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Evolutionary rationale behind migration proteins

Evolutionary rationale behind migration proteins


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Tumor cells are able to migrate due to specific migration proteins. What is their evolutionary origin? Or are they simply deregulated?


This would be a very long answer but just to give you some hints, the migrational mechanisms are already there and the cancerous cells makes use of them to metastasise. So in short its deregulation. What is under selection pressure tho are cancerous cells themselves to constantly change and evade cellular fail safes which kill (apoptosis) uncontrollably replicating cells. You can find out about this here (http://www.nature.com/onc/journal/v22/n42/abs/1206757a.html)


The Lost Eukaryote: an introduction to cellular evolution

The most fundamental divide in the diversity of living creatures is arguably the one between prokaryotes (=bacteria*) and eukaryotes (the tiny island of cumbersomely complex cells that consists of protists. And a couple insignificant lineages that are hardly worth talking about). Much of the earth's biota seems perfectly content with small, streamlined genomes and similarly small, streamlined cell architecture. All but one group, that for some odd reason ended up with a membrane-bound package of a junky genome we call the nucleus. The nucleus, in turn, is but a spokes person -organelle for the massive changes in cellular architecture that occurred in the transition from prokaryotic to eukaryotic forms -- a feature that most likely arose with the changes rather than initiating them. The most prominent features present in all eukaryotes are the actin and tubulin cytoskeleton, endomembrane trafficking (enabling phagocytosis) and mitochondria or some form thereof. Unfortunately (or fortunately, as it keeps us employed?), most of these features appear to have been already present and well-developed in the last common ancestor of all known eukaryotes, thereby depriving us of a convenient grade from which to infer how these structures actually evolved. Once upon a time, it was thought that some anaerobic eukaryotes lacked mitochondria and diverged from the aerobes before the mitochondrion was 'enslaved' through endosymbiosis in the latter (oddly enough, early ribosomal DNA trees even supported that, but that's a story for another day). However, it later turned out that even the mitochondrion was already present in the last common ancestor, and thus when we work our way back to reconstruct the evolution of the eukaryotic cell, we are stuck with a fairly modern cell that seemingly erupts spontaneously from a bacterial sea. Odd and unsettling to say the least.

*Yeah, yeah, Archaea included, we can argue about that later.

As a protistologist and some sort of a cell biologist by modest training, I am particularly interested in cellular evolution. In other words, while some focus on the evolution of macroscopic structures like wings and organs, and others look at molecular evolution of proteins and DNA sequences, I am especially fascinated by the in-between, or how subcellular structures themselves evolve. Unlike molecular biologists, we don't have the luxury of compressing the bulk of our data into sequences, and unlike developmental biologists, we can't really fiddle with gene expression patterns and play with a variety of well-established mutants, both natural (visible diversity) and lab-generated. This is partly why there's a chance you probably never heard of evolutionary cell biology as a field. The other big problem is that much of cellular diversity is, in fact, microbial, and microbial eukaryotes are barely studied (yeasts excluded -- but they're secondarily unicellular anyway, and really, really weird). It is in the unicellular protist realm where the cell is at its finest, for it cannot cower behind the multitudes of defective cell types of a multicellular organism to get by, and must be largely self-sufficient. (This is illustrated further by the higher average complexity (diversity of cell parts) in a unicellular cell than that of multicellular organisms (McShea 2002 Evolution)) Not only are these unicellular organisms cellularly complicated, they're also quite diverse. Bacteria most definitely have a cell biology of their own, but that has become recognised only recently, with the advent of fluorescent, and now super-resolution, light microscopy -- where one can finally track labelled proteins in a living cell. Thus, for the moment, evolutionary cell biology is ultimately the cell biology of protists in light of evolution.

Of course, just comparing cell structures and marvelling at their diversity isn't really all there is to exploring the evolution of something. Even reconstructing ancestral states is just the beginning. Evolutionary biology ultimately pursues mechanisms -- the more general, the better. We could simply assume evolution is adaptation and make up stories as we go along (not entirely unpopular in some circles), but that wouldn't be good science. Evolution involves introduction of variation through mutation (with its own associated biases) as well as sorting thereof nor only through selection, but also by drift and migration.

Furthermore, heritability is a key required component in evolutionary change, and here we may even get something interesting: transmission of information from one cell to the next (generationally) is not only genomic (or genetic), but also depends on a spatial component. If you simply express a genome in a lipid vesicle, the proteins will not magically self-assemble into a working cell. A chunk of necessary information is directed by the patterning in the cell preceding the division. Extra-nuclear (or extra-genomic) cellular inheritance is not a mere figment of speculative imagination -- it has been demonstrated in ciliates in a landmark experiment by Tracy Sonneborn and Janine Beisson: a row of cilia was inverted surgically (presumably without affecting the genome, of course) in a Paramecium, and this strain with a backwards row of cilia persists to this very day, despite multiple genetic outcrossings (Beisson & Sonneborn 1965 PNAS)! Several of Sonneborn's deciples have continued the work on cytoplasmic inheritance in ciliates, with some fascinating results. However, molecular work on poorly-established model organisms is difficult and frustrating, and until recently bordered on insanity. Unfortunately, just as the tools for doing molecular and cell biology on more obscure organisms are greatly improving (10 years ago, you couldn't just sequence a genome on a whim. ), the field has largely. retired.

If there is a channel of inheritance that occurs in parallel with classical genetics, this opens up a whole new jungle of tantalising questions and models waiting to be described and later discarded in favour of better ones. While classical quantitative genetics (which studies the inheritance of visible, measurable traits from generation to generation) is a fairly established and well-studied field at this point, a parallel epigenetic system of heritability would call for expansion of the field to include non-genomic quantitative genetics, where it gets rather tricky due to lack of direct digital coding sequences. Of course, if such a thing were to be pursued and studied, it would have to be in unicellular organisms, for they don't have that pesky bottleneck where the entire multi-million celled creature has to fit through a fertilised egg or seed for later re-patterning. Essentially, this would call for an evolutionary developmental biology of the single cell. While all cells go through something resembling classical development in principle in at least some stage of their lives, we don't typically think of development on a cellular level. We really should.

Enough with the long-winded theoretical introduction. What, if anything, can we say about the grandest scale of eukaryotic cellular evolution, or that nagging question of how eukaryotes evolved? Unfortunately, as mentioned above, the picture is a little unsettling. That last common ancestor of ours was simply too complex! (creationist quotemining in 3. 2. 1)

[caption align="aligncenter" caption="It appears that the last eukaryotic common ancestor (LECA), of all currently known living eukaryotes, has been a fairly sophisticated cell with a nucleus and a mitochondrion, as well as elaborate cytoskeletal and membrane trafficking systems. Presumably, the first eukaryotic common ancestor was drastically less complicated, but its nature remains elusive, and all but one of its descendants. lost. (Also see Field & Dacks 2009 Curr Op Cell Biol)(abbreviations are for major eukaryotic supergroups, in no particular order: Ex - Excavates Op - Opisthokonts Am - Amoebozoans SAR - Stramenopile-Alveolate-Rhizaria clade Arch - Archaeplastids Ha - "Hacrobia")"][/caption]

Not only does LECA appear to possess a mitochondrion and a modern nucleus, but it already has a sophisticated membrane trafficking system, a cytoskeleton, capacity to devour prey by phagocytosis, a eukaryotic cell cycle regulation system, meiotic sex, and even a flagellum. Not only does it have modern-looking structures, but it seems to have already used many of the same molecular components used in a variety of living eukaryotes today. As an aside, you may perhaps recall having learned cell biology going structure by structure: there's an endoplasmic reticulum for making proteins and moving them, a Golgi for sorting them, vacuoles and lysosomes for storage and digestion, a nucleus for DNA. but it's perhaps more productive, and less confusing even, to think of the cell as a network of systems (like the human body), the key ones being metabolic pathways, the genome, cell cycle, the membrane trafficking system and the cytoskeleton, with the rest of the cell emerging from them. (this list is by no means meant to be definitive)

Of course, the first eukaryote-like thing, FECA*, presumably emerged from the bacterial realm. Somehow in the interim, between FECA and LECA, our lineage lost many of its bacterial features (such as a murein wall -- think Gram staining) and picked up all sorts of eukaryotic traits. One would imagine it not being a case where a single proto-eukaryote population just sits around and gradually eukaryifies until it becomes LECA and then explodes into a ton of supergroups -- the pre-LECA eukaryotes were probably diverse and had numerous long-lost offshoots. But somehow, it appears that only one lineage survived to rapidly diversify into modern extant eukaryotes. What where those enigmatic lost eukaryotes? Why did only one lineage survive to bind them all in mystery?

* We could call it them the Lost Eukaryotic Common Ancestors, but the acronym would be confusing.

Unfortunately, where we have a sample size of one in the form of a single phylogenetic event, we are left with little else but mere speculation (the question of the origin of sex falls under the same category). We might be tempted to think the presence of a mitochondrion or its relics in every known eukaryote may allude to mitochondrial symbiosis doing something important. Perhaps a massive selective sweep because this new organelle was that damn awesome. While this may sound reasonable, we have no clear evidence pointing either way. If we knew roughly when eukaryotes arose, we could speculate on some massive environmental change, perhaps a mass extinction where just by chance a single lineage survived. But our estimates for the origin of eukaryotes range from 0.8-3.5 billion years ago, in the wildest estimates. The likeliest time period in my irrelevant opinion, based on fossils and molecular clocks, would be the early Mesoproterozoic or the late Paleoproterozoic (

1.2-1.8 billion years) -- a time period still poorly understood. Hell, at times we can hardly tell whether a microfossil is even biotic in origin, let alone discern what made it!

