Essä om genredigering och demokrati

http://sverigesradio.se/sida/avsnitt/976110?programid=503

Människan har nu slutligen makt över både miljö och arv. Vad kommer hon att göra när hon kan välja sin egen genuppsättning? Essä om CRISPR och demokrati i Obs i P1.

För de som är intresserade av ämnet, rekommenderas boken A Crack in Creation (på svenska Sprickan i skapelsen) av en av teknikens skapare Jennifer Doudna.

Kort recension:

”Sprickan i skapelsen” är Jennifer Doudnas (och hennes medförfattare Samuel Sternbergs) bidrag till avmystifieringen av CRISPR. Doudna var tillsammans med bland annat den före detta Umeå-forskaren Emmanuelle Charpentier huvudpersoner i upptäckten av CRISPR-fenomenet, så det går knappast att få ämnet sammanfattat av en creddigare person. Hon nämner upprepade gånger att hon anser det vara sitt ansvar att föra ut debatten om genredigering till allmänheten och det finns ingen anledning till att tvivla på hennes intentioner. I boken dyker författarna in och ut ur vetenskapliga detaljer med stor finess och lättförklarliga illustrationer utan att för den skulle frångå den större helhetsbilden av vad alla forskningsresultat innebär. De täcker både genterapins historia, CRISPRs upptäckt (i grundforskning inom bakteriers immunförsvar), de myriader av tillämpningar av tekniken som utvecklats de senaste åren och de moraliska problem som det ställer oss inför. Doudna och Sternberg ger således läsarna en koncis och bra sammanfattning av dåtid, nutid och framtid som bildar en utmärkt utgångspunkt för diskussioner.

Boken är naturligtvis inte felfri. Den innehåller många onödiga självbiografiska inslag om Doudnas tidiga forskningskarriär, labbkonferenser på exotiska platser och möten med framstående politiker. Hon faller emellanåt in i en bilförsäljaremodus när hon berättar hur nästintill alla världens problem kan lösas med CRISPR. Den infekterade patentbråk om CRISPR-teknologin – som hon är en del av och som just nu pågår i flera stater i USA – nämns inte med ett ord. Istället ligger konflikten som en surrande underton i hela boken och Doudna tar i överkant när hon i detalj beskriver att hennes artiklar var först med att utstaka vägen för CRISPR-tillämpning. Men bortser man från dessa svagheter finns det i dagsläget ingen förklarande text om CRISPR för lekmän som kommer i närheten av att vara lika bra som ”Sprickan i skapelsen”.

Annonser

A Colony

colony

The line between uni- and multicellular organisms is not straight forward. These cells, numbering in the billions, originate from a single unit. They are, at this stage, most probably differentiated. They are most certainly communicating chemically. Maybe bioelectrically as well. They are united in their survival strategy in something that resembles altruistic behavior. They are not cannibalizing off of each other. They are not inhibiting each other’s growth in antagonistic ways. On the contrary, in certain aspects, these billions of cells are working in perfect concert.

Are they just a pile of unicellular bacteria, restricted in space from dissemination, evolving at their individual pace? Or are they a singular, coherent unit – united against the outside world in their struggle for survival?

They are, I would argue, both.

Vilken sorts forskning selekterar anslagsgivare för?

Blev inbjuden att skriva en åsiktstext om forskning- och innovationspolicyn/politik i tidningen Entré. Ni hittar texten här:

http://www.esbri.se/artikel_visa.asp?id=1884

 

Fisksamhällen, människosamhällen och Machiavelli

Skrev en ny essä till Obs i december om hur Nobelpriset i ekonomi kunde länkas till forskning kring fiskbeteende. Igen, jag är verkligen sämst på att läsa in texter. Förmodligen lättare att läsa än att lyssna på essän.

http://sverigesradio.se/sida/avsnitt/828903?programid=503


 

När astronauten Alan Shepard, i egenskap av den första amerikan att åka till rymden, ombads kommentera resan ska han ha skämtsamt sagt att ”det är en väldigt tillnyktrande känsla att befinna sig i rymden och inse att kvalitén på ens säkerhet bestäms av lägsta-budet i en statlig upphandling” (1).

Det citatet fångar träffande kärnan i de intressekonflikter som uppstår mellan olika parter i ett projekt. I det här fallet mellan den resande astronauten – med endast lite plåt mellan sig och det allslukande vakuumet – och den statliga finansiären.

Säkerhet kontra kostnad. Risk kontra besparingar.

