{"id":32992,"date":"2020-10-14T17:00:22","date_gmt":"2020-10-14T15:00:22","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=32992"},"modified":"2024-03-22T10:55:04","modified_gmt":"2024-03-22T09:55:04","slug":"fruit-fly-enhancer","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/fruit-fly-enhancer\/","title":{"rendered":"Seeing evolution happening before your eyes"},"content":{"rendered":"\n

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 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.<\/p>\n\n\n\n

\u201cWhat we see in terms of biodiversity in nature is caused, to a large degree, by changes in enhancers,\u201d explains Justin Crocker, group leader at EMBL Heidelberg. \u201cUnderstanding \u2013 and subsequently trying to predict \u2013 evolution in the time of climate change, where many animals are under pressure to adapt quickly to fast-changing environments, is an important task.\u201d<\/p>\n\n\n\n

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<\/a> from EMBL Heidelberg performed an extensive study, published in Nature<\/em>, on a specific enhancer in the model organism Drosophila melanogaster<\/em>, a species of fruit fly. The group discovered that this enhancer \u2013 which controls the patterns where hair grows on flies \u2013 contains a lot more information than expected.<\/p>\n\n\n\n

\u201cWhenever we changed a single letter of the enhancer DNA sequence, we created a significant change to the pattern of gene expression it drove,\u201d explains Timothy Fuqua, a PhD student at EMBL and first author of the paper. \u201cWe 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.\u201d<\/p>\n\n\n\n

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. \u201cThe results showed that developmental enhancers encode a much higher level of information than previously appreciated,\u201d Crocker says. \u201cWhen we received the data, I was honestly shocked! I couldn\u2019t believe it and we repeated everything, as we assumed that there has been a mistake.\u201d<\/p>\n\n\n\n

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 of occurring. This gives scientists insights into where evolution could lead. \u201cWe can use this information to predict patterns in wild fruit flies: something which has been incredibly difficult to do so far,\u201d Fuqua says. \u201cOur results should encourage the community to reassess our assumption about how these regions contribute to human health.\u201d<\/p>\n\n\n\n

While studying enhancers is a well-established field in molecular biology, this study is unique in the sheer number of mutations that have been studied. The group created more than 700 unique, randomly generated mutations within a single enhancer. \u201cNobody ever has studied so many enhancer variants at this level of depth before. It was as if evolution was happening before our very eyes!\u201d says Fuqua. To perform so many experiments, the team built \u2013 assisted by the Janelia Research Campus<\/a> and the Advanced Light Microscopy Facility at EMBL<\/a> \u2013 a robot to handle the fly embryos used in the study, and an automated microscope pipeline to take images of each mutated line.<\/p>\n\n\n\n

\u201cOur 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,\u201d 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. \u201cCan what we found be applied to other enhancers or not? We don\u2019t know yet. But we plan to find out,\u201d concludes Crocker.<\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers from EMBL Heidelberg have established an automated pipeline to create mutations in genomic enhancers, letting them watch evolution unfold before their eyes.<\/p>\n","protected":false},"author":71,"featured_media":33196,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[5104,528,552,31,833],"embl_taxonomy":[19191],"class_list":["post-32992","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-almf","tag-crocker","tag-enhancer","tag-evolution","tag-fruit-fly","embl_taxonomy-crocker-group"],"acf":{"featured":true,"show_featured_image":false,"color":"#007B53","link_color":"#fff","article_intro":"

EMBL researchers find DNA enhancers more complex than previously thought<\/p>\n","related_links":[{"link_description":"Crocker group","link_url":"https:\/\/www.embl.de\/research\/units\/dev_biology\/crocker\/"},{"link_description":"Janelia Research Campus","link_url":"https:\/\/www.janelia.org\/"},{"link_description":"ALMF","link_url":"https:\/\/www.embl.de\/services\/core_facilities\/almf\/"}],"article_sources":[{"source_description":"

Timothy Fuqua et al<\/em>. Dense and pleiotropic regulatory information in a developmental enhancer. Nature<\/em>, published on 14 October 2020
\nDOI: 10.1038\/s41586-020-2816-5<\/p>\n","source_link_url":"https:\/\/www.nature.com\/articles\/s41586-020-2816-5"}],"in_this_article":false,"youtube_url":"https:\/\/www.youtube.com\/embed\/gt_Ji5N1VtE","mp4_url":"","video_caption":"This 3D video of a fruit fly embryo was taken using the confocal microscope imaging pipeline that the Crocker group and the Advanced Light Microscopy Facility at EMBL Heidelberg developed. Green marks cells that will produce hairs and magenta marks the pattern that is controlled by a specific enhancer sequence the group studied. 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