I have probably convinced you by now that both the question of how cells evolve and the issue of the very origin of eukaryotes are thoroughly impossible to address. Usually when people write about science, the story works towards gradually clarifying one conundrum or another. Yes, there is often the occasional setback and an annoyingly unfitting data point that rudely asserts its foul presence in the midst of your otherwise beautiful hypothesis. But the topic of eukaryotic evolution is a whole other type of story -- in fact, while the protistan phylogeny has been clearing up over the past decade, the question of how they got there in the first place slipped further and further away. And the recent adventures in protistan genomes and proteomes only make it worse -- by rendering the Last Eukaryotic Common Ancestor unbearably complex.

But there is hope, and it lies in the bewildering diversity of eukaryotic cells -- as protists. We can still learn how eukaryotic cells evolve, and work on those general principles and models that are the holy grail of evolutionary biology (as much as anything can be holy in science, but we try!). We could perhaps even extrapolate those principles back in time and use the few subtle clues we have to uncover some of the FECA's descendents' path to eukaryocy (fine, eukaryote-hood). In fact, in the next post we'll look at once such case in the evolution of membrane trafficking machinery. We still have a vastness of post-LECA diversity and evolution to address.

Anywhere there is heritable diversity, there is an evolutionary system awaiting attention. Like culture and language, cells are no exception.

The views expressed are those of the author(s) and are not necessarily those of Scientific American.

ABOUT THE AUTHOR(S)

I first encountered the wonders of the protist realm back in childhood, when a murky droplet of pond scum was revealed by the microscope to entail an alien world in its own right. It took another decade to discover there was a field and a community dedicated to these organisms, and I bade farewell to the study of more familiar big things. As a kid I was also fascinated by tales of exploration of the New World, as well as those of fantasy worlds. I was then sad that the age of surveying new landmasses on earth was over, and that human extraterrestrial adventures are unlikely to happen within our lifetimes. It seemed everything was discovered already. But that could hardly be further from the truth -- all that is necessary to begin one's own Age of Exploration is a new approach or perspective, and a healthy does of imagination. Since reality has conjured far more than the human mind alone ever could, science yields a way to write stories much wilder than fiction. All one needs to access the alien world of microbes around (and inside) them is a shift of scale by simple glass sphere.
I'm currently finishing up my undergraduate degree in Vancouver and in transition career-wise, hopefully to end up in graduate school soon. I was born in Russia (and speak the language) and spent most of my life in US and Canada. In addition to protists, I'm fascinated by evolution, including that of culture and languages, diversity and biology of cells and how they self-organise, linguistics and anthropology, particularly of the less talked-about cultures, sociology of science and plenty of totally random things that snag my attention.
Banner image was kindly post-processed and enhanced by my friend: an accomplished comic artist who goes by Achiru.


Evolutionary rationale behind migration proteins - Biology

Pantry staples from the genetic swap meet - May, 2021
To many people, genetically engineered food feels unnatural and repellent: Fish genes in strawberries? No thanks. Opponents often call them "Frankenfoods," suggesting that only a mad scientist could combine genes from different species in this way. But in recent decades, biologists have found that nature itself often plays fast and loose with DNA. Now, new research shows how important this inter-species genetic swap meet has been in grasses, a group that includes food staples like rice, corn, wheat, and sugar cane.

A Pleistocene Puzzle: Extinction in South America
In this comic, you'll follow the investigation of scientists Maria and Miguel as they solve a paleontological mystery. About 11,000 years ago, more than 80% of the large animal species in South America went extinct. Why did it happen? Maria and Miguel study an area in Chile called Ultima Esperanza. They discover many different lines of evidence that point to a warming climate and the arrival of humans as key causes of the extinctions.


2. Conceptual partings and unifications of evolution and development

One of the most central topics of early philosophy of biology in the 1960s and 1970s was the attempt to develop a suitable conceptual framework that would support the parting between development and evolution in line with the central assumption of the Modern Synthesis that evolution is a change in the genetic composition of populations only (Dobzhansky 1951: 16 see also Charlesworth et al. 2017). This means, as a consequence, that development does not (or not in significant ways) causally effect evolution. Over the decades this assumption has been supported by the historically influential conceptual distinction between proximate causes and ultimate causes (Mayr 1961).

2.1 The proximate-ultimate distinction

The dual framework &lsquoproximate vs. ultimate&rsquo provides a qualitative distinction of biological causality (for related distinctions, see J. Baker 1938 Tinbergen 1951, 1963). It holds that biologists who study proximate causes ask how questions about individual developmental processes. Thus, functional biologists interested in such proximate causes study how systems work. Instead, evolutionary biologists that study ultimate causes ask why questions, like why phylogenesis has produced particular evolutionary functions. According to this distinction, at least on the surface, proximate causes resemble Aristotelian efficient causes while ultimate causes resemble Aristotelian final causes. To illustrate this distinction, Mayr (1961) draws on an example of avian migration. Migration can be studied by asking how bird migrate (i.e., how they develop skills like navigation) or why they migrate (i.e., due to what selective advantage). These two investigations are understood to be both important and complementary. However, they should be treated as distinct from one another.

The proximate-ultimate distinction can be given an epistemic or ontological reading. First, authors have interpreted it as distinguishing different kinds of explanations (Amundson 2005 Calcott 2013 Scholl & Pigliucci 2015). This epistemic reading includes that how questions cannot be addressed by explanations citing ultimate causes (i.e., telling a story of adaptation) and that why questions cannot be addressed by explanations citing proximate causes (i.e., telling a story of trait development). Second, authors have interpreted this distinction as one between different ontological classes of causes working in ontogenetic and phylogenetic processes (Laland et al. 2013a). This ontological reading is backed up theoretically by Weismann&rsquos concept of the separation of germ line and soma, which provides a demarcation line between two distinct classes of causes. To this day, biologists and philosophers have not reached a consensus on how exactly the division &lsquoproximate-ultimate&rsquo or &lsquohow-why&rsquo should be understood, epistemically or ontologically (Francis 1990 Dewsbury 1992, 1999 Sterelny 1992 Beatty 1994 Ariew 2003). Despite this lack of agreement this framework has been applied in various fields, from evolutionary biology (E. O. Wilson 1975 [2000: 23]), evolutionary psychology (Daly & Wilson 1978 Crawford 1998) and behavioral ecology (Morse 1980: 92&ndash95) to human sciences, like in human cooperation (Marchionni & Vromen 2009) and developmental psychology (Lickliter & Berry 1990). Especially in evolutionary biology it has contributed to mainstream causal reasoning for a long time, even among evolutionary biologists interested in developmental processes (see, e.g., Maynard Smith 1982: 6).

2.2 The integration of proximate and ultimate causes

There has been constant criticism of the proximate-ultimate distinction (since even before Mayr 1961), and against its underlying idea to downgrade the explanatory or causal relevance of development to evolution. More recently, the discussion of this issue gained pace through new findings in fields such as epigenetics, evo-devo and niche construction theory (Thierry 2005 Laland et al. 2011, 2013a, 2013b Haig 2011, 2013 Scott-Phillips et al. 2011 Dickins & Rahman 2012 Guerrero-Bosagna 2012 Calcott 2013 Dickins & Barton 2013 Gardner 2013 Mesoudi et al. 2013 Martínez & Esposito 2014 Scholl & Pigliucci 2015 Baedke 2018 Uller & Laland 2019). In this context, some scholars argue that the proximate-ultimate distinction stands &ldquoat the center of some of contemporary biology&rsquos fiercest debates&rdquo (Laland et al. 2011: 1512) about the role of developmental plasticity, niche construction and inclusive inheritance for evolutionary trajectories. Participants in this debate have argued that we should, due to different epistemic or heuristic reasons, keep Mayr&rsquos proximate-ultimate distinction (Scott-Phillips et al. 2011 Dickins & Barton 2013) or a revised or reinterpreted form of it (Scholl & Pigliucci 2015 Otsuka 2015), expand it by a third intermediate form of explanations (Haig 2013), or replace it with a concept of &lsquoreciprocal causation&rsquo (Laland et al. 2011, 2013a, 2013b, 2015 Mesoudi et al. 2013). In line with earlier philosophical work (Oyama 1985 Keller 2010 Griffiths & Stotz 2013), the latter idea of reciprocal causation should allow describing the feedback processes between causal factors in evolving systems. This includes organisms&rsquo capacity of phenotypic plasticity or, more specifically, their activities to alter selection pressures. Paradigmatic feedback cases are niche construction behaviors of organisms that modify their environments and thus shape natural selection pressures working on them. In other words, reciprocal causation holds that organisms are not only effects of adaptive processes, but also causal starting points of evolutionary trajectories. In this sense this framework argues against the causal and/or explanatory asymmetry claim of the proximate-ultimate distinction. It highlights the important role of development for evolution.

Against this new approach, scholars have argued that reciprocal causation does, in fact, not pose any conceptual challenges for evolutionary biology, as it has been included since quite some time ago in the field (Svennson 2018). A true challenge, however, is to develop this idea into a methodologically sound framework that allows studying and modeling complex non-linear organism-environment relations. Other have cast doubt on the central causal role the unit of the organism is supposed to play in this reciprocity framework (Baedke 2019a), or questioned whether this conceptualization can, in fact, capture all causal dependency relations of interest for evolutionary biology (Martínez & Esposito 2014 Scholl & Pigliucci 2015). Moreover, some argued that also this framework relies on the dichotomy between development and evolution (Dickins & Barton 2013 Martínez & Esposito 2014) and that it is not conducive to successful biological science, as it does not lead to falsifiable questions (Dickins & Rahman 2012) and bleeds proximate and ultimate explanations into each other so that their distinction becomes meaningless (Gardner 2013 one should mention, however, that this might be the very aim of this approach). More generally, it has been requested that advocates of this approach should provide more conceptual clarifications on what reciprocal causation actually is supposed to mean (Buskell 2019).

