Those viral Evolutionary Biology notes. A late confession.

Time for late confessions. This story dates back to the 2000s, and it is about free diffusion of knowledge, internet, evolution, an angry academic and a monster (I mean “another monster”, distinct from the angry academic). It was the 2007, and I was hardly trying to find a way out from my bachelor degree. At the time, I had to do the exam of Evolutionary Zoology, which classes were held by Professor Raffaele Scopelliti at the Dept. of Zoology of the Sapienza University. I was never the one for sitting in a classroom, and skipped as much classes as I could. It was permitted, and the schedule was so terribly organised that was really hard to embed your commitments. This was the life at the Italian university during the 2000s. Courses overlapped, the thesis lab-work could take all your day, and the best you could do to survive was to choose a comfortable library to sit down and study for extra-session exams. I was told that things turned slightly better in the last years, but then this confusion matched a lot with my natural “too cool for school” attitude, taking me far from lessons very often. During the spring of 2007 I had few time to study Evolutionary Zoology, I did not attend the course, and needed a solution. Usually, the solution in these cases was to grab someone else’s notes, and one day my friend Amro showed up with a copybook full of notes from the Prof. Scopelliti’s lessons. The notes belonged to a girl I never knew the name. Amro had to return the notebook to her soon, and suggested me to photocopy all the pages.

I started to rewrite the notes on Google Docs, organising them as a real text book, with chapters, sections, headings and all the rest. It was tough sometimes, since the photocopies of a handwritten text are hard to read, and often it turned to be a matter of free interpretation. Also, from time to time I found my activity quite boring, and since I am a huge fucker, I started to thread jokes and foul language in my writing. As said, it was the 2007, and that story of the Flying Spaghetti monster was just starting to spread in Europe. As I started to rewrite the lesson that swiftly (and of course critically) described the alternative evolutionary theories, from Lamarck to Creationism, I had the brilliant idea to insert a description of the Flying Spaghetti Monster theory, taking care to mention that was a hilarious fact.

The exam day had come, and the result was strikingly good: 30 out of 30, the best mark you can get in the wierd Italian evaluation scale. The real problems arose later. I was very active in promoting things such as open science and the free distribution of knowledge at the time, and the best I could do in my own little was to publish my notes on a biology students unofficial forum we had (there was no Facebook yet, oldie me). The response was good. Students appreciated the initiative, the link was diffusing very quickly, and people was quite happy to read notes where some joke could eventually pop up from time to time and kill the bore. Unfortunately, a couple of months later, I spotted a post on the message board of the official website of the Faculty of Biology. It was authored by Raffaele Scopelliti, and the title was “Warning on Evolutionary Zoology fake-notes“.

I opened the message and the body was imperative and threatening. I don’t remember the exact words, but it sounded like this:

Dear Students, someone has published some very inaccurate and awkwardly incorrect Evolutionary Zoology notes that are referred to my lessons. I gave no permission to publish them. I urge you to quit studying from them. I don’t know the author of this brilliant work, but I swear that I will find this guy.

I gave it no much importance. My exam was done and registered, and I was far and safe from professor’s anger. But later on, I was explained how he came across my notes. First, some transcription errors spread out, becoming very popular among the students, just like the Haeckel’s Biogenetic Law that was written as “Haeckel’s Progenetic Law” because of a misreading of mine. Also, it seemed that anyone really liked the story of the Flying Spaghetti Monster to the point that many people reported it during the exam. In Italy the most of the exams consist in oral interviews, and those present told me that professor Scopelliti, after having heard the story of the monster for the umpteenth time, literally started to yell “who told you about this damned monster”?

The fact itself is funny, expecially if you consider the very formal italian academic environment. I admit that my story is of small interest, but I guess we could learn something from it. When I published online my document, I carefully and repeatedly warned the people that they had to check everything on it, that those pages represented just a raw product, and that it was full of inaccurancies to be corrected. Actually, this story taught me something on the way university students do their work. The most of the times people is so focused on learning as most notions they can, without giving the due consideration to the critical review. At the time, it made me think. I knew I wasn’t any better than the most of the people, and the same lack of criticism that gets students to talk about flying monsters in an Evolution exam could have affected me as well. Also, it was the first time when I experienced the danger of freely diffusing information on the internet, and some long reflections could be made on this point too.

But this is mostly a post for a late confession. Dear prof. Scopelliti, I have no idea whether you will ever read these lines or not, but I guess that you might remember this story. I just want you to know that it was me, that I am still trying to make my way in Evolutionary Biology, and no. I don’t apologise for what I did.

My notes were still better than the nothing you shared as course materials.


Applying phylogenetics and bioinformatics to NF-kB studies

To anyone having to do something with immunity studies, the nuclear factor kappa-light-chain-enhancer of activated B cells, will sound really familiar. The NF-kB is a protein complex deputed to initiate the transcriptional response to external stimuli, such as stress, citokines, antigens, bacteria, free radicals or UV light irradiation. Expressed in active B cells, it is the protagonist of the immune response at molecular level.

For quite a long time, its evolutionary characterization has been rather neglected, since no homologous sequence is found. Actually, I often happen to realize that biomedical studies tend to keep quite far from evolutionary approach. Biomedicine is about to understand processes happening here and now, and it often aims to quickly find a reliable therapeutic approach for the disease of subject. So many factors to study, so little time. This shifts biomedical studies away from the influence of evolutionary biology. A real pity, as Catriona MacCallum  pointed out on PLoS Biology in 2007, since the contribution of evolutionary biology to biomedicine has a big, almost unexplored potential.

Recently, NF-kB and NF-kB-like proteins have been discovered in “basal” marine animals and non-metazoans, allowing the study of the early evolution of this nuclear complex of extraordinary importance for human health. John R. Finnerty and Thomas D. Gilmore from the University of Boston published an interesting paper on this topic just a few months ago, and I dare to introduce it here for two main reasons.

