{"id":3712,"date":"2015-09-25T11:03:45","date_gmt":"2015-09-25T10:03:45","guid":{"rendered":"https:\/\/blogs.ncl.ac.uk\/icamblog\/?p=3712"},"modified":"2015-09-25T11:10:03","modified_gmt":"2015-09-25T10:10:03","slug":"climbing-the-tree-of-life","status":"publish","type":"post","link":"https:\/\/blogs.ncl.ac.uk\/icamblog\/climbing-the-tree-of-life\/","title":{"rendered":"Climbing the Tree of Life"},"content":{"rendered":"<p><em><a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Martin.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\" size-full wp-image-3725 alignright\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Martin.jpg\" alt=\"Martin\" width=\"150\" height=\"113\" \/><\/a>In this week&#8217;s blog, <a href=\"http:\/\/www.ncl.ac.uk\/camb\/staff\/profile\/martin.embley\" target=\"_blank\">Professor Martin Embley<\/a> reflects on\u00a0the\u00a0 the journey that led to him, his collaborators and his laboratory to fundamentally change our views on evolution and the Tree of Life.<\/em><\/p>\n<p><strong>The Early Years<\/strong><\/p>\n<p>My early career was a bit of a random walk while I tried to figure out what I really wanted to do. After my PhD in Newcastle on bacterial diseases of trout and salmon, I got a job teaching industrial microbiology at North East London Polytechnic in 1984. It was an odd but interesting place, a number of staff appeared to have strong religious beliefs of various sorts and wanted to talk about them, and one colleague thought he could change traffic lights from red to green so he never had to slow down. I was keen to keep doing some research and I was interested in evolution, but like a lot of newly independent researchers I struggled to get any funding. My big break came when I got a \u201ccultural exchange\u201d grant from Newham Council to go to Poland to learn some molecular biology and I met Professor <strong>Erko Stackebrandt<\/strong> who was passing through. Erko had worked with <strong>Carl Woese<\/strong> in pioneering the use of ribosomal RNA sequences to investigate evolutionary relationships among prokaryotes. I persuaded him to let me visit his lab in Germany to learn the new techniques and in 1991 these skills got me a job at the Natural History Museum in London.<\/p>\n<p>The Museum wanted to set up a lab using molecular sequences to investigate evolutionary relationships. The film Jurassic park was just about to appear and there was tremendous excitement about the potential of ancient DNA. The Museum gave me free rein regarding my own research as long as\u00a0it had evolution at its core. So I decided<img loading=\"lazy\" decoding=\"async\" class=\"  wp-image-3723 alignright\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Tree-of-life.jpg\" alt=\"Tree of life\" width=\"242\" height=\"276\" \/> to work on the early evolution of eukaryotic cells. At the time two ideas were central to views of early eukaryotic evolution. One was that the \u201cthree domains tree of life\u201d was an accurate description of the relationships between eukaryotes and prokaryotes (you can see the tree <a href=\"http:\/\/www.pnas.org\/content\/87\/12\/4576.full.pdf\" target=\"_blank\">here<\/a>). The other was that some eukaryotes, including obligate intracellular <a href=\"https:\/\/en.wikipedia.org\/wiki\/Microsporidia\" target=\"_blank\">microsporidian<\/a> pathogens, had never had <a href=\"https:\/\/en.wikipedia.org\/wiki\/Mitochondrion\" target=\"_blank\">mitochondria<\/a> because they split from other eukaryotes before the mitochondrial endosymbiosis. I\u2019ve been trying to test these two ideas for the past 25 years and while it\u2019s often been difficult and frustrating, it has also been a lot of fun.<\/p>\n<p><strong>A Team Effort<\/strong><\/p>\n<p>Like most PI\u2019s I\u2019ve relied on attracting talented young scientists to do the work that we have published. <strong><a href=\"http:\/\/www.ncl.ac.uk\/camb\/staff\/profile\/robert.hirt\" target=\"_blank\">Robert Hirt<\/a><\/strong> walked into my lab off the street and asked me if he could do a project involving eukaryotic evolution and ecology. He already had a first author paper in Cell and now he wanted to do something different. We didn&#8217;t do much ecolog<img loading=\"lazy\" decoding=\"async\" class=\"  wp-image-3722 alignright\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria.jpg\" alt=\"Mitochondria\" width=\"267\" height=\"314\" srcset=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria.jpg 825w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria-255x300.jpg 255w\" sizes=\"auto, (max-width: 267px) 100vw, 267px\" \/>y together but Robert and I co-supervised PhD student <strong>Bryony Williams<\/strong> who showed that <a href=\"http:\/\/www.nature.com\/nature\/journal\/v418\/n6900\/full\/nature00949.html\" target=\"_blank\">microsporidians actually contained a tiny, hitherto overlooked mitochondrion, now often called a mitosome<\/a>.