Besides distinguishing development and evolution in a qualitative manner as proximate and ultimate causal processes, a less common attempt is to quantitatively distinguish (or relate) the two. Here, especially distinctions based on the rates or time scales on which different developmental and biological processes occur have been made (see the entry levels of organization in biology). For example, Conrad H. Waddington (1957) developed a hierarchical model of time scales that includes biochemical processes on lower molecular levels of organization with a faster rate, medium paced processes of development on a medium level, and evolutionary processes on higher levels with a slower rate. According to such a view, evolutionary processes are simply processes occurring with a different rate and thus at a different level than developmental ones. Thus, they differ gradually rather than in kind. Rate-based distinctions have been described to be consistent with the ultimate-proximate framework (when interpreting it as one that distinguishes different timescales of phenotypic change see Francis 1990 Haig 2013) or as different from proximate-ultimate distinctions (Baedke & Mc Manus 2018). In addition, time-scale (or size-scale) conceptualizations have been applied for developing methodologies and multi-scale modeling that integrate, among others, developmental and evolutionary processes (S. Levin 1992 Green & Batterman 2017 Duckworth 2019).


Origin of Life on Earth

The origin of life is a mystery, the ultimate chicken-and-egg conundrum (R Service, 2015). When you and fellow students together discussed the defining characteristics of life, you probably included reproduction and hereditary information, transformation of energy, growth and response to the environment. You may also have said that, at least on Earth, all life is composed of cells, with membranes that form boundaries between the cell and its environment, and that cells were composed of organic molecules (composed of carbon, hydrogen, nitrogen, oxygen, phosphate, and sulfur – CHNOPS). The conundrum is that, on Earth today, all life comes from pre-existing life. Pasteur’s experiments disproved spontaneous generation of microbial life from boiled nutrient broth. No scientist has yet been able to create a living cell from organic molecules. So how could life have arisen on Earth, around 3.8 billion years ago? (Keep in mind the scale of time we’re talking about here – the Earth is 4.6 billion years old, so it took almost a billion years for chemical evolution to result in biological life.) How can this question be addressed using the process of scientific inquiry?

Origin of life studies

Although scientists cannot directly address how life on Earth arose, they can formulate and test hypotheses about natural processes that could account for various intermediate steps, consistent with the geological evidence. In the 1920s, Alexander Oparin and J. B. S. Haldane independently proposed nearly identical hypotheses for how life originated on Earth. Their hypothesis is now called the Oparin-Haldane hypothesis, and the key steps are:

  1. formation of organic molecules, the building blocks of cells (e.g., amino acids, nucleotides, simple sugars)
  2. formation of polymers (longer chains) of organic molecules, that can function as enzymes to carry out metabolic reactions, encode hereditary information, and possibly replicate (e.g., proteins, RNA strands),
  3. formation of protocells concentrations of organic molecules and polymers that carry out metabolic reactions within an enclosed system, separated from the environment by a semi-permeable membrane, such as a lipid bilayer membrane

The Oparin-Haldane hypothesis has been continually tested and revised, and any hypothesis about how life began must account for the 3 primary universal requirements for life: the ability to reproduce and replicate hereditary information the enclosure in membranes to form cells the use of energy to accomplish growth and reproduction.

1. How did organic molecules form on a pre-biotic Earth?

Miller-Urey experiment
Stanley Miller and Harold Urey tested the first step of the Oparin-Haldane hypothesis by investigating the formation of organic molecules from inorganic compounds. Their 1950s experiment produced a number of organic molecules, including amino acids, that are made and used by living cells to grow and replicate.

Miller-Urey experiment, Wikimedia Commons illustration by Adrian Hunter

Miller and Urey used an experimental setup to recreate what environmental conditions were believed to be like on early Earth. A gaseous chamber simulated an atmosphere with reducing compounds (electron donors) such as methane, ammonia and hydrogen. Electrical sparks simulated lightning to provide energy. In only about a week’s time, this simple apparatus caused chemical reactions that produced a variety of organic molecules, some of which are the basic building blocks of life, such as amino acids. Although scientists no longer believe that pre-biotic Earth had such a reducing atmosphere, such reducing environments may be found in deep-sea hydrothermal vents, which also have a source of energy in the form of the heat from the vents. In addition, more recent experiments – that used conditions that are thought to better reflect the conditions of early Earth – have also produced a variety of organic molecules including amino acids and nucleotides (the building blocks of RNA and DNA) (McCollom, 2013).

The video below gives a nice overview of the rationale, setup, and findings from the Miller-Urey experiment (although it incorrectly overstates that Darwin showed that relatively simple creatures can gradually give rise to more complex creatures).

Organic molecules from meteors

Each day the Earth is bombarded with meteorites and dust from comets. Analyses of space dust and meteors that have landed on Earth have revealed that they contain many organic molecules. The in-fall of cometary dust and meteorites was far greater when the Earth was young (4 billion years ago). Many scientists believe that such extra-terrestrial organic matter contributed significantly to the organic molecules available at the time that life on Earth began. The figure below from Bernstein 2006 shows the 3 major sources of organic molecules on pre-life Earth: atmospheric synthesis by Miller-Urey chemistry, synthesis at deep-sea hydrothermal vents, and in-fall of organic molecules synthesized in outer space.

2. Formation of organic polymers

Given a high enough concentration of these basic organic molecules, under certain conditions these will link together to form polymers (chains of molecules covalently bonded together). For example, amino acids link together to form polypeptide chains, that fold to become protein molecules. Ribose, a 5-carbon sugar, can bond with a nitrogenous base and phosphate to a nucleotide. Nucleotides link together to form nucleic acids, like DNA and RNA. While this is accomplished now by enzymes in living cells, polymerization of organic molecules can also be catalyzed by certain types of clay or other types of mineral surfaces. Experiments testing this model have produced RNA molecules up to 50-units long, in only a 1-2 week period of time (Ferris, 2006).

Enzymatic activity and hereditary information in one polymer: the RNA World hypothesis

The discovery by Thomas Cech that some RNA molecules can catalyze their own site-specific cleavage led to a Nobel prize (for Cech and Altman), the term “ribozymes” to denote catalytic RNA molecules, and the revival of a hypothesis that RNA molecules were the original hereditary molecules, pre-dating DNA. For origin-of-life researchers, here was the possibility that RNA molecules could both encode hereditary information, and catalyze their own replication. DNA as the first hereditary molecule posed real problems for origin-of-life researchers because DNA replication requires protein enzymes (DNA polymerases) and RNA primers (see page on DNA replication), so it’s difficult to envision how such a complex hereditary system could have evolved from scratch. With catalytic RNA molecules, a single molecule or family of similar molecules could potentially store genetic information and replicate themselves, with no proteins needed initially.

Populations of such catalytic RNA molecules would undergo a molecular evolution conceptually identical to biological evolution by natural selection. RNA molecules would make copies of each other, making mistakes and generating variants. The variants that were most successful at replicating themselves (recognize identical or very similar RNA molecules and most efficiently replicate them) would increase in frequency in the population of catalytic RNA molecules. The RNA world hypothesis envisions a stage in the origin of life where self-replicating RNA molecules eventually led to the evolution of a hereditary system in the first cells or proto-cells. A system of RNA molecules that encode codons to specify amino acids, and tRNA-like molecules conveying matching amino acids, and catalytic RNAs that create peptide bonds, would constitute a hereditary system much like today’s cells, without DNA.

At some point in the lineage leading to the Last Universal Common Ancestor, DNA became the preferred long-term storage molecule for genetic information. DNA molecules are more chemically stable than RNA (deoxyribose is more chemically inert than ribose). Having two complementary strands means that each strand of DNA can serve as a template for replication of its partner strand, providing some innate redundancy. These and possibly other traits gave cells with a DNA hereditary system a selective advantage so that all cellular life on Earth uses DNA to store and transmit genetic information.

Still, even today, ribozymes play universal and central roles in cellular information processing. The ribosome is a large complex of RNAs and proteins that reads the genetic information in a strand of RNA to synthesize proteins. The key catalytic activity, the formation of peptide bonds to link two amino acids together, is catalyzed by a ribosomal RNA molecule. The ribosome is a giant ribozyme. Since ribosomes are universal to all cells, such catalytic RNAs must have been present in the Last Universal Common Ancestor of all current life on Earth.

Visit the http://exploringorigins.org/ribozymes.html page to view the first ribozyme from Tetrahymena, discovered by Tom Cech, and the structure of the ribosomal RNAs.

The http://exploringorigins.org/nucleicacids.html page has videos of polymerization of RNA from nucleotides, template-directed RNA synthesis, and a model of RNA self-replication.

The video below explains the rationale behind the RNA world hypothesis and briefly describes some of the findings from different RNA world experiments.

3. Protocells: self-replicating and metabolic enzymes in a bag

All life on Earth is composed of cells. Cells have lipid membranes that separate their inner contents, the cytoplasm, from the environment. The lipid membranes allow cells to maintain high concentrations of molecules like nucleotides needed for self-replicating RNAs to function more efficiently. Cells also maintain large differences in concentration (concentration gradients) of ions across the membrane to drive transport processes and cellular energy metabolism.

Lipids are hydrophobic, and will spontaneously self-assemble in water to form either micelles or lipid bilayer vesicles. Vesicles that enclose self-replicating RNAs and other enzymes, take in reactants across the membrane, export products, grow by accretion of lipid micelles, and divide by fission of the vesicle, are called proto-cells or protobionts and may have been the precursors of cellular life.

