{"id":56006,"date":"2023-02-08T10:00:00","date_gmt":"2023-02-08T09:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=56006"},"modified":"2023-02-06T09:57:52","modified_gmt":"2023-02-06T08:57:52","slug":"new-evolutionary-insights-from-stepping-outside-the-lab","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/new-evolutionary-insights-from-stepping-outside-the-lab\/","title":{"rendered":"New evolutionary insights from stepping outside the lab"},"content":{"rendered":"\n<p>Justin Crocker is a scientist who loves embryos. So much so, he has been <a href=\"https:\/\/www.embl.org\/news\/lab-matters\/1117_emblcurious_questions\/\">known to collect<\/a> spider embryos in the woods around EMBL and marvel at their beautiful developmental patterns under the microscope.&nbsp;<\/p>\n\n\n\n<p>\u201cSeeing embryos developing and growing, understanding how the same coordinated process happens every time, is just incredible,\u201d said Crocker, who set up his lab in EMBL Heidelberg in 2017.<\/p>\n\n\n\n<p>Using fruit-fly embryos and a variety of other model systems, Crocker and his team have been demonstrating the importance of moving beyond standardised laboratory conditions and challenging established assumptions when it comes to understanding the development and evolution of phenotypes.&nbsp;<\/p>\n\n\n\n<p>Phenotypes are the observable characteristics of an organism \u2013 features such as behaviour, appearance, metabolism, gene expression patterns, etc. They result from interactions between the genotype \u2013 the information contained in DNA, and the environment. In two new<a href=\"https:\/\/europepmc.org\/article\/MED\/36516782\"> publications<\/a>, the Crocker group and their collaborators provide novel insights into some of the key processes that determine the robustness of phenotypes and the appearance of new phenotypes during development.&nbsp;<\/p>\n\n\n\n<p>This knowledge can help researchers better understand how diversity emerges during evolution in animals, and perhaps even predict ecological and environmental patterns of change in the phenotypes of wild animal populations.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Using \u2018natural\u2019 conditions to study epigenetic regulation of phenotypes<\/strong><\/h2>\n\n\n\n<p>The phenotypes any organism exhibits often depend on precise decisions regarding which genes are expressed where and when. These decisions are in turn influenced by \u2018epigenetic marks\u2019 \u2013 chemical signatures on DNA and DNA-binding proteins that can determine how \u2018accessible\u2019 a particular gene is for expression at a given point in time. The Crocker group became interested in one such epigenetic mark, called H3K4 monomethylation.&nbsp;<\/p>\n\n\n\n<p>\u201cThis epigenetic mark is present throughout the genome, but its deletion seems to have little to no impact on gene expression, which led scientists to hypothesise that it doesn\u2019t play a major role in normal development and function,\u201d said Albert Tsai, team leader at the Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), former postdoc in the Crocker lab, and co-first author of <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2211124722017247?via%3Dihub\">the first study, published in <em>Cell Reports<\/em><\/a>.&nbsp;<\/p>\n\n\n\n<p>H3K4 monomethylation is found ubiquitously in almost every cell\u2019s nucleus, and especially on enhancers \u2013 regulatory DNA regions that modulate where and how much a gene is expressed. \u201cThat led us to question why there is such an evolutionary drive to create these marks if it\u2019s actually doing nothing,\u201d said Tsai. The Crocker group was sure that they were missing something.&nbsp;<\/p>\n\n\n\n<p>Through experiments co-led by Lautaro Gandara, an EIPOD postdoc working across the Crocker and Alexandrov Groups, the team discovered that the role for H3K4 monomethylation can be better appreciated if one were to study the effects under more &#8216;natural&#8217; environmental contexts.&nbsp;<\/p>\n\n\n\n<p>Biologists often study organisms under well-standardised laboratory conditions to ensure rigour and reproducibility. However, this also increases the risk of missing effects that only become apparent outside of these narrow ranges of conditions.<\/p>\n\n\n\n<p>The Crocker group studied a variety of phenotypes in a fruit-fly strain with genetically reduced levels of H3K4 monomethylation throughout the genome, exposing the bugs to both standard and non-standard laboratory conditions. They found that the loss of this epigenetic mark led to changes in behaviour, gene expression, metabolism, and even rates of offspring production, especially when the fruit flies were fed on natural food sources, including fruit collected in and around the EMBL campus. When exposed to high temperatures or when certain background genes were mutated, the organisms likewise responded differently.&nbsp;<\/p>\n\n\n\n<p>\u201cIn the absence of this mark, certain traits became sensitive to environmental conditions and to different genetic backgrounds,\u201d said Gandara. \u201cThis demonstrates how intertwined these epigenetic marks can be with the regulatory layer of environmental perturbations.\u201d<\/p>\n\n\n\n<p>\u201cIt challenges the current paradigm of standardising experiments as much as possible to focus on very specific conditions,\u201d said Tsai. \u201cWe need to come up with controlled ways of bringing more natural environments into the lab.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Synthetic biology to explore how new phenotypes emerge<\/h2>\n\n\n\n<p>In the <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1534580722008474?via%3Dihub\">second study, published in <em>Developmental Cell<\/em><\/a>, Crocker and his team questioned how new phenotypes emerge in the first place. This is a central question in evolutionary biology \u2013 for organisms to accumulate small changes that would be selected by the environment, there must be a way to continuously, quickly, and easily introduce variation in phenotypes.