I år tilldelades Bengt Holmström och Oliver Hart Sveriges Riksbanks pris i ekonomisk vetenskap till Alfred Nobels minne för sina bidrag till kontraktteori – ett forskningsfält inom vilket man försöker reda ut hur man bäst hanterar intressekonflikter med hjälp av – just det – kontrakt.

Hur belönar man en anställd med många arbetsuppgifter varav endast några går att mäta? Man frikopplar lönen från prestation så att hen inte bara koncentrerar sig på de mätbara uppgifterna. Hur utformar man bäst ett långsiktigt kontrakt, när det är omöjligt att förutse hur världen kommer se ut om några år? Man tilldelar beslutsrätten till den part med störst anledning att vidta åtgärder om saker skiter sig. Och så vidare (2).

Intressekonflikter, incitament, marknadskrafter – dessa saker präglar våra beteenden. Om de ter sig intuitiva för dig, så får jag lov att gratulera; du är allmänmänsklig. Kungliga Vetenskapsakademien summerar nämligen sin populärvetenskapliga information om priset med att ”årets pristagare har hjälpt oss förstå många av de kontrakt vi observerar i verkligheten” (2).

Nyckelordet är ”observerar”, dvs att ekonomerna har utvecklat ett teoretiskt ramverk som förklarar det vi redan ser. Vi vet redan att människan sedan urminnes tider hittat på sätt att reglera intressekonflikter, incitament och marknadskrafter. De egenskaper som behövs, och som vi människor har, för att hantera dessa fenomen, beskrivs av vissa evolutionspsykologer med termen ”Machiavellisk intelligens” – så kallad efter den listiga florentinska politiska filosofen Niccolo Machiavelli.

Akademiker har länge sökt svaret på varför högre primater utvecklat så oproportionerligt stora hjärnor jämfört med andra organismer. En stor hjärna är nämligen inte särskild praktisk. Hjärnan suger upp mycket energi, är kostsam att utveckla & underhålla och dessutom känslig för skador. Viktigast av allt: en så stor och kognitivt stark hjärna är knappast nödvändig för en framgångsrik tillvaro och fortplantning. Om du inte tror mig, fråga reptilerna.

Hypotesen om den sociala hjärnan, med ett visst sinne för dramatik även alltså kallad hypotesen om Machiavellisk intelligens, hävdar att social konkurrens om reproduktion genom årtusenden har drivit fram stora hjärnor hos högre primater (3).

Den påstår alltså att en stor hjärna med mycket kognitiv kraft behövs för att få bra social förståelse inom ett komplext nätverk, som till exempel en flock. Den ger förmågan att orientera sig i förhållande till konkurrenter och anförvanter och en talang för politiska intriger. Detta i sin tur leder till reproduktionsframgång. Innegänget får ligga, kan man sammanfatta det som.

Ett exempel som ofta lyfts fram till stöd för hypotesen om den sociala hjärnan är schimpanssamhällen där det inte nödvändigtvis är den starkaste eller mest våldsamma schimpansen som blir alfahane, utan den som knyter de mesta och bästa politiska banden till andra flockmedlemmar (4).

En annan intressant aspekt av teorin gör gällande att det mänskliga språket rent av är sprunget ur behovet av att skvallra. Skvaller har enligt teorin evolutionära syften: exempelvis kommunicerar man varningar till varandra om opålitliga samarbetspartners, stärker banden inom den skvallrande gruppen osv. Skvaller är en av de grundläggande sakerna som gör oss mänskliga (4).

Forskning om Machiavellisk intelligens försöker alltså beskriva de evolutionära processer som leder fram till förmågan att analysera intressekonflikter, incitament, för- och nackdelar med samarbete. Dvs samma fenomen som kontraktteorin beskriver ekonomiskt. I den bemärkelsen kan man kalla kontraktteori för Praktisk Machiavellisk Beteendevetenskap. Den tillåter oss att outsourca kognitionskrävande processer till färdiga formler.

Men evolutionspsykologin är inte ett alldeles okontroversiellt fält och har både sina försvarare och belackare. Till exempel har allt mer bevis hopats under senare år som omkullkastar kopplingen mellan hjärnstorlek och Machiavelliskt beteende. Och framförallt har dessa fynd gjorts under havsytan.