The video below explores the differences between chemical and biological evolution, and highlights proto-cells as an example of chemical evolution.

At what point would evolutionary processes, such as natural selection, begin to drive the origin of the first cells?

Biological evolution is restricted to living organisms. So once the first cells, complete with a hereditary system, were formed, they would be subject to evolutionary processes, and natural selection would drive adaptation to their local environments, and populations in different environments would undergo speciation as gene flow becomes restricted between isolated populations.

However, the RNA World Hypothesis envisions evolutionary processes driving populations of self-replicating RNA molecules or proto-cells containing such RNA molecules. RNA molecules that replicated imperfectly would produce daughter molecules with slightly different sequences. The ones that replicate better, or improve the growth replication of their host proto-cells, would have more progeny. Hence, molecular evolution of self-replicating RNA molecules or proto-cell populations containing self-replicating RNA molecules would favor the eventual formation of the first cells.

References and Resources

Bernstein M 2006. Prebiotic materials from on and off the early Earth. Philos Trans
R Soc Lond B Biol Sci. 361:1689-700 discussion 1700-2. PubMed
PMID: 17008210 PubMed Central PMCID: PMC1664678.


Key recent findings and their impact on the field

Insights into anteroposterior axis formation and gastrulation

In Drosophila, anteroposterior (AP) axis formation and patterning are regulated by maternal gene products that are deposited and localised in the eggs. However, the specific factors and regulatory mechanisms involved in defining the AP axis in insects and other arthropods have evolved in different lineages: for example, the transcription factor encoded by bicoid (bcd) is only found in higher flies like Drosophila (McGregor, 2005). Investigating Parasteatoda development could eventually help to determine how the AP axis might have been determined ancestrally in arthropods, and recent studies of early embryogenesis in this spider represent an excellent platform to address this question.

In Parasteatoda, AP axis determination is concomitant with the formation of the germ disc during stage 3. The periphery or rim of the disc represents the anterior, whereas the centre represents the posterior, which subsequently develops into the caudal lobe during stages 4-7 (Fig. 4A). The embryo at the early germ disc stage is thus radially symmetrical. After the formation of the germ disc, gastrulation begins at the posterior end of the embryo, beginning with the formation of the blastopore in the centre of the germ disc (Montgomery, 1909) (Fig. 4). As also observed in other spiders, this posterior region of internalising cells leads to the formation of a multilayered primary thickening (see Glossary, Box 1 Fig. 4) (Anderson, 1973). Interestingly, a second region of internalising cells located at the rim of the stage 5 germ disc (Fig. 4A), has also been observed in Parasteatoda (Kanayama et al., 2011 Montgomery, 1909 Oda et al., 2007).

Development of Parasteatoda from germ disc to germ band. (A) Schematic overview of stages 4 to 8 from a lateral (upper) and caudal (lower) view. In all lateral views anterior is to the left (as indicated by dashed arrow in stage 4, early). Dorsal is up from stage 5 onwards in both views (as indicated by dashed arrow in stage 5). The developing embryonic tissue in all stages is coloured light brown whereas light grey shading indicates the extra-embryonic region. Dark grey represents the dorsal field (df). Dark brown shading indicates the two regions in which gastrulation takes place: the closing blastopore (bp) at stage 4 and the rim of the germ disc at stage 5. Yellow structures and arrows indicate the initial location, after internalisation and subsequent movements, of endodermal cells (for clarity, the mesoderm is not shown). A special group of endoderm cells form the cumulus mesenchyme (CM) that migrates anteriorly as a cluster during stage 5 (black arrow) and degenerates during stage 6. At stage 8, arrows indicate segments in the head region, and circles indicate segments in the leg-bearing prosomal region. (B) Schematic cross-section of the centre of the germ disc [based on a similar scheme in Oda et al. (Oda et al., 2007)]. Stages correspond to the stages represented directly above in A, and dorsal is up from stage 5 onwards. Cellular expression of given genes and proteins is indicated by different colours as shown in the key. A putative gradient of the Wnt8 ligand is indicated in purple. See main text for details. cl, caudal lobe pt, primary thickening SAZ, segment addition zone.

Development of Parasteatoda from germ disc to germ band. (A) Schematic overview of stages 4 to 8 from a lateral (upper) and caudal (lower) view. In all lateral views anterior is to the left (as indicated by dashed arrow in stage 4, early). Dorsal is up from stage 5 onwards in both views (as indicated by dashed arrow in stage 5). The developing embryonic tissue in all stages is coloured light brown whereas light grey shading indicates the extra-embryonic region. Dark grey represents the dorsal field (df). Dark brown shading indicates the two regions in which gastrulation takes place: the closing blastopore (bp) at stage 4 and the rim of the germ disc at stage 5. Yellow structures and arrows indicate the initial location, after internalisation and subsequent movements, of endodermal cells (for clarity, the mesoderm is not shown). A special group of endoderm cells form the cumulus mesenchyme (CM) that migrates anteriorly as a cluster during stage 5 (black arrow) and degenerates during stage 6. At stage 8, arrows indicate segments in the head region, and circles indicate segments in the leg-bearing prosomal region. (B) Schematic cross-section of the centre of the germ disc [based on a similar scheme in Oda et al. (Oda et al., 2007)]. Stages correspond to the stages represented directly above in A, and dorsal is up from stage 5 onwards. Cellular expression of given genes and proteins is indicated by different colours as shown in the key. A putative gradient of the Wnt8 ligand is indicated in purple. See main text for details. cl, caudal lobe pt, primary thickening SAZ, segment addition zone.

In these regions, the earliest cells that ingress at the blastopore and at the anterior of the germ disc express the transcription factor Forkhead (Fkh) (Fig. 4A,B), and have been respectively called the central and peripheral endoderm (Akiyama-Oda and Oda, 2003 Oda et al., 2007). The ingressing endodermal cells at both locations are followed soon after by ingressing mesodermal cells that express twist (twi), which encodes another transcription factor (Fig. 4B see below). Thus, in Parasteatoda embryos, the earliest morphological events along the AP axis are the formation of a germ disc followed by specification of posterior and anterior regions in the germ disc that differentiate endodermal and mesodermal cells with seemingly similar, germ layer-specific, expression profiles.

One question highlighted by this work is what factor or factors initially define AP polarity in Parasteatoda? It has been proposed that Hedgehog (Hh) signalling regulates formation of the germ disc and the AP axis (Akiyama-Oda and Oda, 2010). During stage 3, when the germ disc forms, hh is expressed in cells in the presumptive extra-embryonic region. However, during stages 4 and 5, the expression of this gene is confined to the rim of the germ disc. Therefore, Hh might form a gradient from the rim to the centre of the germ disc (Akiyama-Oda and Oda, 2010).

Interestingly, although pRNAi against several components of Hh signalling does inhibit migration of the cumulus (see below), these embryos still form a germ disc, with both a blastopore in the centre and an anterior region of gastrulation at the rim. Therefore, although the subsequent patterning of the germ disc is affected when Hh signalling is disrupted, this suggests that there must be other factors responsible for regulating the initial formation of the germ disc and the AP axis.

Insights into dorsoventral axis formation: the cumulus and the conserved role of the BMP pathway

Investigation of dorsoventral (DV) axis formation in Parasteatoda has revealed that this spider uses a novel developmental mechanism involving the migration of an organising centre, and has also highlighted the evolutionarily conserved regulation of DV axis specification by the bone morphogenetic protein (BMP) pathway (Akiyama-Oda and Oda, 2003 Akiyama-Oda and Oda, 2006 Lynch and Roth, 2011).

The migration of the cumulus plays a crucial role in breaking the radial symmetry of the germ disc in Parasteatoda to establish DV polarity and formation of the germ band. Moreover, although the evolutionary origin of the cumulus is debated (Box 3), its importance in the formation of the DV body axis in spiders has actually been known for many decades from transplantation and ablation experiments by Holm (Holm, 1952), who originally proposed that the cumulus forms an organising centre.

Box 3. The evolution of the cumulus

During Parasteatoda embryogenesis, migration of the cumulus mesenchyme sets up the DV axis (reviewed by Oda and Akiyama-Oda, 2008), which is an intriguing example of a migrating embryonic signalling centre (Akiyama-Oda and Oda, 2010). Furthermore, this means that gastrulation precedes DV axis formation in Parasteatoda (Fig. 4A). The reverse is true for many insect species in which gastrulation is localised to the part of the blastoderm that has already been specified as ventral tissue without the involvement of a cumulus (Roth, 2004). Therefore, considering the phylogenetic position of chelicerates at the base of the arthropod tree, it has been proposed that DV axis formation via a cumulus-like mechanism might represent the arthropod ancestral state (McGregor et al., 2008a). Evidence against this hypothesis comes from a recent study of onychophorans, the closest living relatives to arthropods (Fig. 1), in which it was shown that gastrulation takes place along a ventral gastral groove, without the formation of a cumulus (Mayer and Whitington, 2009). Therefore, although the existence of a cumulus in myriapods continues to be unresolved (Brena and Akam, 2011), currently the most parsimonious explanation is that the cumulus evolved after the chelicerate-mandibulate split. However, as a migrating cumulus has also been described in a horseshoe crab (a marine group of chelicerates) (Sekiguchi, 1973), it is likely that this mode of development evolved very early in the chelicerate lineage (Redkin et al., 2008).