<\/p>\n<p>Unlike our own mitochondria, the microsporidian mitosome doesn\u2019t make <a href=\"https:\/\/en.wikipedia.org\/wiki\/ATP\" target=\"_blank\">ATP<\/a>, because it has lost all of the pathways used by classical mitochondria to make energy. <strong>Alina Goldberg<\/strong> in our lab \u2013 now at Newcastle &#8211; and <strong>Sabine Molik<\/strong> in the lab of <strong>Roland Lill<\/strong> in Germany spent <a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria-2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"  wp-image-3721 alignleft\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria-2.jpg\" alt=\"Mitochondria 2\" width=\"284\" height=\"303\" srcset=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria-2.jpg 825w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Mitochondria-2-281x300.jpg 281w\" sizes=\"auto, (max-width: 284px) 100vw, 284px\" \/><\/a>the next seven years showing that the <a href=\"http:\/\/www.nature.com\/nature\/journal\/v452\/n7187\/full\/nature06606.html\" target=\"_blank\">mitosome functions in the biosynthesis of essential cytosolic and nuclear Iron\/Sulphur (Fe\/S) proteins<\/a>.\u00a0The discovery of a tiny mitochondrion in microsporidia (Figures 1 and 2) was an important piece of evidence that led to current ideas that the mitochondrial endosymbiosis occurred at the origin of eukaryotes. Thus, it is now <a href=\"http:\/\/www.nature.com\/nature\/journal\/v440\/n7084\/abs\/nature04546.html\" target=\"_blank\">thought<\/a> that all eukaryotes contain an organelle related to mitochondria, and its most conserved function is in <a href=\"https:\/\/en.wikipedia.org\/wiki\/Iron-sulfur_protein\" target=\"_blank\">Fe\/S protein<\/a> biogenesis, not ATP production.<\/p>\n<p><strong><a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-large wp-image-3718\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1-1024x622.jpg\" alt=\"Figure 1\" width=\"584\" height=\"355\" srcset=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1-1024x622.jpg 1024w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1-300x182.jpg 300w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1-494x300.jpg 494w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-1.jpg 1320w\" sizes=\"auto, (max-width: 584px) 100vw, 584px\" \/><\/a><a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-large wp-image-3719\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2-1024x537.jpg\" alt=\"Figure 2\" width=\"584\" height=\"306\" srcset=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2-1024x537.jpg 1024w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2-300x157.jpg 300w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2-500x262.jpg 500w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-2.jpg 1412w\" sizes=\"auto, (max-width: 584px) 100vw, 584px\" \/><\/a>Competing Hypotheses<\/strong><\/p>\n<p>In the three domains tree of life, <a href=\"https:\/\/en.wikipedia.org\/wiki\/Eukaryote\" target=\"_blank\">eukaryotes<\/a> are a separate domain that is most closely related to the domain <a href=\"https:\/\/en.wikipedia.org\/wiki\/Archaea\" target=\"_blank\">Archaea<\/a> and the host for the mitochondrial endosymbiont is already a eukaryote. Although this hypothesis appears in most textbooks, there have actually been a number of alternative hypotheses published over the years (Figure 3 shows one of them), but these have largely been ignored. <strong>Cymon Cox<\/strong> spent three years analysing molecular sequence data to identify which of the competing published hypotheses was best supported and reached the surprising conclusion that it was not the three domains tree but an alternative hypothesis called the <a href=\"https:\/\/en.wikipedia.org\/wiki\/Eocyte_hypothesis\" target=\"_blank\">eocyte tree<\/a> (you can read a discussion about the differences between the two trees including a picture of the eocyte tree <a href=\"http:\/\/phenomena.nationalgeographic.com\/2012\/12\/20\/redrawing-the-tree-of-life\/\" target=\"_blank\">here<\/a>). In