Sedan ca 15-20 år tillbaka har beteendevetare frångått fastlåsningen vid primatforskning och börjat studera andra djur allt mer. En av de mest framgångsrika forskarna, Redouan Bshary, har riktat in sig på att studera marknadskrafter inom fisksamhällen (5). Och det han har hittat är utomordentligt uppseendeväckande.

I vissa korallrev finns ett system där putsarfiskar hjälper så kallade klientfiskar att bli kvitt sina parasiter. Klientfiskarna uppsöker stationer med putsarfiskar som äter upp parasiterna från klientfiskarnas fjäll. Putsarfiskarna får mat och klientfiskarna blir friskare.

Men. Putsarfiskarna föredrar egentligen att ta en tugga av den näringsrika slemhinnan på klientfiskarnas kroppar- något som gör ont, räknas som fusk och leder till konflikt mellan parterna.

Bsharys forskningsgrupp upptäckte i snabb takt följande saker i detta system. När det fanns putsarfiskar på plats fuskade putsarfiskarna mer. Det vill säga att marknadskrafter som tillgång och efterfråga gällde och för tillfället rådde säljarens marknad. Om däremot ett gäng klientfiskar iakttog putsningen, fuskades det mindre. Putsarfisken hade då incitament att inte skrämma bort eventuella klienter. Det är viktigt att ha ett gott rykte! Fuskades det alldeles för mycket straffade klientfiskarna kontraktsbrytarna genom att bojkotta eller jaga putsarfiskarna, som då slutade fuska. Forskarna observerade till och med något som liknade en blidkande gest vid dålig service: en försonande fenmassage över klientfiskarnas ryggar när de blev arga (5).

När beteendevetarna försökte korrelera hjärnstorleken mellan fiskar som var kapabla respektive inkapabla till denna form av Machiavellisk beteende såg de inga starka samband (6). Vad de däremot observerade var att i vissa glesbefolkade fisksamhällen, med mycket lägre social komplexitet, var putsarfiskarna betydligt mindre listiga (5). Det vill säga att Machiavellisk beteende inte är kognitivt krävande, men något som utvecklas på annat vis i socialt komplexa system.

Man ska vara försiktig med att extrapolera zoologiska kunskaper till människan, men tankarna söker sig dit ändå: kan man tillämpa dessa observationer på kontraktteorin? Är människor i glesbygden mindre Machiavelliskt lagda än människor i miljonstäder? Kan lägsta-budet på en statlig upphandling för en rymdkapsel vara av olika kvalité beroende på den sociala komplexiteten i avsändarens miljö? Borde det isåfall ha varit det som oroade astronauten Alan Shepard? Det är inte omöjligt att svaren på en del ekonomiska frågeställningar finns i sjön.

 

 

 

Referenser

  1. New Mexico Museum of Space History http://www.nmspacemuseum.org/halloffame/detail.php?id=55

 

  1. Nobelprize.org

https://www.nobelprize.org/nobel_prizes/economic-sciences/laureates/2016/popular-economicsciences2016-sv.pdf

 

  1. Dunbar & Shultz. Evolution in the Social Brain, 2007. Science.

 

  1. Harari. Sapiens – En kort historik över mänskligheten, 2015. Natur & Kultur Allmänlitteratur

 

  1. Abbot. Animal behaviour: Inside the cunning, caring and greedy minds of fish, 2015. Nature.

 

  1. Chojnacka et al. Relative Brain and Brain Part Sizes Provide Only Limited Evidence that Machiavellian Behaviour in Cleaner Wrasse Is Cognitively Demanding, 2015. PLoS One

Recension av ny Humboldt-biografi i Sydsvenskan

Jag recenserade nyligen ”Alexander von Humboldt – Vetenskapens bortglömde hjälte” av Andrea Wulf i Sydsvenskan 9/10-16.

http://www.sydsvenskan.se/2016-10-09/en-annan-sorts-hjalte

The Lucy of Microbiology – The Relationship between Organisms and the Origins of us Eukaryotes

Due to what appears to be a recent (and, honestly surprising) interest in this post from non-Swedish visitors, I translated the originally Swedish text to English. Enjoy, non-Swedes.

 

 

 

There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one […]

– Charles Darwin, On the Origins of Species, 1859.

 

People didn’t understand the size of my contributions. They had no appreciation for what not having a microbial phylogeny meant, and therefore no appreciation for what having one would mean.”

– Carl Woese, intervju i Science, 1997.