&nbsp;<\/p>\n\n\n\n<p>While our genomes often accumulate small changes \u2013 called mutations \u2013 over time, these don\u2019t always result in changes in phenotypes, or observable traits. \u201cWe wanted to understand how much variations in genotypes translate to variations in phenotypes,\u201d said Rafael Galupa, first author of the paper and former postdoc in the Crocker lab. Galupa is currently on his way to establishing his independent lab in Centre de Biologie Int\u00e9grative, Toulouse (France).<\/p>\n\n\n\n<p>The team began by studying the expression of various genes in fruit-fly embryos with point mutations \u2013 single-nucleotide DNA changes \u2013 in enhancer regions of the genome.&nbsp;<\/p>\n\n\n\n<p>\u201cWhat we quickly started to appreciate was that while gene expression levels changed in these mutants, it always remained within the same regions,\u201d said Galupa. In other words, if a gene is usually active in the gut, for example, its expression levels increased or decreased as a result of the mutations, but did not shift to a different tissue, e.g. the muscle. \u201cSo we started wondering, what does it take to get expression elsewhere?\u201d said Galupa. \u201cUltimately in the course of evolution, how do you get new functions?\u201d<\/p>\n\n\n\n<p>It was at this point that the researchers took an innovative leap of logic, and decided to test what happens if instead of selectively creating mutations in the enhancers, one introduces completely random sequences into the genome instead. To their surprise, with this synthetic DNA approach, they found that random sequences easily drove gene expression, and in all parts of the embryo.<\/p>\n\n\n\n<p>In a natural context, random DNA sequences may arise in the genome due to viruses, or transposons \u2013 mobile genetic elements that actively move between different parts of the genome.&nbsp;<\/p>\n\n\n\n<p>\u201cWe have been talking about doing this for a long time, and everybody thought it was a bit crazy. Then we just went ahead and did it,\u201d said Crocker. \u201cIn the field, we often think about how expression is generated, how to activate genes, etc. This study makes us think that if any random sequence can drive expression, and we have a genome with millions of sequences \u2013 maybe the question is not so much how do you generate expression but how do you repress or control it?\u201d&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">The road ahead<\/h2>\n\n\n\n<p>The Crocker lab continues to look deeply into the mechanisms that connect genotype and environment to phenotypes. In this, they are part of the growing field of phenomics \u2013 the systematic study of an organism\u2019s traits and how they vary and change during development as well as in response to the environment.<\/p>\n\n\n\n<p>\u201cI have worked at the interface of development and evolution almost my whole career,\u201d said Crocker. \u201cI think the question we are addressing in the lab is that of scale \u2013 from studying precise changes in the genome to the fitness of entire populations \u2013 we are working towards gaining an integrated understanding of the fundamental mechanisms behind the emergence of phenotypes.\u201d<\/p>\n\n\n\n<p>The studies also fit nicely with<a href=\"https:\/\/www.embl.org\/about\/programme\/\"> EMBL\u2019s 2022\u201326 Programme \u2018Molecules to Ecosystems\u2019<\/a> \u2013 an ambitious plan to study living systems in the context of their environments. \u200b\u200bPhenotypic evolution becomes particularly interesting in light of global concerns such as climate change, where many animals are under pressure to adapt quickly to fast-changing environments.<\/p>\n\n\n\n<p>\u201cThere\u2019s a lot more to learn,\u201d concluded Crocker. \u201cThere are many more nuances to phenotypes and layers and layers of information we still have to explore as a community.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL researchers are stepping outside the lab and thinking outside the box to understand the basic principles that underlie the development and evolution of organismal characteristics.<\/p>\n","protected":false},"author":124,"featured_media":56012,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2],"tags":[528,565,478,1704,665,552,31,833,43,1008,5740],"embl_taxonomy":[19191,18997],"class_list":["post-56006","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","tag-crocker","tag-developmental-biology","tag-drosophila","tag-embl-programme","tag-embryo","tag-enhancer","tag-evolution","tag-fruit-fly","tag-heidelberg","tag-mutation","tag-phenotype","embl_taxonomy-crocker-group","embl_taxonomy-justin-michael-crocker"],"acf":{"vf_locked":false,"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>EMBL researchers are expertly bridging natural and lab environments to understand the basic principles that underlie the development and evolution of organismal characteristics.<\/p>\n","related_links":[{"link_description":"Crocker group","link_url":"https:\/\/www.embl.org\/groups\/crocker\/"},{"link_description":"Developmental Biology unit","link_url":"https:\/\/www.embl.org\/research\/units\/developmental-biology\/"}],"source_article":[{"publication_title":"Developmental phenomics suggests that H3K4 monomethylation confers multi-level phenotypic robustness. ","publication_link":{"title":"","url":"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2211124722017247?via%3Dihub","target":""},"publication_authors":"Gandara L., Tsai A. et al.","publication_source":"Cell Reports","publication_date":"13 December 2022","publication_doi":"10.1016\/j.celrep.2022.111832"},{"publication_title":"Enhancer architecture and chromatin accessibility constrain phenotypic space during Drosophila development","publication_link":{"title":"","url":"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1534580722008474?via%3Dihub","target":""},"publication_authors":"Galupa R. et al.","publication_source":"Developmental Cell","publication_date":"9 January 2023","publication_doi":"10.1016\/j.devcel.2022.12.003"}],"in_this_article":false,"press_contact":"EMBL 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