the eocyte tree, eukaryotes originate from <em>within<\/em> the Archaea, suggesting that eukaryotes are not a primary domain of life like Archaea and Bacteria, but are instead a product of genetic and cellular contributions from both prokaryote domains. Very excited by these results, we sent Cymon\u2019s paper to Nature where it was reviewed and quickly rejected. We appealed, it was revised, it was reviewed again, and it was rejected again, all in all pretty dispiriting, but a common experience for most scientists. However, after hearing me talk about Cymon\u2019s work at a meeting, we were invited to submit Cymon\u2019s paper to PNAS where it was <a href=\"http:\/\/www.pnas.org\/content\/105\/51\/20356.full\" target=\"_blank\">finally published in 2008<\/a>.<\/p>\n<p><strong><a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-large wp-image-3720\" src=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3-1024x489.jpg\" alt=\"Figure 3\" width=\"584\" height=\"279\" srcset=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3-1024x489.jpg 1024w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3-300x143.jpg 300w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3-500x239.jpg 500w, https:\/\/blogs.ncl.ac.uk\/icamblog\/files\/2015\/09\/Figure-3.jpg 1508w\" sizes=\"auto, (max-width: 584px) 100vw, 584px\" \/><\/a>A Mixed Response<\/strong><\/p>\n<p>Although Cymon\u2019s paper has been highly cited it is true to say that the initial response from the community was very mixed. We received emails suggesting that we had manipulated our results to get the answer we wanted and one of the reviewers told us that it was impossible to infer such ancient events using molecular sequences. In responding we agreed that it was difficult to be confident about anything that happened billions of years ago based upon small amounts of data and even the best methods of analysis, but that people in the field seemed happy to use the same data and worse methods to support the three domains tree. Cymon eventually moved on, scarred but not defeated, and <strong>Tom Williams<\/strong> took over the project when he came to Newcastle on a Marie Curie Fellowship in late 2010. Over the next few years, more data was published as new Archaea were discovered and new methods of analysis were developed, and every analysis that Tom, or others, did on these data produced a version of the eocyte tree, so that it is now the best supported hypothesis &#8211; <a href=\"http:\/\/www.nature.com\/nature\/journal\/v504\/n7479\/full\/nature12779.html\" target=\"_blank\">at least in our opinion<\/a>.<\/p>\n<p><strong>More evidence emerges<\/strong><\/p>\n<p>Hypotheses are only useful when they make predictions that can be tested by further research, and evolutionary hypotheses are no different. The eocyte tree predicts that new species that share more features in common with eukaryotes will be discovered among the Archaea, and this prediction now appears to have been spectacularly fulfilled by <a href=\"http:\/\/www.nature.com\/nature\/journal\/v521\/n7551\/abs\/nature14447.html\" target=\"_blank\">recent discoveries<\/a> from <strong>Thijs Ettema<\/strong>\u2019s lab in Sweden.\u00a0The new paper describes the discovery, so far only from <a href=\"https:\/\/en.wikipedia.org\/wiki\/Metagenomics\" target=\"_blank\">metagenome<\/a> data, of an archaeal lineage called <a href=\"https:\/\/en.wikipedia.org\/wiki\/Lokiarchaeota\" target=\"_blank\">Lokiarchaeota<\/a> that contains many genes for proteins that were previously thought to be eukaryotic specific, including homologues of proteins used in the <a href=\"https:\/\/en.wikipedia.org\/wiki\/Cytoskeleton\" target=\"_blank\">eukaryotic cytoskeleton<\/a>, in <a href=\"http:\/\/www.nih.gov\/news\/health\/apr2013\/nichd-30.htm\" target=\"_blank\">membrane remodeling<\/a> and in <a href=\"https:\/\/en.wikipedia.org\/wiki\/Phagocytosis\" target=\"_blank\">phagocytosis<\/a>. \u00a0This is incredibly exciting and the challenge is now to isolate Lokiarchaeota and other new lineages into culture so that their biology and physiology can be studied in the laboratory.