Seeing evolution happening before your eyes

October 14, 2020

Animal diversity and evolution are driven by changes in how our genetic code is expressed. Specific DNA sequences called enhancers control where, when and how strongly genes are expressed during development to create the respective organism. Studying enhancers and how they result in different patterns of gene expression therefore helps us to understand more about how evolution takes place. In addition to driving the evolution of species, enhancers are also relevant to disease: mutations in enhancers are associated with over 80% of all human diseases.

"What we see in terms of biodiversity in nature is caused, to a large degree, by changes in enhancers," explains Justin Crocker, group leader at EMBL Heidelberg. "Understanding - and subsequently trying to predict - evolution in the time of climate change, where many animals are under the pressure to adapt quickly to fast changing environments, is an important task."

Despite broad relevance to evolution and disease, researchers still struggle to understand how enhancers are coded in our genomes and how easy it is to reprogram them, for example to prevent or treat diseases. In an attempt to learn more about enhancers, the Crocker group from EMBL Heidelberg performed an extensive study, published in Nature, on a specific enhancer in the model organism Drosophila melanogaster, a species of fruit fly. The group discovered that this enhancer - which controls the patterns where hair grows on flies - contains a lot more information than expected.

"Whenever we changed a single letter of the enhancer DNA sequence, we created a significant change to the pattern of gene expression it drove," explains Timothy Fuqua, PhD student at EMBL and first author of the paper. "We also found that almost all mutations to the enhancer alter the gene expression pattern in multiple ways. For example, one mutation controls not only where the expression pattern is within the fly, but also when, and how much of the gene was expressed."

These results were surprising and contradict what had previously been known about enhancers. Researchers thought that these complex gene expression patterns were created by different proteins attaching to the enhancer. A first clue that this might not be true came when Crocker and his team discovered that artificially-produced enhancers did not work as designed. Their most recent results provide support for this idea. "The results showed that developmental enhancers encode a much higher level of information than previously appreciated," Crocker says. "When we received the data, I was honestly shocked! I couldn't believe it and we repeated everything, as we assumed that there has been a mistake."

Importantly, the density of information encoded within the enhancer also constrains how animals can evolve. The study also showed that each possible mutation has a certain possibility for happening. This gives scientists insights into where evolution could lead. "We can use this information to predict patterns in wild fruit flies. Something which has been incredibly difficult to do so far," Fuqua says. "Our results should encourage the community to reassess our assumption about how these regions contribute to human health."

While studying enhancers is a well-established field in molecular biology, this study is unique in the sheer number of mutations having been studied. The group created more than 700 unique, randomly generated mutations within a single enhancer. "Nobody ever has studied so many enhancer variants at this level of depth before. It was as if evolution was happening before our very eyes!" highlights Fuqua. To perform so many experiments, the team built - assisted by the Janelia Research Campus and the Advanced Light Microscopy Facility at EMBL - a robot to handle the fly embryos used in the study, and an automated microscope pipeline to take images of each mutated line.

"Our study shows that what we have known about enhancers was oversimplified. It shows we have to study enhancers at much greater detail than ever before," Fuqua says. Therefore, in the next step, the team not only wants to expand the pipeline and its throughput, but also plans to study other enhancers and see if they can observe similar effects. "Can what we found be applied to other enhancers or not? We don't know yet. But we plan to find out," concludes Crocker.
-end-


European Molecular Biology Laboratory

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.