The study, published June 9 in Nature Genetics, provides evidence for a 40-year-old hypothesis that regulation of genes must play an important role in evolution since there is little difference between humans and chimps in the proteins produced by genes. Indeed, human and chimpanzee proteins are more than 99 percent identical.
The researchers showed that the number of evolutionary adaptations to the part of the machinery that regulates genes, called transcription factor binding sites, may be roughly equal to adaptations to the genes themselves.
“This is the most comprehensive and most direct analysis to date of the evolution of gene regulatory sequences in humans,” said senior author Adam Siepel, Cornell associate professor of biological statistics and computational biology.
“It’s taken these 40 years to get a clear picture of what’s going on in these sequences because we haven’t had the data until very recently,” said Leonardo Arbiza, a postdoctoral researcher in Siepel’s lab and the paper’s lead author.
Less than 2 percent of the human genome – the complete set of genetic material – contains genes that code for proteins. In cells, these proteins are instrumental in biological pathways that affect an organism’s health, appearance and behavior.
Much less is known about the remaining 98 percent of the genome; however, in the 1960s, scientists recognized that some of the non-protein coding DNA regulates when and where genes are turned on and off, and how much protein they produce. The regulatory machinery works when proteins called transcription factors bind to specific short sequences of DNA that flank the gene, called transcription factor binding sites, and by doing so, switch genes on and off.
Among the findings, the study reports that when compared with protein coding genes, binding site DNA shows close to three times as many “weakly deleterious mutations,” that is, mutations that may weaken or make an individual more susceptible to disease, but are generally not severe. Weakly deleterious mutations exist in low frequencies in a population and are eventually weeded out over time. These mutations are responsible for many inherited human diseases.
While genes generally tend to resist change, a mutation occasionally leads to a favorable trait and increases across a population; this is called positive selection. By contrast, “transcription factor binding sites show considerable amounts of positive selection,” said Arbiza, with evidence for adaptation in binding sites that regulate genes controlling blood cells, brain function and immunity, among others.
“The overall picture shows more evolutionary flexibility in the binding sites than in protein coding genes,” said Siepel. “This has important implications for how we think about human evolution and disease.”
This is one of the first studies to combine recent data that identifies transcription factor binding sites, data on human genetic variation and genome comparisons between humans and apes. A new computational method called INSIGHT (Inference of Natural Selection from Interspersed Genomically coHerent elemenTs), designed by Ilan Gronau, a postdoctoral researcher in Siepel’s lab and a co-author of the study, allowed the scientists to integrate these diverse data types and find evidence of natural selection in the regulatory DNA.
“Transcription factor binding sites are probably the regulatory elements we know the most about,” said Arbiza. “If you want to understand evolution of gene expression regulation, that’s a good starting point.”
INSIGHT may now be used by other researchers for analyzing other short regulatory DNA sequences, such as micro-RNAs, non-coding molecules that also play a role in gene regulation.
The study was funded by the Packard Foundation, Alfred P. Sloan Foundation, National Science Foundation, National Institutes of Health, and a fellowship from the Cornell Center for Vertebrate Genomics.
Cornell University has television and ISDN radio studios available for media interviews.
John Carberry | Newswise
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences