A large-scale study by molecular biologists at the University of Heidelberg has yielded innovative new results on the evolution and regulation of gene expression in mammalian organs. Thus, we find out how the functions of the organs were modeled during human evolution.
Scientists have investigated RNA synthesis and subsequent protein synthesis in the organs of humans and other representative mammals and, using sequencing technologies, analyzed more than one hundred billion fragments of gene expression in various organs. They were able to demonstrate that the fine interaction of the two synthesis processes during evolution was crucial for shaping the functions of the organs.
A complex interaction of activity between a large number of genes – known as gene expression – explains the functions of organs
“Until now, our understanding of these essential genetic programs in mammals was limited to the first layer of genetic expression – the production of messenger RNA,” explains Prof. Dr. Henrik Kaessmann, group leader in research “Functional evolution of the mammalian genome.” team from the Center for Molecular Biology at the University of Heidelberg (ZMBH). The next layer – the effective synthesis of ribosome proteins by translating messenger RNAs – has remained largely unknown.
Heidelberg researchers have now studied this second synthesis process more closely. Using so-called next-generation sequencing technologies, they analyzed the gene expression of various organs on both layers.
Thus, they studied the brain, liver, and testicles of selected humans and other mammals, including rhesus monkeys, mice, opossums, and platypus. “Based on these data, we could investigate both layers of gene expression together and compare them between mammalian organs, using state-of-the-art bioinformatics approaches,” explains Dr. Evgeny Leushkin of ZMBH.
In their large-scale study, ZMBH researchers showed that the fine interaction of the two synthesis processes during evolution was critical for modeling organ functions.
For the first time, they were able to show that – in addition to regulating messenger RNA production – other mechanisms of regulation at the level of translation are crucial for optimizing the amount of protein produced in all organs.
This is especially true in the testicles, where translational regulation is essential for sperm development. Another important finding concerns the mutational changes in the regulation of gene expression that occurred during evolution. These changes have often been balanced between the two layers. The mutually compensating changes were maintained, first and foremost, to ensure the production of substantial amounts of protein.
Researchers from France and Switzerland contributed to the study. Funding was provided by the German Research Foundation and the European Research Council. The data is available in a publicly accessible database, and research results were published in the journal Nature.