and translatomes is refected at the proteome layer. Together, our work uncovers co-evolutionary patterns and associated selective forces across the expression layers, and provides a resource for understanding their interplay in mammalian organs.

Preferential Ribosome Loading on the Stress-Upregulated mRNA Pool Shapes the Selective Translation under Stress Conditions

“…Moreover, the comparative transcriptome (mRNAs) and translatome (RPFs) analysis in human primary hepatocytes under hypoxia demonstrated that translational responses preceded and were predominant over transcriptional responses [16]. Remarkably, a recent study [18], using Ribo-seq and matched RNA-seq data to compare transcriptome (mRNAs) and translatome (RPFs) in three primary organs across five representative mammals and a bird, uncovered the differential regulation and coevolution between the two expression layers, thus providing a substantial insight into their interplay in mammalian organs. These studies revealed the complexity of coordination between transcriptome (mRNAs) and translatome (RPFs) both in yeasts and mammals.…”

“…Recent years have also seen a substantial interest in dissecting the relationship between transcriptional and translational regulations in yeasts, plants and mammals under diverse stresses or across different tissues [15][16][17][18][19][20][21][22][23][24]. However, most of these studies assess the mRNA translation through polysome profiling, which cannot measure the exact number of ribosomes loading on polysome-associated mRNAs for each gene [19][20][21][22][23].…”

“…However, most of these studies assess the mRNA translation through polysome profiling, which cannot measure the exact number of ribosomes loading on polysome-associated mRNAs for each gene [19][20][21][22][23]. By contrast, a few studies comprehensively investigated the translatome based on ribosome footprints [15][16][17][18]24]. For instance, one study in yeast observed that under severe stress conditions such as amino acid depletion or osmotic shock, changes in the transcriptome (mRNAs) correlated well with those in translatome (RPFs), while hardly any or relatively poor correlations were found between these two levels in response to mild stresses induced by calcofluor-white and menadione [15].…”

Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

“…This holds especially true at the transcriptional level, where selection can be weak and result in genetic drift and concerted transcriptome evolution. [12][13][14][15][16] Accordingly, identification of so-called 'species signals', rather than functionally relevant gene expression changes, can dominate differential expression analyses, particularly when applied to similar cell types over long evolutionary distances. 12,17 Moreover, any given cell type might occur in a variety of so-called 'cell states', related to e.g.…”

Widespread translational control regulates retinal development in mouse

“…Increasing evidence emphasizes the importance of translation of gene expression [13][14][15]. Dynamic, tight, and coordinated translational regulation can conduce to the growth of multicellular organisms, particularly during a rapid morphological transition, such as development of red blood cell [16], embryonic stem cell differentiation [17], cortical neurogenesis [18], myogenic differentiation [19], and spermioteleosis [20]. In addition, it is suggested that translational regulation might influence plasticity of visual pathway development and function [21].…”