In Parasteatoda, the cumulus forms during stage 4 when a subpopulation of the Fkh-expressing endodermal cells at the primary thickening can be distinguished by the expression of a fascin-related gene (Akiyama-Oda and Oda, 2010). At the beginning of stage 5, these cumulus mesenchyme (CM see Glossary, Box 1) cells begin to express decapentaplegic (dpp), which encodes the homologue of vertebrate BMP2/4, and subsequently detach from the primary thickening to migrate anteriorly towards the rim of the germ disc.

The CM cells closely associate with the epithelial cells above their path and induce them, possibly through cytonemes (see Glossary, Box 1), to express phosphorylated Mothers against dpp (pMad). pMad then antagonises the Dpp inhibitor Short gastrulation (Sog) to set up the DV axis (Akiyama-Oda and Oda, 2003 Akiyama-Oda and Oda, 2006). Thus, Parasteatoda uses a similar set of factors to those employed in other metazoans to regulate DV axis formation (Lynch and Roth, 2011).

At the morphological level, the migration of the cumulus breaks radial symmetry of the germ disc progressively from posterior to anterior, specifying the dorsal area of the embryo as it migrates whereas the opposite region of the germ disc becomes ventral (Fig. 4, stage 5). This also involves epithelial cells expressing fkh (Akiyama-Oda and Oda, 2003) and adopting a presumptive extra-embryonic fate known as the dorsal field (see Glossary, Box 1 Fig. 4).

Several recent studies have also provided insights into the molecular mechanisms underlying the migration of the cumulus and the morphogenetic properties of this structure. For example, in dpp-depleted embryos, even though the cumulus migrates normally, radial symmetry is not broken and the dorsal field does not develop (Akiyama-Oda and Oda, 2006). Furthermore, knockdown of several components of the Hh pathway, including the Hh receptor encoded by patched, blocks the migration of CM cells, which suggests that this movement depends on the source of Hh localised at the rim of the germ disc. If this model is true, and assuming that Hh signalling is equally intense from around the circumference of the germ disc, this implies that the initial direction of travel of the cumulus is stochastically determined (Akiyama-Oda and Oda, 2010).

The segment addition zone: insights into segmentation

Like most arthropods, spiders add posterior segments sequentially from the SAZ, although the relative contribution of cell division and cell rearrangements to the production of new segments is not yet known in Parasteatoda. Indeed, despite the importance of the SAZ, the development of this structure and the subsequent production of segments are still not well understood generally among arthropods. However, studies in Parasteatoda have provided new and important information regarding how the formation of the SAZ and the generation of segments are regulated.

Oda and colleagues have shown that the Notch signalling pathway regulates germ layer specification at the embryonic posterior, and that this is crucial for the correct formation of the SAZ (Oda et al., 2007). The gene delta (dl), which encodes a ligand for the Notch signalling pathway, is first expressed in an evenly dispersed ‘salt-and-pepper’ pattern among surface cells in the region of the blastopore that then co-express twi and internalise as mesodermal precursor cells (Fig. 4B). The adjacent cells do not express dl or twi but instead express caudal (cad) and adopt an ectodermal fate. It is thought that this pattern is specified through a process of lateral inhibition, with the original dl-expressing cells inhibiting adjacent cells from adopting a mesodermal fate possibly by directly or indirectly repressing twi expression (Oda et al., 2007). This is supported by the fact that when components of the Notch signalling pathway are knocked down, the number of twi-expressing cells increases, the centre of the germ disc develops into a disorganised cell mass, and cad expression in presumptive ectodermal cells at stage 6 is lost (Oda et al., 2007).

A similar effect is observed when the Wnt8 gene, which encodes one of the subfamilies of secreted ligands for Wnt signalling (Janssen et al., 2010), is knocked down, suggesting that Wnt and Notch signalling together regulate formation of the SAZ (McGregor et al., 2008b). Indeed, pRNAi against either Wnt8 or components of Notch signalling results in truncated embryos without any opisthosomal segments (McGregor et al., 2008b Oda et al., 2007). Curiously, Wnt8 RNAi embryos exhibit an enlargement of the adjacent prosomal segments. Therefore, Wnt8 might form a posterior-to-anterior gradient (Fig. 4B), which is not only involved in the formation of the SAZ but also maintains an undifferentiated population of cells in this tissue that are used in the subsequent addition of opisthosomal segments (McGregor et al., 2009 McGregor et al., 2008b). Furthermore, the dynamic expression pattern of dl in the SAZ and nascent posterior segments of Parasteatoda embryos (Oda et al., 2007), which is blocked when Wnt8 is knocked down (McGregor et al., 2008b), suggests that a clock-like mechanism involving Notch and Wnt signalling, analogous to that observed in vertebrates, regulates segment addition in Parasteatoda.

Interestingly, it has been found that Notch signalling is involved in segmentation in cockroaches (Pueyo et al., 2008), and Wnt8 is required for the formation of posterior segments in beetles (Bolognesi et al., 2008). This suggests that these pathways, together with cad, were components of an ancestral network for posterior development in arthropods (McGregor et al., 2009) and possibly even other animals (Couso, 2009). Note, however, that the precise role of some genes, particularly those encoding Wnt ligands, may have evolved (Janssen et al., 2010), and Notch signalling might not be involved in segmentation in several arthropod lineages, including Tribolium (Aranda et al., 2008 Kainz et al., 2011).

Prosomal segmentation and early patterning

In contrast to Drosophila and other insects, the early embryos of spiders and several other arthropods are cellularised at an earlier stage (Kanayama et al., 2010). This has important implications for patterning because gradients of transcription factors, like the Bcd morphogen gradient in Drosophila embryos, would not be effective in a cellularised blastoderm, and, thus, positional information must be provided by other mechanisms. In Parasteatoda, it has been shown that the patterning and subsequent segmentation of the anterior prosoma are the result of both dynamic and static mechanisms that are initiated early in the germ disc stage. Furthermore, these studies have revealed that prosomal segmentation involves mechanisms that are different to those used to generate opisthosomal segments.

Patterning of the anterior prosoma (up to the pedipalpal segment) requires travelling (Pechmann et al., 2009) and splitting (Kanayama et al., 2011) of a wave of hh and hairy (h) expression. Initially orthodenticle (otd), hh and h are expressed at the periphery of the germ disc at stage 5, and subsequently at the anterior rim of the germ band. At stages 6 and 7, the stripes of otd, hh and h expression are found in a more posterior position and divide into multiple stripes. The travelling and splitting of these expression patterns depends on otd and hh function and is a prerequisite for the correct positioning of segmental gene expression in the embryo. Silencing of otd blocks the initial movement of the normally dynamic anterior stripes of hh and h expression, such that the expression of these genes is restricted to the anterior rim and does not split into stripes. This results in embryos that lack all tissue anterior to the pedipalpal segment (Pechmann et al., 2009). Furthermore, otd-eRNAi cell clones located away from the rim no longer express hh, which suggests that Otd is also required to maintain hh expression during the travelling and splitting phase (Kanayama et al., 2011). Conversely, the expression and activity of otd strongly depends on hh (Akiyama-Oda and Oda, 2010 Kanayama et al., 2011). It has therefore been proposed that spider head segmentation requires an autoregulatory signalling network in which otd is required to regulate dynamically the distribution of patterns of hh signalling sources (Kanayama et al., 2011).

By contrast, patterning of the leg-bearing segments of the spider prosoma depends on a static mechanism that resembles insect gap gene patterning. This involves the spider orthologue of the gap gene hunchback (hb) (Schwager et al., 2009) and the broadly conserved limb-patterning gene Distal-less (Dll), which is not only required for development of the appendages, as expected because this is an evolutionarily conserved function of this gene, but, surprisingly, also acts as a gap gene in Parasteatoda and probably in other spiders (Pechmann et al., 2011). Knockdown of hb or Dll in Parasteatoda entirely removes some leg-bearing segments, giving rise to phenotypes that are highly reminiscent of insect gap phenotypes. These morphological phenotypes correlate with downregulation of the segmentation genes engrailed (en) and hh in the affected region. Although the identity of the upstream factor(s) that regulate hb and Dll in Parasteatoda is not yet known, given the cellular nature of the early spider embryo, it is tempting to speculate that intercellular signalling pathways might also play a role in the activation of these gap genes.

These findings in Parasteatoda provide insights into the evolution of anterior segmentation mechanisms in arthropods and might help us to answer the challenging question of how diversification of developmental mechanisms is related to animal body plan evolution. In this respect, spider development might rely more on intercellular signalling mechanisms than is the case during the syncytial stages of development in Drosophila, and Parasteatoda is a good model for investigating this idea further.


Key recent findings and their impact

When molecular studies of cnidarians were initiated, a major goal was to determine whether the genetic toolkit used to construct the bilaterian embryo (represented primarily by the model systems Drosophila, C. elegans, amphibians, zebrafish and mice) was in place in the ancestor of cnidarians and bilaterians. As we discuss below, recent research on cnidarians using molecular methods has helped to address this and other important questions in developmental biology.

How does the genetic toolkit that is involved in the development of the morphologically simple cnidarians compare to that used in bilaterians?

Despite their relatively simple anatomies, cnidarians have a surprisingly complex genetic toolkit. The first evidence for this came from EST datasets from Acropora and Nematostella (Ball et al., 2004 Kortschak et al., 2003 Miller et al., 2005 Technau et al., 2005), and sequencing of the Nematostella genome corroborated this view (Miller and Ball, 2008 Putnam et al., 2007). A striking example of the complexity of the cnidarian gene set comes from the finding that Nematostella has all of the Wnt family members (except for the Wnt9 subfamily) found in bilaterians (Kusserow et al., 2005 Lee et al., 2006). Comparison of the Nematostella and Hydra genome sequences (browsers are available for both genomes: Hydra, http://hydrazome.metazome.net/cgi-bin/gbrowse/hydra Nematostella, http://www.metazome.net/cgi-bin/gbrowse/Nvectensis) shows that Hydra has undergone considerable gene loss compared with Nematostella (Chapman et al., 2010). Other recent studies have revealed the evolution and expansion of taxon-restricted genes in cnidarians, i.e. genes that have no counterpart in other lineages and which therefore might be involved in the evolution of lineage-specific morphological traits, such as nematocytes (Foret et al., 2010 Hwang et al., 2010 Khalturin et al., 2008 Khalturin et al., 2009 Steele and Dana, 2009 Steele et al., 2011).

