Die Evolution von Proteinbiosyntheseraten in Säugetieren
Bioinformatik und Theoretische Biologie
Evolutionäre Zell- und Entwicklungsbiologie der Tiere
Zusammenfassung der Projektergebnisse
A primary goal in biology is to understand the molecular basis of phenotypic evolution, most notably that of humans and other mammals. Most phenotypic differences between species are likely due to regulatory mutations that affect gene expression. Recent evolutionary transcriptome studies, based on high-throughput RNA sequencing data, have provided initial insights into mammalian gene expression evolution. Our own previous work, which was based on the first cross-mammalian transcriptome dataset, revealed general principles underlying gene expression evolution and its phenotypic implications. However, the expression output of protein-coding genes may be substantially affected by regulatory events that occur after transcription. Thus, our understanding of gene expression evolution has remained limited. In the framework of this new project, we investigated the evolution of protein synthesis rates in major organs (brain, liver, testis) across all major mammalian lineages (placental mammals, marsupials, egg-laying monotremes) based on a recently developed high-throughput approach (ribosome profiling) that measures translation at high resolution. Our integrated analyses of these “translatome” data and matched transcriptome data addressed long-standing hypotheses of mammalian gene expression evolution. First, we defined the full set of protein-coding regions in transcriptomes from the different organs and species and assessed their functional conservation. We were thus able to address key questions regarding the translation capacities of mammalian genomes and their evolutionary dynamics. For example, we assessed the frequency and functionality of new genes that emerged “from scratch” during evolution. Second, based on quantitative analyses, we investigated global patterns of gene expression evolution and underlying selective forces at the levels of both transcription and translation. In particular, our within-species analyses reveal that translational regulation is widespread in the different organs, in particular across the spermatogenic cell types of the testis. Moreover, we found that the between-species divergence in gene expression is substantially lower at the translatome layer than at the transcriptome layer owing to extensive buffering between the expression layers. Thus, mutational changes in gene expression regulation that arose during evolution were often balanced between the two layers, to ensure the production of unaltered amounts of proteins. Further analyses incorporating available mass spectrometry proteomics data allowed us to establish that the co-evolution of transcriptomes and translatomes is reflected at the proteome layer – the final gene expression layer that actually functionally matters. Altogether, the data and results obtained in this project uncovered co-evolutionary patterns and associated selective forces across the expression layers, and provide a resource for understanding their interplay in mammalian organs. Given that our study included humans, it also provided novel insights and perspectives on the molecular evolution that led to the unique biology of our own species. No major surprises were encountered in the course of the project. Overall, our results confirmed many of our original hypotheses, but included various unexpected findings, such as the fact that the testis both contains many genes under strong evolutionary constraint on gene expression as well as genes whose expression evolution was accelerated at the translatome layer. We also uncovered intriguing cases of new genes that may have contributed to the evolution of the human brain. A press release was issued by Heidelberg University with respect to our Nature paper (https://www.uni-heidelberg.de/de/newsroom/wie-sich-organfunktionen-im-laufe-der-evolution-herausgebildet-haben und https://www.eurekalert.org/pub_releases/2019-06/uoh-nog062519.php). Thus, our work has already been covered by some national and international online news outlet.
Projektbezogene Publikationen (Auswahl)
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Transcriptome and translatome co-evolution in mammals. (2020) Nature
Wang, Z.Y., Leushkin, E., Liechti, A., Ovchinnikova, S., Mößinger, K., Brüning, T., Rummel, C., Grützner, F., Cardoso-Moreira, M., Janich, P., Gatfield, D., Diagouraga, B., de Massy, B., Gill, M.E., Peters, A.H.F.M., Anders, S., and Kaessmann, H.