 

”[The Norse deity] Loki has been described as ‘‘a staggeringly complex, confusing, and ambivalent figure who has been the catalyst of countless unresolved scholarly controversies’’, in analogy to the ongoing debates on the origin of eukaryotes”

– Spang et al., Nature, 2015.

 

 

 

Last spring, a research team lead by Thijs Ettema at Uppsala University, Sweden, published one of the greatest scientific discoveries of 2015 (1). Regrettably, their work did not garner much media attention in Sweden. This could potentially be explained by the fact that, in general, breakthroughs in evolutionary sciences are not considered to be as sexy as breakthroughs in fields such as medicine or technology. Potentially, some background knowledge could be of use in order to appreciate the significance of their findings.

 

All life on our planet is sprung from a single source. We have extremely strong molecular evidence that point to this fact, which I’ll come to in a moment. Bearing this mind, researchers have tried to map the relatedness of species ever since the revolutionary work of Darwin revealed that all forms of life is related to all other forms of life on Earth. The biological sciences are fantastic in many ways – especially for a scientist, I shamelessly might add – with one particularly pleasing aspect being their ability to predict the discoveries that will occur in the future should the hypothesis supported by the current data withstand. This is of course not unique to biological sciences; Higgs predicted the particle that was named after him some 50 odd years before it was discovered. Mendeleev, while constructing the periodic table, predicted the existence of eight thus far unknown elements (and even the geographical locations where they could be found) many years before they were discovered. There are many more examples.

 

But biology is different because, in essence, we are dealing with life. And life, of course, is dynamic and interchangeable. In particular, a biologist has to deal with time in a manner that sets him/her apart from a physicist or chemist. This is particularly true for evolutionary scientists. Time might render species, and the information they carry within them, extinct, decidedly preventing any modern researcher from studying, analyzing, categorizing or mapping them. Moreover, the internal complexity of, lets say, a cell, might cause a dizzying map of interactions difficult to base predictions off of (despite these roadblocks, Monod and Jacob predicted the central mechanisms of gene regulation with an almost eerie accuracy before they discovered the actual molecular factors that physically carried out the processes) (2).

 

Due to these complexities, it is all the more enjoyable when discoveries predicted by our current understanding of biology are made.

 

From Darwin to Haeckel – the emergence of the phylogenetic sciences

First, a little historical background (I would not be me if I did not drag history in it, would I?). As soon as Darwin had formulated his theory of evolution, he foresaw that all life on earth probably had one (or a few) origin(s) (3) – he even ventured to guess that it originated somewhere in ”a warm little pond” (4). Soon after, researchers began to more closely study the relationships between organisms.

 

How did one go about investigating these issues at the time? For lack of better methods, they used the morphology of organisms – basically, studying and comparing how different species looked. The idea was that organisms that looked alike and had similar physiology should be reasonably close-related. Ernst Haeckel, a controversial biologist who later came to be one of the chief proponents of eugenics and racial hygiene in Germany (5), was a pioneer in the studies of the kinship and origin of species and the first to introduce the term phylogeny for this purpose. Haeckel was an interesting figure in many regards. He developed at least three scientific theories that made a splash upon launch, but of which all three were completely false. These included the recapitulation theory (the details of which are not important to dwell on in the current context), the human racial hierarchy (where he put the white Europeans, ”Homo Mediterraneus”, on top, being that he was a rampant racist) and that that man originates from Asia (DNA evidence clearly shows that man originates from Africa, something that Darwin also predicted). Despite his huge scientific blunders (not to mention his repugnant racial values), Haeckel managed to make some long-lasting contributions to science. Among other things, he mapped thousands of new species, established developmental biology as a new scientific field, and constructed the first phylogenetic tree based on the morphology of species. His division of life on Earth into three major kingdoms – multicellular plants (plantae), multicellular animals (animalia) and unicellular organisms (protista) – withstood for a very long time. Thus, the proverbial ball of mapping life’s kinship was rolling.

 

Haeckel_arbol_bn-1

The phylogenetic tree from Haeckel’s ”Generelle Morphologie der Organism” (1866) where life is divided into the three branches ”plantae”, ”protista” and ”animalia”.

 

 

 

 

But establishing the relationship of species by virtue of their morphology alone soon proved to be scientifically inadequate. Not least, a phenomenon known as convergent evolution throws a monkey wrench into any accurate systematization and catalogization. Convergent evolution describes a process in which species develop similar physical features in parallel with, but separate from, one another. To exemplify, we today know that the hippopotamus is more closely related to dolphins than to elephants. Dolphins are enormously more closely related to the hippopotamus than to sharks, and so on and so forth. These relationship patterns can be difficult to derive from strictly morphological studies (6).