Anatomy of a hydrozoan polyp. (A) A Hydra polyp is essentially a two-layered tube, with a ring of tentacles around the mouth opening at the tip of the hypostome. Asexual budding occurs on the lower half of the body column. Interstitial stem cells and nematoblasts are distributed evenly in the body column, below the tentacle ring and above the border of the peduncle, which is the stalk between the budding region and pedal disc. (B) The bilayered cellular organization of a Hydra polyp. Ectoderm and endoderm are separated by an acellular matrix called the mesogloea (gray). All epithelial cells in Hydra are myoepithelial, with myofibers on the basal side (red). In ectodermal epithelial cells (green), the fibers are oriented longitudinally, and in endodermal epithelial cells (pink) they are oriented circumferentially (ring muscle). Most interstitial cells and nematoblast clusters are located between ectodermal epithelial cells. Neurons are found in both the endoderm and ectoderm. Sensory neurons are located between epithelial cells and connect to ganglion neurons (purple), which are at the base of the epithelium on top of the myofibers and sometimes cross the mesogloea. Different types of gland cells, most of which are found in the endoderm, are intermingled between the epithelial cells.

Anatomy of a hydrozoan polyp. (A) A Hydra polyp is essentially a two-layered tube, with a ring of tentacles around the mouth opening at the tip of the hypostome. Asexual budding occurs on the lower half of the body column. Interstitial stem cells and nematoblasts are distributed evenly in the body column, below the tentacle ring and above the border of the peduncle, which is the stalk between the budding region and pedal disc. (B) The bilayered cellular organization of a Hydra polyp. Ectoderm and endoderm are separated by an acellular matrix called the mesogloea (gray). All epithelial cells in Hydra are myoepithelial, with myofibers on the basal side (red). In ectodermal epithelial cells (green), the fibers are oriented longitudinally, and in endodermal epithelial cells (pink) they are oriented circumferentially (ring muscle). Most interstitial cells and nematoblast clusters are located between ectodermal epithelial cells. Neurons are found in both the endoderm and ectoderm. Sensory neurons are located between epithelial cells and connect to ganglion neurons (purple), which are at the base of the epithelium on top of the myofibers and sometimes cross the mesogloea. Different types of gland cells, most of which are found in the endoderm, are intermingled between the epithelial cells.

How do the axes of cnidarians relate to the anterior-posterior and dorsal-ventral axes of bilaterians?

The anterior-posterior (A-P) axis in bilaterians (experimentally best exemplified in mice and flies) is specified by the combinatorial action of Hox genes that are expressed in a staggered manner (the ‘Hox code’ see Glossary, Box 1) along the axis, colinear with their clustered organization in the genome. The presence of a Hox cluster and colinear expression is taken as an indication of a conserved role for Hox genes in A-P body axis specification. Current findings indicate that the evolutionary history of Hox (and ParaHox) genes in cnidarians is complex (involving, for example, secondary losses and dramatically variable expression patterns) and that the history of genome organization for these genes is difficult to reconstruct, particularly as it relates to the Hox and ParaHox clusters in bilaterians. It seems likely, however, that a Hox code does not operate in cnidarians at the oral-aboral axis (Chiori et al., 2009) and that genetic changes over

500 million years of evolution have obscured the relationship of Hox- and ParaHox-related gene function in this phylum to that in bilaterians (Chourrout et al., 2006 Finnerty et al., 2004 Kamm et al., 2006 Thomas-Chollier et al., 2010).

Whereas studies of Hox genes have not been as illuminating as originally hoped with regard to the evolution of axes in metazoans, studies of the Wnt signaling pathway have been. In Hydra, from which genes encoding most of the components of the canonical Wnt pathway have been cloned, seven of the ten Wnt genes identified in Hydra are expressed in the hypostome (the oral dome of the polyp) (Hobmayer et al., 2000 Lengfeld et al., 2009). Moreover, all of the Wnt genes investigated show a staggered spatial expression pattern along the oral-aboral axis of the Nematostella planula larva and the Hydra polyp, suggesting that they are involved in the patterning of this axis (Guder et al., 2006 Kusserow et al., 2005 Lee et al., 2006). However, whether the role of Wnt signaling is to pattern and specify the axis in a Hox-like manner or to control gastrulation and endoderm formation remains a matter of debate, as canonical Wnt pathway activation by LiCl also leads to an expansion of the endoderm during gastrulation (Wikramanayake et al., 2003).

In Clytia, two maternally expressed Frizzled Wnt receptors localize to opposing ends of the egg, where they act to define the oral-aboral axis (Momose and Houliston, 2007). In addition, a maternally expressed Wnt gene accounts, in part, for the observed role of canonical Wnt signaling during early embryonic axis formation in Clytia (Momose et al., 2008). Wnt signaling also appears to play an important role in axial patterning in the embryo and polyp of Hydractinia echinata (Duffy et al., 2010 Plickert et al., 2006). Recent evidence from Hydra suggests an interesting link between canonical and non-canonical Wnt signaling during bud formation (Philipp et al., 2009). In addition to Wnt receptors and ligands, several intracellular components of the canonical Wnt signaling pathway, including Dishevelled and β-catenin, function in cnidarian axis formation and gastrulation (Gee et al., 2010 Lee et al., 2007). Interestingly, chemical perturbation of canonical and non-canonical Wnt signaling suggests that a hierarchical relationship exists between these two pathways during budding of Hydra (Philipp et al., 2009). A recent functional study on Strabismus suggests a crucial role for the Wnt planar cell polarity (PCP) pathway during gastrulation of Nematostella. (Kumburegama et al., 2011).

Thus, in cnidarians, Wnt signaling appears to play a decisive role in establishing the animal/oral pole that subsequently develops into the hypostomal organizer of the polyp. This seems to be one of the oldest conserved developmental mechanisms in animal evolution because in vertebrates and other organisms, canonical Wnt signaling is involved in defining the blastopore (see Glossary, Box 1) or a derivative of it (e.g. the ‘organizer’ in vertebrates) (reviewed by Weaver and Kimelman, 2004). Since Wnt signaling in vertebrates is crucial for posterior development, it is tempting to homologize the A-P axis of vertebrates with the aboral-oral axis of the cnidarians. However, unlike in cnidarians, extensive morphogenetic movements of the tissue during vertebrate gastrulation change the axial position of the cells: while the closing blastopore becomes the posterior end, early involuting cells of the dorsal blastopore lip have a dorsoanterior fate. Hence, it appears that the oral-aboral axis of cnidarians more likely corresponds to the vegetal-animal axis of vertebrates.

The dorsal-ventral (D-V) axis of bilaterians is established through the conserved functions of the signaling factor BMP2/4 (Dpp in Drosophila) together with the secreted BMP antagonist Chordin (Short gastrulation in Drosophila). Studying these genes in cnidarians has helped us understand the evolutionary history of the D-V axis. Components of the BMP pathway are expressed during embryogenesis in the anthozoans Nematostella and Acropora (Technau et al., 2005). Strikingly, in Acropora the bmp2/4 homolog is asymmetrically expressed (Hayward et al., 2002). Subsequently, it was found that bmp2/4, its co-factor bmp5-8, the BMP-like ligand gdf5, the antagonists chordin and gremlin1, as well as several other genes, such as most of the Hox genes, are expressed asymmetrically with respect to the oral-aboral axis in Nematostella (Fig. 6) (Finnerty et al., 2004 Hayward et al., 2002 Matus et al., 2006a Matus et al., 2006b Rentzsch et al., 2006). These findings demonstrate the existence of a molecularly defined second body axis, perpendicular to the oral-aboral body axis, called the directive axis. Surprisingly, in Nematostella bmp2/4 and chordin do not form opposing gradients of expression as they do in vertebrates or flies but instead are expressed on the same side after initially being expressed in a radial pattern around the blastopore (Rentzsch et al., 2006). Recent findings suggest that BMP and chordin function in a negative-feedback loop (Fig. 6H), indicating that BMP signaling is required for symmetry breaking to occur (Saina et al., 2009). It is at present unclear what the consequences of the molecular asymmetry of BMP signaling in anthozoans is, but during metamorphosis into the primary polyp, bmp2/4 expression becomes localized in all eight mesenteries,

Box 2. Experimental analysis in cnidarians

Manipulations of tissues and cells in polyps and embryos

Transplantation experiments (Browne, 1909), in which a piece of tissue was grafted laterally onto a host polyp, revealed the involvement of two developmental gradients in Hydra head formation: a head activation gradient, i.e. the capacity of the graft to induce secondary head formation dependent on its axial origin and the head inhibition gradient, i.e. the gradient of suppression of secondary head formation dependent on the distance from the host head (MacWilliams, 1983a MacWilliams, 1983b). Numerous variations on these classical transplantations have been carried out (MacWilliams, 1983a, MacWilliams, 1983b Broun and Bode, 2002 Gee et al., 2010), including recombination of tissue layers (Schmid and Tardent, 1984 Takano and Sugiyama, 1984), removal and transplantation of interstitial cells (Campbell, 1976 Heimfeld and Bode, 1984) and the dissociation and reaggregation of Hydra cells (Gierer et al., 1972 Technau et al., 2000). Grafting, dissociation and separation of blastomeres and lineage tracing have also been successfully performed in cnidarian embryos (Freeman, 1990 Fritzenwanker et al., 2007 Kraus et al., 2007 Lee et al., 2007 Momose and Schmid, 2006).

