Decrypted function of junk DNA

Researchers determine the function of the supposed DNA waste

08/09/2012

Eleven years after the decoding of the human genome by the Human Genome Project, an international research team has taken another important step in understanding the blueprint of life. Hundreds of scientists from the ENCODE project, led by the National Genome Research Institute in the US and the EMBL-European Bioinformatics Institute in the UK, have now presented a detailed map of the functions of the human genome, identifying four million so-called gene switches.

Since decoding the human genome as part of the Human Genome Project more than a decade ago, molecular biologists around the world have wondered why only two percent of genes are composed of genes that guide protein formation. Theoretically, in the course of evolution, these supposedly useless components of the genome, also known as junk DNA, could have disappeared. But the junk DNA is by no means superfluous, it fulfills the researchers of the ENCODE project, a crucial regulatory function for the activity of genes. The scientists have published their results in more than 30 articles in the three renowned scientific journals "Nature", "Genome Biology" and "Genome Research".

Four million gene switches identified
For nine years, researchers worldwide have been working on the ENCODE project to study genomic regions outside the gene sequences used to construct proteins. They discovered a surprisingly far-reaching function of the junk DNA. Four million identified gene switches determine the activity of the genes. "Mutations in these regions can lead to human disease," reports the European Bioinformatics Institute in a recent press release. The number of identified gene switch is amazingly high, stressed the director of the institute, Rolf Apweiler. The junk DNA is actually a "control panel" with millions of controls that determine the activity of the genes. "80 percent of the genome is involved in some way in this regulation," write the researchers of the ENCODE project.

Identified gene switches in the junk DNA regulate gene activity
A total of 442 scientists from the United States, Great Britain, Spain, Singapore and Japan have been involved in the study of human genes in the past nine years as part of the ENCODE project. They sequenced over 1,600 genomes from 147 tissue types. They collected the huge amount of 15 terabytes of raw data, which were then analyzed. Initially, the researchers focused on the areas of the genome, which are directly responsible for the construction guide of the proteins. However, these were only two percent of the genome. The following investigations were devoted in particular to the analysis of so-called junk DNA. Here, scientists identified four million gene switches that contribute to the production of millions of different proteins via the regulation of gene activity. Each gene can be switched on and off, but also read in at least two to three different ways, explained the head of the European Bioinformatics Institute. These gene versions are called transcripts.

High complexity of gene switches makes it difficult to understand diseases
Dr. Michael Snyder, professor and chair of Stanford University and lead investigator at ENCODE, explained that the project provided the insights "that we need to look beyond the linear structure of the genome and recognize the whole network." ENCODE enables a deep Insight into the "loop that tells us how all parts come together to form a complex entity," Snyder continues. However, the result is fascinating and frustrating at the same time, added Rolf Apweiler. The complexity of the function of the four million gene switch is simply so high that a simple cause-and-effect relationship with regard to certain diseases is difficult to determine. The ultimate goal of the work is to help develop medicines that are cheaper, more effective and safer than today's. However, the development of diseases is far more complex than previously thought. Apweiler therefore wondered "if our brain cells ever will be enough" to understand how a disease develops and how to intervene in this process.

Deciphering the circuit diagram of life
Nevertheless, the scientists are convinced of the importance of their research results. The free publication of the data is a milestone in genome research. The ENCODE project is making a significant contribution "to understanding the human schematic," said Michael Snyder. In addition to the fundamental understanding of biology, it is also possible to use the data to investigate the study of genetic influences on the development of diseases. "We are beginning to understand the information generated in genome-wide association studies," says Snyder. Various studies comparing the genome of people with complex diseases, such as diabetes, heart disease, heart disease or obesity, to healthy individuals have been published. However, these have localized most of the differences outside the gene sequences responsible for protein formation.

Encyclopedia on the function of the genome
In light of the results of the ENCODE project, these genome-wide association studies appear in a completely different light, explained Rolf Apweiler. The attention now lies on the millions of gene switches, which apparently have significant influence on the development of diseases. While previously the regulatory elements were more likely to be found near the gene sequences that determine the formation of proteins, the researchers revealed in the course of the ENCODE project that the comparatively distant sections also play a role. According to the researchers, such a comprehensive analysis of the genome was made possible by significant advances in sequencing technology, which not only made genetic analysis faster but also much cheaper. "Deciphering the first human genome cost about 500 million euros, and nowadays one can decipher one's genetic make-up for 1 000 to 1 500 euros," said the head of the European Bioinformatics Institute. Thanks to the new possibilities, "we now have an interactive encyclopedia that everyone can refer to, which will make a big difference" in future research, according to the Spanish researcher Roderic Guigo from the Center de Regulació Genomica (CRG), who is also involved in the project. in Barcelona. (Fp)

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