 

Thus, as researchers obtained more advanced biochemical methods, morphology studies were abandoned in favor of biochemical analyses. For instance, during the 1930s and stretching a few decades forward, the reactivity of the immune system of various animals to the tissues of other animals was used to establish relative relationships – the less the immune system reacted to the foreign tissue, the more close the relationship (7). This may sound crazy, but it’s quite cunning. Due to organisms being decidedly more biochemically than morphologically similar to close relatives, methods such as the mentioned ”systematic serology” improved the resolution of phylogenetic studies (at least for animals with immune system).

 

But the real breakthrough came with molecular biology.

 

 

A nuclear discovery

Before going any further, we must make a brief cell biological detour for the sake of the understandability of the rest of the story. When the electron microscope was invented, and man was able to visualize life at the subcellular level for the very first time, a fundamental discovery was made with regard to the distinction between different forms of life. It was observed that certain cells – those from animals, plants, amoebas, etc. – have something called a cell nucleus, a compartment in which the cellular DNA was collected and protected in a shell. Other cells – bacterial cells – lack the nucleus, meaning that the DNA is freely distributed inside the entire cell. These different cell types were thus categorized into ”eukaryotes” (those with a nucleus) and ”prokaryotes” (ie, before the cell nucleus or absence of cell nucleus). It was immediately clear that a very important evolutionary step separated these two groups, a notion that was further pointed to by the fact that, in addition to the nucleus, prokaryotes lack many other organelles (specialized cellular apparatuses that perform specific cellular processes). If you imagine the eukaryotic cell as being an iPhone, then the prokaryotic cell is like that old Nokia with the snake game. It is seemingly less complex, has no camera nor a color display. Even though they are both fundamentally phones, there’s a big difference in the observed level of complexity.

 

When scientists realized these fundamental differences, a new branch of the phylogenetic tree was allocated specifically to prokaryotes, called monera, to complement the existing animalia, plantae and protista (which now became the branch of unicellular eukaryotic microorganisms including amoebas). Prokaryotes were from then on more or less synonymous with ”bacteria”. But that all changed in the late 1970s when a physicist named Carl Woese became interested in the origins of life.

 

image002

A schematic comparison of a prokaryotic and eukaryotic cell. Take note of the cell nucleus and the more advanced cellular architecture of the eukaryotic cell.

 

 

Carl Woese –The ignored mastermind oddball

The time at which Woese entered the scene, scientists had unsuccessfully been trying to phylogenetically categorize bacterial species for decades. But seeing that these studies were based on bacterial morphology and metabolism (basically what substances a bacterium could eat) – something that differs considerably, even between closely related bacteria – they soon gave up (8). One of the giants of the field, Roger Stanier, went so far as to say ”the ultimate scientific goal of biological classification cannot be achieved in the case of bacteria.” An astonishing statement! Bacterial species were simply too diverse and interchangeable for scientists to be able to subdivide them into classes and families as had been done with animals and plants.

 

But this notion only held water if one restricted one’s analyses to morphology and metabolism studies. The eminent Carl Woese was much more farsighted than that. During the 1970s, he developed an entirely new approach to study the relatedness of species – an approach that is omnipresent in the modern biology today.

 

As Weose was formally trained in physics and biophysics, his tactic differed from that of other, more classically trained, microbiologists. The theoretical basis for his method was that certain genes are found in all organisms. For example, all cells replicate their DNA. All cells must be able to produce proteins. The molecular mechanisms of these processes are almost identical in all kinds of cells, meaning that the same processes (with some modifications) take place in a soil bacterium, an amoeba, a jellyfish, a fern, a chicken and a human with respect to the central cellular mechanisms. Genes that are involved in these vital processes must by nature thus be ”stable”. This means that the enzymatic activity – the function – of the gene product is so central to the survival of the cell, that it cannot afford too many mutations (changes) in these genes (due to the fact that mutations can wreck their functions).