Cell cycle analysis

Labeling of S-phase cells with bromodeoxyuridine or 3 H-thymidine has been used to study proliferation in cnidarians and has revealed that, in at least some cnidarians, cells apparently lack a G1 phase (Campbell and David, 1974 David and Campbell, 1972 David and Gierer, 1974 Plickert et al., 1988).

Use of small molecules to study cnidarian development

Cnidarian polyps and embryos are permeable to small molecules that perturb signaling pathways. The GSK3β inhibitor alsterpaullone was used to show that the head organizer in Hydra functions through the canonical Wnt pathway (Broun et al., 2005). The Wnt pathway has also been manipulated by diacylglycerol and LiCl (Hassel and Bieller, 1996 Muller, 1990). Furthermore, chemical inhibitors of the fibroblast growth factor (FGF) receptor (SU5421) and of the mitogen-activated protein kinase kinase MEK (UO129) have been successfully applied during Nematostella embryonic and larval development (Rentzsch et al., 2008).

where it could regulate the differentiation of the retractor muscles (Finnerty et al., 2004 Saina and Technau, 2009). By contrast, in Hydra, in which no morphological asymmetry is detectable, chordin expression is radial in the adult polyp, whereas it is dynamically expressed during budding and regeneration. This suggests that the symmetry break caused by BMP signaling was either lost during evolution or reverted to a radial pattern in the polyp stage of Hydra, leading to a secondary radialization of the body plan (Rentzsch et al., 2007).

Chordin is an important component of the Spemann-Mangold organizer (see Glossary, Box 1) and, therefore, the expression of chordin and Wnt genes around the cnidarian blastopore suggests that the cnidarian and bilaterian organizers are homologous. Accordingly, in division experiments with Nematostella embryos, only the oral half can regenerate a normal polyp (Fritzenwanker et al., 2007 Lee et al., 2007). Furthermore, transplantation of part of the Nematostella blastopore lip from an early gastrula to an aboral position induces the outgrowth of a second oral-aboral axis (Kraus et al., 2007), indicating that the cnidarian blastopore (or part of it) is homologous to the blastoporal organizer of vertebrates. As first reported in 1909, organizer activity is also present at the oral end of the Hydra polyp, at the hypostome, which directly develops from the embryonic blastopore (Browne, 1909). Wnt signaling is crucial for the organizing activity of the hypostome, as upregulation of the canonical Wnt pathway in Hydra results in ectopic head formation in the body column (Broun and Bode, 2002 Broun et al., 2005 Gee et al., 2010).

Transgenic cnidarians. (A,B) A transgenic colony of the marine hydrozoan Hydractinia echinata, driving enhanced green fluorescent protein (eGFP, green) under the control of an actin promoter (act::GFP) in all cells. Dark-field (A) and fluorescent (B) images are shown. (C-E) Transgenic Hydra, with the oral end up. (C) A somatic patch of transgenic ectodermal epithelial cells expressing eGFP under the control of an actin promoter, demonstrating normal axial tissue displacement with growth. (D) Somatic first generation transgenic line expressing act::GFP only in the interstitial cell lineage and its derivatives as a result of late integration after segregation of the stem cell lineage. (E) Transgenic Hydra expressing an actin promoter-driven DsRed2 transgene (act::dsRed, red) in the ectoderm. (F-H) Transgenic Nematostella. (F) Transgenic F1 primary polyp expressing mCherry (red) under the control of a muscle-specific promoter (MyHC::mCherry). (G) Cryo-cross section through the mesentery of an adult polyp showing retractor muscle-specific transgene expression (red) and nuclei staining (DAPI, blue). (H) Confocal longitudinal section of a mesentery of a double-transgenic line expressing a neuron-specific transgene (neuract::GFP, green) and a marker of transgenic retractor muscles (MyHC::mCherry, red) showing close association (merge in yellow) of neurons with muscle cells. Images courtesy of Günter Plickert (A,B), Thomas C. Bosch (C,D), Catherine Dana and R.E.S. (E) and E. Renfer and U.T. (G,H). Image in F reproduced with permission (Renfer et al., 2010). Scale bars: 2 mm in A 500 μm in C-E 200 μm in F 250 μm in G 100 μm in H.

Transgenic cnidarians. (A,B) A transgenic colony of the marine hydrozoan Hydractinia echinata, driving enhanced green fluorescent protein (eGFP, green) under the control of an actin promoter (act::GFP) in all cells. Dark-field (A) and fluorescent (B) images are shown. (C-E) Transgenic Hydra, with the oral end up. (C) A somatic patch of transgenic ectodermal epithelial cells expressing eGFP under the control of an actin promoter, demonstrating normal axial tissue displacement with growth. (D) Somatic first generation transgenic line expressing act::GFP only in the interstitial cell lineage and its derivatives as a result of late integration after segregation of the stem cell lineage. (E) Transgenic Hydra expressing an actin promoter-driven DsRed2 transgene (act::dsRed, red) in the ectoderm. (F-H) Transgenic Nematostella. (F) Transgenic F1 primary polyp expressing mCherry (red) under the control of a muscle-specific promoter (MyHC::mCherry). (G) Cryo-cross section through the mesentery of an adult polyp showing retractor muscle-specific transgene expression (red) and nuclei staining (DAPI, blue). (H) Confocal longitudinal section of a mesentery of a double-transgenic line expressing a neuron-specific transgene (neuract::GFP, green) and a marker of transgenic retractor muscles (MyHC::mCherry, red) showing close association (merge in yellow) of neurons with muscle cells. Images courtesy of Günter Plickert (A,B), Thomas C. Bosch (C,D), Catherine Dana and R.E.S. (E) and E. Renfer and U.T. (G,H). Image in F reproduced with permission (Renfer et al., 2010). Scale bars: 2 mm in A 500 μm in C-E 200 μm in F 250 μm in G 100 μm in H.

In summary, BMPs and chordin (or other BMP-binding molecules) are components of an ancient molecular system used to generate axial asymmetries. Since the morphological consequences of the deployment of this system in cnidarians are drastically different from those in bilaterians, it is premature to homologize the cnidarian directive axis with the D-V axis of bilaterians. Nonetheless, it is clear that the common ancestor of cnidarians and bilaterians used this signaling system for axial differentiation.

Can cnidarians inform us about the evolution of the mesoderm?

Cnidarians, being diploblasts, lack the third germ layer, the mesoderm. To trace the evolutionary origin of the mesoderm, researchers have searched for cnidarian homologs of genes involved in bilaterian mesoderm formation. Most of these genes encode transcription factors, such as the bHLH protein Twist, the zinc-finger protein Snail, the T-box factor Brachyury, myocyte enhancer factor 2 (Mef2) and the HMG protein Forkhead/FoxA, and virtually all of them are present in cnidarians and show differential expression during embryogenesis or later developmental processes. Interestingly, nearly all of these genes appear to be expressed at the blastopore (or the hypostome) and in all, or part, of the endoderm (Fritzenwanker et al., 2004 Hayward et al., 2004 Martindale et al., 2004 Matus et al., 2006b Scholz and Technau, 2003 Spring et al., 2002 Spring et al., 2000 Technau and Bode, 1999 Technau and Scholz, 2003). This suggests that mesoderm might have arisen from endomesoderm (see Glossary, Box 1) in the common ancestor of bilaterians by an altered combination of interactions between these developmental regulators in fact, Hydra Brachyury can induce mesoderm in Xenopus (Marcellini et al., 2003), suggesting that it is not the gene but rather the regulatory context that has evolved.

Since gastrulation is tightly linked to germ layer formation, researchers have also begun to investigate the molecular basis of gastrulation in cnidarians (Fritzenwanker et al., 2004 Kumburegama et al., 2011 Magie et al., 2007). Interestingly, virtually all possible modes of gastrulation (invagination, immigration, epiboly, delamination) occur in cnidarians (Tardent, 1978). With the advent of transgenic technology, it should be possible to follow individual labeled cells in a cnidarian embryo and to monitor their morphogenetic behavior during gastrulation in normal and experimentally manipulated embryos, so as to provide insights into the evolutionary basis of gastrulation movements and their molecular underpinnings.

Do the stem cells found in cnidarians share features with vertebrate stem cells?

Interest in stem cells has increased greatly recently owing to their therapeutic potential. However, because most studies have concentrated on vertebrate models we still have a lot to learn regarding the evolution of stem cells. Studies in cnidarians, particularly Hydra and other hydrozoans, are especially relevant to our understanding of stem cell evolution. Hydra has three cell lineages, which are all self-renewing and maintained by stem cells. The two epithelial cell lineages (ectodermal and endodermal) are maintained by division of cells in the body column. Thus, the differentiated epithelial cells of the body column also serve as stem cells. The interstitial cell lineage of Hydra consists of a multipotent stem cell population that gives rise to nerves, secretory cells, nematocytes and germ cells. Initial attempts to determine the evolutionary relationship between cnidarian and vertebrate stem cells involved searching sequenced cnidarian genomes and EST datasets for homologs of the four pluripotency genes that are known to be expressed in vertebrate stem cells (Klf4, Oct4, Sox2 and Nanog). Clear homologs of these genes have not been identified in the Nematostella or Hydra genome (Chapman et al., 2010), suggesting that either the role of these key genes is performed by related genes or, alternatively, that the circuitry for producing stem cells evolved independently in cnidarians and vertebrates. Support for the latter scenario comes from observations suggesting that the interstitial cell lineage is only present in hydrozoans. Identification of the genes that maintain ‘stemness’ in Hydra and other hydrozoans is an important goal for understanding whether cnidarian and vertebrate stem cells share any evolutionary history.

