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Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection,we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.
Shared mammalian traits include lactation, hair and relatively large brains with unique structures1. In addition to these traits, individual lineages have evolved distinct anatomical, physiological and behavioural characteristics relating to differences in reproduction, life span, cognitive abilities and disease susceptibility. The molecular changes underlying these phenotypic shifts and the associated selective pressures have begun to be investigated using available mammalian genomes2, the number of which is rapidly increasing. However, although genome analyses may uncover protein-coding changes that potentially underlie phenotypic alterations, regulatory mutations affecting gene expression probably explain many or even most phenotypic differences between species3.
Until recently, comparisons of mammalian transcriptomes were essentially restricted to closely related primates4-8 or mice5, although human-mouse comparisons using microarrays were also attempted9. Nevertheless, microarrays require hybridization to species-specific probes, making between-species comparisons of transcript abundance difficult6. The development of RNA sequencing (RNA-seq) protocols now allows for accurate and sensitive assessments of expression levels10. The power of RNA-seq for transcriptome assessment was recently demonstrated for human individuals11,12 and closely related primates13,14.
RNA-seq and genome reannotation
To study mammalian transcriptome evolution at high resolution, we generated RNA-seq data (,3.2 billion Illumina Genome Analyser IIx reads of 76 base pairs) for the polyadenylated RNA fraction of brain (cerebral cortex or whole brain without cerebellum), cerebellum, heart, kidney, liver and testis (usually...