 

Woese idea was theoretically simple and sound. He figured that if one studies the sequences of said genes, and distinguishes the occasional mutations that nonetheless have occurred over time (without affecting the function too much), one could theoretically trace back the origin of the gene, and thus the origin of the species carrying it. That is, if ”Gene X” (found in all organisms) has two mutations in the locations 16 and 418 in ”species Y”, but two mutations in the locations 16 and 377 in ”species Z”, they have a common origin in which the mutation 16 was included, but had later evolved in different directions and accumulated mutations 418 and 377 seperately from one another. By looking at the same gene in many different species, one can thus mathematically devise a phylogenetic tree. Given that mutations occur at a specific rate, meaning the existence of a proverbial “genetic clock” that introduces (for the sake of argument, let’s say,) one mutation every 100 000th generation in these genes, one could also calculate when species last shared a common ancestor.

 

But, if the theory was simple, the method available at the time for investigating gene sequences certainly wasn’t. It was called ”oligonucleotide cataloging”, and the bench work was laborious and monotonous. Woese worked alone. He devoted himself for 10 years to classify bacterial species by cataloging their so-called ribosomal RNA (rRNA). While doing this, he developed a reputation for being an oddball, a half-crazed scientist who surrounded himself with thousands of oligonucleotide sequencing films that he used to deduce specific rRNA sequences in solitude for days on end (8).

 

Then one day in 1976, one of the magic moments of science happened. A colleague of Woese’s approached him to ask if he could take a look at the phylogeny of a peculiar type of methane-producing bacterium that he studied. Woese agreed to do it. However, when he saw the ribosomal sequences, he became confounded. Woese thought he had made a mistake during the experimentation, so he repeated it. But the results were again the same. He went to his colleague, shook his head and said ”these things aren’t even bacteria” (8). The colleague calmly reassured Woese ”Carl, it looks like a bacteria, it is a prokaryote, it behaves like a bacteria” and so on. But Woese, who had conducted hundreds of such analyzes, was adamant. These were unlike any other previously studied prokaryote or eukaryote. These were no bacteria.

 

These were something else.

 

 

Archaea – the neglected life form that gave rise to us

Woeses revolutionary, now classic, work was published in 1977 (9). The molecular data showed that the tree of life does not consist of the previously proposed branches based on morphology. Instead, the species fell into one of three domains; bacteria, archaea (which also were prokaryotic, and the organisms Woese had been given by his colleague) and eukarya (which was a sister branch of archaea and therefore shared a common origin). All three branches have a common root, ie one origin of life, which Woese thought was closest the archaea branch (hence the name, from “archaic”). As a science journalist put it, the claim that archaea formed one of only three separate and equal branches of life was perceived to be as bizarre as if ”a colony of aliens creatures had suddenly been discovered living secretly in the backyard of suburbia” (8). How had everyone missed one-third of the life on earth for all these years? Woese findings were met by a huge skepticism. For a while, he was practically ostracized from the scientific community. Many microbiologists simply chose to ignore him and his work.

 

800px-Phylogenetic_tree.svg

The phylogenetic tree based on the work of Carl Woese. Notice how small the actual genetic difference is between animals and plants compared to the rest of the life on Earth.

 

But with time, Woese was vindicated. After a few years of investigations by other research groups (mostly German), more and more evidence piled up in support of Woese’s theory (10). Archaeal species were often found to be extremophiles, that is, they live in extreme environments such as hot water springs, extremely saline environments, etc. They differ from bacteria with respect to, for instance, their cell wall and RNA polymerase (a key molecule in the cell gene-expression machinery). They differ obviously from eukarya seeing that they are much less cellularly complex, no nucleus etc. But despite archaea being prokaryotic, they have several factors in common with eukaryotes that bacteria do not, such as similar RNA- and DNA-polymerases (10). Woese was subsequently the recipient of several prestigious awards and grants (8). But the time of ostracism had left its mark and Woese remained bitter about the initial lack of appreciation for his research and the blacklisting he experienced in the late 70’s (8). He never got over it until he passed in 2012.

 

The phylogenetic tree proposed by Woese is in fact still controversial in some circles. Some claim that the phylogenic relationships are still not fully investigated to support a separate branch for archaea (10). Others simply refuse to accept it. Others yet discuss whether eukaryotes evolved from archaea, or if these domains simply have a hitherto unknown common cellular ancestor. The evidence seems to point toward the former hypothesis (1). This would mean that, if you, the reader, follow your genealogy far enough back in time you will reach an archaea :).