Symmetry break and asymmetric expression of BMP-like genes and BMP antagonists in Nematostella embryos. (A,B) Early gastrula stage (oral view) showing radial expression of a BMP antagonist, the Nematostella homolog chordin (chd, A), and of the Nematostella BMP2 homolog dpp (B). (C) Double in situ hybridization of chordin and dpp showing that during the mid-gastrula stage, a symmetry break occurs and both genes become expressed on the same side of the blastopore. (D,E) During the planula stage, expression of chordin remains lateral to the blastopore (D), whereas dpp is largely expressed in an endodermal stripe and in a spot at the border of the blastopore (E), on the side of chordin expression. (F) Double in situ hybridization of chordin and dpp in a planula larva showing that both genes remain expressed asymmetrically, on the same side, but segregate with respect to ectoderm and endoderm. Asterisks mark the blastopore. Scale bar: 100 μm. (G) Schematic of the planula stage illustrating the asymmetric expression of chordin and dpp on one side, and of gdf5-like, a member of the BMP family, and of gremlin, a BMP antagonist, on the opposite side. Note that a number of other genes (not shown for clarity) are also expressed asymmetrically, indicative of a directive axis. (H) Double negative-feedback loop between Dpp and Chordin as suggested by morpholino-mediated gene knockdown experiments (Saina et al., 2009). Images in A-G are reproduced with permission (Rentzsch et al., 2006).

Symmetry break and asymmetric expression of BMP-like genes and BMP antagonists in Nematostella embryos. (A,B) Early gastrula stage (oral view) showing radial expression of a BMP antagonist, the Nematostella homolog chordin (chd, A), and of the Nematostella BMP2 homolog dpp (B). (C) Double in situ hybridization of chordin and dpp showing that during the mid-gastrula stage, a symmetry break occurs and both genes become expressed on the same side of the blastopore. (D,E) During the planula stage, expression of chordin remains lateral to the blastopore (D), whereas dpp is largely expressed in an endodermal stripe and in a spot at the border of the blastopore (E), on the side of chordin expression. (F) Double in situ hybridization of chordin and dpp in a planula larva showing that both genes remain expressed asymmetrically, on the same side, but segregate with respect to ectoderm and endoderm. Asterisks mark the blastopore. Scale bar: 100 μm. (G) Schematic of the planula stage illustrating the asymmetric expression of chordin and dpp on one side, and of gdf5-like, a member of the BMP family, and of gremlin, a BMP antagonist, on the opposite side. Note that a number of other genes (not shown for clarity) are also expressed asymmetrically, indicative of a directive axis. (H) Double negative-feedback loop between Dpp and Chordin as suggested by morpholino-mediated gene knockdown experiments (Saina et al., 2009). Images in A-G are reproduced with permission (Rentzsch et al., 2006).


E. Yagmur Erten and Pieter van den Berg contributed equally to this work.

Affiliations

Theoretical Research in Evolutionary Life Sciences, Groningen Institute for Evolutionary Life Sciences, University of Groningen, PO Box 11103, 9700 CC, Groningen, The Netherlands

E. Yagmur Erten, Pieter van den Berg & Franz J. Weissing

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

Laboratory of Socioecology and Social Evolution, Department of Biology, KU Leuven, Naamsestraat 59—bus 2466, 3000, Leuven, Belgium

Netherlands Institute for Advanced Study in the Humanities and Social Science (NIAS-KNAW), PO Box 10855, 1001 EW, Amsterdam, The Netherlands


In Human Evolution, Changes in Skin’s Barrier Set Northern Europeans Apart

The popular idea that Northern Europeans developed light skin to absorb more UV light so they could make more vitamin D – vital for healthy bones and immune function – is questioned by UC San Francisco researchers in a new study published online in the journal Evolutionary Biology.

Ramping up the skin’s capacity to capture UV light to make vitamin D is indeed important, according to a team led by Peter Elias, MD, a UCSF professor of dermatology. However, Elias and colleagues concluded in their study that changes in the skin’s function as a barrier to the elements made a greater contribution than alterations in skin pigment in the ability of Northern Europeans to make vitamin D.

Elias’ team concluded that genetic mutations compromising the skin’s ability to serve as a barrier allowed fair-skinned Northern Europeans to populate latitudes where too little ultraviolet B (UVB) light for vitamin D production penetrates the atmosphere.

Among scientists studying human evolution, it has been almost universally assumed that the need to make more vitamin D at Northern latitudes drove genetic mutations that reduce production of the pigment melanin, the main determinant of skin tone, according to Elias.

“At the higher latitudes of Great Britain, Scandinavia and the Baltic States, as well as Northern Germany and France, very little UVB light reaches the Earth, and it’s the key wavelength required by the skin for vitamin D generation,” Elias said.

“While it seems logical that the loss of the pigment melanin would serve as a compensatory mechanism, allowing for more irradiation of the skin surface and therefore more vitamin D production, this hypothesis is flawed for many reasons,” he continued. “For example, recent studies show that dark-skinned humans make vitamin D after sun exposure as efficiently as lightly-pigmented humans, and osteoporosis – which can be a sign of vitamin D deficiency – is less common, rather than more common, in darkly-pigmented humans.”

Furthermore, evidence for a south to north gradient in the prevalence of melanin mutations is weaker than for this alternative explanation explored by Elias and colleagues.

In earlier research, Elias began studying the role of skin as a barrier to water loss. He recently has focused on a specific skin-barrier protein called filaggrin, which is broken down into a molecule called urocanic acid – the most potent absorber of UVB light in the skin, according to Elias. “It’s certainly more important than melanin in lightly-pigmented skin,” he said.

In their new study, the researchers identified a strikingly higher prevalence of inborn mutations in the filaggrin gene among Northern European populations. Up to 10 percent of normal individuals carried mutations in the filaggrin gene in these northern nations, in contrast to much lower mutation rates in southern European, Asian and African populations.

Moreover, higher filaggrin mutation rates, which result in a loss of urocanic acid, correlated with higher vitamin D levels in the blood. Latitude-dependent variations in melanin genes are not similarly associated with vitamin D levels, according to Elias. This evidence suggests that changes in the skin barrier played a role in Northern European’s evolutionary adaptation to Northern latitudes, the study concluded.

Yet, there was an evolutionary tradeoff for these barrier-weakening filaggrin mutations, Elias said. Mutation bearers have a tendency for very dry skin, and are vulnerable to atopic dermatitis, asthma and food allergies. But these diseases have appeared only recently, and did not become a problem until humans began to live in densely populated urban environments, Elias said.

The Elias lab has shown that pigmented skin provides a better skin barrier, which he says was critically important for protection against dehydration and infections among ancestral humans living in sub-Saharan Africa. But the need for pigment to provide this extra protection waned as modern human populations migrated northward over the past 60,000 years or so, Elias said, while the need to absorb UVB light became greater, particularly for those humans who migrated to the far North behind retreating glaciers less than 10,000 years ago.

The data from the new study do not explain why Northern Europeans lost melanin. If the need to make more vitamin D did not drive pigment loss, what did? Elias speculates that, “Once human populations migrated northward, away from the tropical onslaught of UVB, pigment was gradually lost in service of metabolic conservation. The body will not waste precious energy and proteins to make proteins that it no longer needs.”

For the Evolutionary Biology study, labeled a “synthesis paper” by the journal, Elias and co-author Jacob P. Thyssen, MD, a professor at the University of Copenhagen, mapped the mutation data and measured the correlations with blood levels of vitamin D. Labs throughout the world identified the mutations. Daniel Bikle, MD, PhD, a UCSF professor of medicine, provided expertise on vitamin D metabolism.

The research was funded by the San Francisco Veterans Affairs Medical Center, the Department of Defense, the National Institutes of Health, and by a Lundbeck Foundation grant.

UCSF is the nation’s leading university exclusively focused on health. Now celebrating the 150th anniversary of its founding as a medical college, UCSF is dedicated to transforming health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy a graduate division with world-renowned programs in the biological sciences, a preeminent biomedical research enterprise and two top-tier hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco.


Evolutionary Biology of Harvestmen (Arachnida, Opiliones)

Opiliones are one of the largest arachnid orders, with more than 6,500 species in 50 families. Many of these families have been erected or reorganized in the last few years since the publication of The Biology of Opiliones. Recent years have also seen an explosion in phylogenetic work on Opiliones, as well as in studies using Opiliones as test cases to address biogeographic and evolutionary questions more broadly. Accelerated activity in the study of Opiliones evolution has been facilitated by the discovery of several key fossils, including the oldest known Opiliones fossil, which represents a new, extinct suborder. Study of the group's biology has also benefited from rapid accrual of genomic resources, particularly with respect to transcriptomes and functional genetic tools. The rapid emergence and utility of Phalangium opilio as a model for evolutionary developmental biology of arthropods serve as demonstrative evidence of a new area of study in Opiliones biology, made possible through transcriptomic data.


Watch the video: ΠΕΡΑ ΑΠΟ ΤΑ ΟΡΙΑ, ΨΑΧΝΟΝΤΑΣ ΤΙΣ ΧΑΜΕΝΕΣ ΨΥΧΕΣ, ΔΗΜΙΟΥΡΓΩΝΤΑΣ ΤΟ ΠΑΡΟΝ ΚΑΙ ΤΟ ΜΕΛΛΟΝ (November 2022).