<\/p>\n<p><strong>An Interesting Journey<\/strong><\/p>\n<p>Scientific work is often written up as if it were a linear progression towards improved understanding, a type of \u201c<a href=\"https:\/\/en.wikipedia.org\/wiki\/Whig_history\" target=\"_blank\">Whig history<\/a>\u201d which does not accurately reflect how science is really done. In reality, science is a collaborative endeavour with lots of dead ends, confusion and false trails, and we could easily be walking down some of those still. Nevertheless, the currently prevailing paradigm for eukaryotic evolution is now very different to the popular views held in the 1990s when I started my research career. All eukaryotes are now thought to contain a mitochondrial homologue that generally functions in Fe\/S protein biogenesis, and the host for the mitochondrial endosymbiont is thought to have originated from within the Archaea. Eukaryotes are thus viewed as the product of an interaction between (at least) those two prokaryotic partners and are not a primary domain of life but one derived from prokaryotic antecedents. The complex features that we take to define eukaryotic cells including our own, such as the nucleus, large genomes and diversity of RNAs, are thus secondary features that have evolved since those primordial interactions. I\u2019m not sure what my religious former colleagues would have made of the work I\u2019ve done since leaving NELP, but it\u2019s been an enjoyable and interesting journey for me.<\/p>\n<p><em>Links<\/em><\/p>\n<p>The Tree of Life:\u00a0<a href=\"http:\/\/www.pnas.org\/content\/87\/12\/4576.full.pdf\" target=\"_blank\">http:\/\/www.pnas.org\/content\/87\/12\/4576.full.pdf<\/a><\/p>\n<p>Bryony Williams&#8217; paper:\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v418\/n6900\/full\/nature00949.html\" target=\"_blank\">http:\/\/www.nature.com\/nature\/journal\/v418\/n6900\/full\/nature00949.html<\/a><\/p>\n<p>Alina Goldberg and Saline Molik paper:\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v452\/n7187\/full\/nature06606.html\" target=\"_blank\">http:\/\/www.nature.com\/nature\/journal\/v452\/n7187\/full\/nature06606.html<\/a><\/p>\n<p>Mitochondria and Fe\/S proteins:\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v440\/n7084\/abs\/nature04546.html\" target=\"_blank\">http:\/\/www.nature.com\/nature\/journal\/v440\/n7084\/abs\/nature04546.html<\/a><\/p>\n<p>The eocyte tree:\u00a0<a href=\"http:\/\/phenomena.nationalgeographic.com\/2012\/12\/20\/redrawing-the-tree-of-life\/\" target=\"_blank\">http:\/\/phenomena.nationalgeographic.com\/2012\/12\/20\/redrawing-the-tree-of-life\/<\/a><\/p>\n<p>Cymon Cox paper:\u00a0<a href=\"http:\/\/www.pnas.org\/content\/105\/51\/20356.full\" target=\"_blank\">http:\/\/www.pnas.org\/content\/105\/51\/20356.full<\/a><\/p>\n<p>Tom WIlliams paper:\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v504\/n7479\/full\/nature12779.html\" target=\"_blank\">http:\/\/www.nature.com\/nature\/journal\/v504\/n7479\/full\/nature12779.html<\/a><\/p>\n<p>Thijs Ettema lab paper:\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/v521\/n7551\/abs\/nature14447.html\" target=\"_blank\">http:\/\/www.nature.com\/nature\/journal\/v521\/n7551\/abs\/nature14447.html<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>In this week&#8217;s blog, Professor Martin Embley reflects on\u00a0the\u00a0 the journey that led to him, his collaborators and his laboratory to fundamentally change our views on evolution and the Tree of Life. The Early Years My early career was a &hellip; <a href=\"https:\/\/blogs.ncl.ac.uk\/icamblog\/climbing-the-tree-of-life\/\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1713,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[137,139,60,138,22,86],"class_list":["post-3712","post","type-post","status-publish","format-standard","hentry","category-general","tag-archea","tag-eocyte-tree","tag-icamb-2","tag-microsporidian","tag-mitochondria","tag-tree-of-life"],"_links":{"self":[{"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/posts\/3712","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/users\/1713"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/comments?post=3712"}],"version-history":[{"count":15,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/posts\/3712\/revisions"}],"predecessor-version":[{"id":3737,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/posts\/3712\/revisions\/3737"}],"wp:attachment":[{"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/media?parent=3712"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/categories?post=3712"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.ncl.ac.uk\/icamblog\/wp-json\/wp\/v2\/tags?post=3712"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}