 

But in analogy with archaeologists that search for fossils that show the intermediate steps between ancient apes and the modern man, microbiologists have been long searching for the species that bridge the gap between the prokaryotic and eukaryotic branches of the tree of life. Phylogeny predicts that such a species should exist, but we have not found it. Maybe it has gone extinct? The evolutionary ”jump” between the prokaryotic and eukaryotic cell – the great complexity that ”suddenly” appears in eukaryotes – has simply been too big for us to be able to map the direct relationship between these domains. It’s as if archeologists would not have found Lucy, or Homo habilis or H. eructus. We are missing some key species in the transition phase from prokaryotic to eukaryotic life.

 

Namnlös

A large gap existed between known archaea and known eukaryotes. Notice the distance between the diplomonads and archaea branch.

 

 

At least that was the case until Thijs Ettemas research group discovered the Lucy of microbiology last spring.

 

 

The bridge between the prokaryotes and eukaryotes

The microbiological sciences have always been characterized by an almost evil irony. Despite the wealth of knowledge we have managed to extract from microbial lives, an estimate of about 98% of all microorganisms are unculturable in our laboratories (probably due to fastidious, hard-to-balance/hard-to-mimic, nutrient requirements and growth environments) (11). This means that our understanding of the microbial life on earth is based on a fraction of the approximately 2% of the species that can be grown in laboratories. By 2013, merely 10 599 prokaryotic species had been characterized and submitted to our data banks (12). In comparison, researchers have cataloged about 800 000-1 200 000 000 species of insects (13).

 

Keeping this mind, the reason we lack a better resolution of the tree of life could potentially be due to our inability to study the absolute majority of the microorganisms. The species might not be extinct. They just might be hiding in plain sight.

 

But, new methods are continuously developed to address this very issue. Not least, the rapidly advancing DNA-sequencing technology has provided us with powerful tools to study the so-called “non-culturable” prokaryotes. One method, called metagenomics, allows the analysis of all of the DNA found in any given sample – a few drops of seawater, a few grams of soil, or a fraction of the human intestinal content and so on and so forth. Although 98% of the microorganisms in the sample will not grow in our laboratories, we can nevertheless study their genes and genomes with metagenomics. This method has really opened up the field and regularly leads to breakthroughs in our understanding of the microbial life in our surroundings.

 

Now then, to the study that caused this long exposition: the Spang et al. article in Nature in May of 2015 (1).

 

The researchers – a collaborative team composed of groups from the University of Bergen, University of Groningen, University of Vienna and University of Uppsala – examined the microbial diversity of hydrothermal vent (hot water springs) in deep-sea sediments at depths of over 3000 m. Using metagenomics, they stumbled across a new group of non-culturable, and previously uncharacterized, archaea. With sophisticated bioinformatics methods, the researchers managed to piece together the genome of a new so-called Lokiarchaeum.

 

What they then observed was that the Lokiarchaea was a much more complex cell than any other class of archaea known to date. It has actin cytoskeleton (a type supporting structure in the cell), promordial vesicle traffic (advanced form of intracellular transport system in which specific molecules are sent to specific locations), ubiquitin modifications (a way to modify proteins), Ras GTPases (enzymes that perform key chemical processes in the cells). These features typically characterize eukarya and had never previously been observed to be simultaneously present in one prokaryote. The Lokiarchaea are much more closely linked to the eukaryotic cell than any other known non-eukarya.

 

As a twist of fate, the newly characterized species was isolated near a mid-Atlantic hydrothermal vent called ”Loki’s castle”. Loki, of course, is the sly Norse god and he became the namesake for this new class of archaea. The authors write:

 

The proposed naming of the Eukarya-affiliated candidate phylum Lokiarchaeota and the Lokiarchaeum lineage is made in reference to the sampling location, Loki’s Castle, which in turn was named after the Norse mythology’s shape-shifting deity Loki. Loki has been described as ‘‘a staggeringly complex, confusing, and ambivalent figure who has been the catalyst of countless unresolved scholarly controversies’’, in analogy to the ongoing debates on the origin of eukaryotes” (1).

 

🙂

 

Skärmavbild 2015-12-03 kl. 16.14.03

A schematic representation of physiological and phylogenetic relationships between the Lokiarchaeota and eukarya. Picture used courtesy of Nature (14).

 

When analyzing the phylogeny of the Lokiarchaea, the researchers saw that this new branch of life clustered very closely to the eukaryotic lineage – one can say that they are cousins. These findings considerably strengthen the hypothesis that eukaryotic cell originated from an archaeal background, and that the tree of life in reality only has two major branches: bacteria and archaea. Eukarya is thus a further outbranch from the archaeal lineage. Us eukaryotic organisms have sprung from a Lokiarchaea-like species. Lucy was found.

 

One last important implication of this study: it is known that the eukaryotic cell is in essence a hybrid. There is strong evidence suggesting that the important organelle known as the mitochondrion (the energy producing power plants of the eukaryotic cell), and in the case of plants also the chloroplast (the organelle that carries out photosynthesis), are originally bacteria that were engulfed by a bigger (all signs pointing to archeal) cell and degenerated into cell organelles. Among other things that support this is the fact that they harbor some of the DNA required for their functions inside themselves instead of in the cell nucleus, as they would if they had been a separate life form that was introduced into a bigger cell. The genes they harbor within themselves are also much more closely related to bacterial genes than those found in the nucleus. This hybrid hypothesis is called the endosymbiotic theory and is practically fully accepted in the scientific community.

 

But – and this is a big but – the details and the mechanisms of the symbiogenesis are not worked out. Among other things, researchers have not previously been able to explain how an (at this point presumed) archaeum could have ”swallowed” bacteria. Cellular engulfment, or phagocytosis as the absorption of large external materials is called, is not a random event but requires a specific type of cellular machinery driven by an actin cytoskeleton. But as the observant reader might recollect from earlier in the text, this is exactly the type of machinery now identified to be present in the Lokiarchaea. The ability to phagocytose may explain how an ancient archaeum took up the bacteria that came to be mitochondrion and chloroplast, respectively.

 

To summarize, Spang et al. have identified a new species from deep-sea sediments that sits closely to the fork that divides the prokaryotic and eukaryotic branches of life; the missing link that has been sought for decades. With this, they also redefined what was known about archaeal biology, discovered that certain complex cellular processes can indeed also occur in prokaryotes and enabled more specific studies of the eukaryotic cell’s evolutionary origin. The researchers deserve a much credit for their outstanding contributions to evolutionary sciences.

 

Finally, nearly 40 years after the archaea were first described as a separate domain of life on Earth, these fascinating organisms are still virtually unknown to the general public. If archaeal biology is not interesting enough in itself (which it is), then at least the realization that we have emerged from this neglected branch of the tree of life should provide any additionally needed reason to pay the archaea more attention in the future.

 

After all, they’re family.

 

 

UPDATE

Since I wrote this text a couple of months ago, two new studies have been published that deserve some attention in this context.

 

Firstly, Pittis & Gabaldón published a study in Nature titled “Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry”  in which the researchers show that, judging by their data, the eukaryotic nucleus predates the mitochondria. Meaning that somewhere, perhaps, an archaeum with a cell nucleus is floating around, waiting to be found. The question then arises if that organism is strictly eukaryotic or not…

 

Secondly, a study published in Nature Microbiology published the most up to date and expanded phylogenetic tree to date. In this case, the proverb “a picture says more than a thousand words” rings very true, and I’ll leave you at that.

Figure 1

 

 

References

  1. Spang, A. et al. 2015. Complex archaea that bridge the gap between prokaryotes and eukaryotes, Nature.
  2. Carroll, S.B. 2014. Brave Genius. Crown Publishers, NY, USA.
  3. Darwin, C. 1859. On the Origins of Species. John Murray, UK.
  4. Peretó, J. et al. 2009. Charles Darwin and the Origin of Life. Origins of Life and the Evolution of the Biosphere.
  5. Haeckel, E. 1887. The History of Creation Vol II, D. Appleton and Company, NY, USA.
  6. Meredith, R.W et al. 2011. Impacts of the Cretaceous Terrestrial Revolution and KPg Extinction on Mammal Diversification. Science.
  7. Boyden, A. 1942. Systematic Serology: A Critical Appreciation. Physiological Zoology,
  8. Morell, V. 1997. Microbiology’s Scarred Revolutionary. Science. Proc Natl Acad Sci U S A.
  9. Woese, C.R. et al. 1977. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. PNAS.
  10. Albers, S.V. et al. 2013. The legacy of Carl Woese and Wolfram Zillig: from phylogeny to landmark discoveries. Nature Reviews in Microbiology.
  11. Wade, W. 2002. Unculturable bacteria—the uncharacterized organisms that cause oral infections. Journal of the Royal Society of Medicine.
  12. www.bacterio.net/-number.html (info obtained 2015-12-02)
  13. Stewart, E. J. 2012. Growing Unculturable Bacteria. Journal of Bacteriology.
  14. Embley T.M. et al. 2015. Evolution: Steps on the road to eukaryotes. Nature.