Beyond the clear scientific interest of their work, representing one of the few and really valuable evolutionary approaches to an all-biomedical subject, and highlighting deep conservation and repeated instances of parallel evolution in the sequence and structure of NF-κB in distant animal groups, which suggest that important functional constraints limit the evolution of this protein, it also provides an explanation of how to easily apply phylogenetic and bioinformatic approaches even without a previous hard training.

The authors run on the double track of reporting a scientific result, and introducing the reader to some simple (but still effective) computational tools that more or less anyone may use to implement phylogenetics in his/her work, rendering Methods for Analyzing the Evolutionary Relationship of NF-κB Proteins Using Free, Web-Driven Bioinformatics and Phylogenetic Tools a very interesting reading for both bionformaticians who need to communicate with experimentalists, and people working with NF-kB.

The article is part of the methodological book NF-kappaB. Methods and Protocols edited by Michael J. May and published by Springer Protocols.

Genome3D organisation and evolution. Going beyond flat files.

The genome is a real thing, and this is something we strongly need to keep in mind. The development of bioinformatics has brought us to make a very important, but still bold simplification. A strong focus on sequences, and the information they bear, allowed us to understand how genes determine the structure and function of proteins, and is driving the work of anyone focusing on the interpretation of non-coding elements, in the restless seek of what someone calls the regulatory code. Basically, we took the object shown in the picture above, and transformed it in flat files that underwent to the application of information theory. Beyond the obvious and widely discussed advantages, this approach may have the potential to be misleading. The genome is a physical body, with its physical and chemical features. And as epigenetics is putting the protein- DNA interaction under the spotlight, many studies are underlying that the functioning, the regulation, and thus the evolution of the genome need to be explored considering the genome as what it really is: a complex three-dimensional object.

I really enjoyed the read of a paper dating back to the 2011, authored by Johan H. Gibcus and Job Dekker from the University of Massachusetts. Entitled The Hierarchy of the 3D Genome, the article provides an effective point of view on how radically the DNA folding affects the genome regulation. Recent innovation in probing interphase chromatin folding are in fact providing new insights into the spatial organisation of genomes and its role in gene regulation. In fact, a paper by Marc M. Renom (CNAG- Barcelona) on PlOS, that is aimed at explaining the state of the art of computational methods for genome folding analysis, argues that after the advent of fluorescent in situ hybridisation imaging and chromosome conformation capture methods, the availability of experimental data on genome three-dimensional organisation has dramatically increased. This information has been recently made available in the 3D Genome Database (3DGD), that is the result of the work of a Chinese team, and gathers the Hi-C chromatin conformation capture data of four species (human, mouse, drosophila and yeast).

Of course, many results proving a role of genome folding in gene regulation and phenotype determination are leaping off. As already discussed in this blog, researchers from McGill University in Canada have proven that leukaemia types can be classified with chromatin conformation data. Under an evolutionary point of view, we could have a look to this paper published on Nature in 2012, in which specific chromatin- interaction domains, defined as topological domains, are found to be conserved over the time and in different species.

Beyond any consideration, and further discussion, we could assume that a change in the approach we adopt in genome studies is needed. These findings suggest that a level of major complexity affects genome regulation, and this cannot definitely be ignored. In evolution, we should ask how the chromatin structures have established over the years, and understand their meaning in phenotype and adaptation. Of particular interest, would be the role of non-coding sequences, the so-called junk (and not so) junk DNA, that has been found in many topological domains and may have a role. Ultimately, as we assign a function of three dimensional structure for DNA, as we did in proteins, we should investigate the relationship between the sequence and the structure, and the information exchange between proteins and DNA in protein binding. It seems that not everything is clear about the nature of the information in biological macromolecules, but that’s all but a novelty.

Information and intelligence: let's meet the Smart Slime

As we talk about information in biology, mind goes through DNA and protein sequences, on the tracks of what we have learned to call “bioinformatics”, along with a fair amount of algorithms, open source methods, coding hacks, genome assemblies, libraries and bugs. Luckily, Biology is much more complex and beautiful than mere green strings, and information in biological systems flows at different scales, involving several processes. And if we can call communication the information transfer between two entities, the capability of a system to learn from environmental information in order to improve its adaptive response, could be fairly (even if a bit boldly) defined as intelligence.

What is intelligence? Where does it rely? How can we measure it? Great questions, that would generate a huge discussion. Far bigger than this small blog. Anyway, I guess that the best option here is to start talking about something very simple. A slimy mold, for instance.

Physarum polycephalum is known as the many-headed slime and, as reported on Wikipedia is a slime mold that inhabits shady, cool, moist areas, such as decaying leaves and logs. Like slime molds in general, it is sensitive to light; in particular, light can repel the slime mold and be a factor in triggering spore growth. The really amazing fact about this slimy fellow, is that many investigations have proved him as capable of the capability to solve complex problems.

The video I am sharing above these lines, is a TED talk held by Heather Barnett. Designer working with bio-materials and artist, Heather Barnett creates art with slime mold, and shows us how much amazing this organism can be.

With a simple, but very effective cell-based information processing system,  P. polycepalum has been proved to quickly find the best path to food through a maze, way faster than me when I had to find the best path to train station from my home through Gràcia. More, the video shows how the mold reconstructed in scale the Tokyo suburban rail system, proving its capability to solve complex problems and tasks.

Of course, to anyone studying cognitive processes at a  molecular level, this organism provides an excellent model, but we may also fetch some good idea for evolutionary biology too. The best way to thread into this is a visit to Heather Barnett’s website, that is provided with many video (there is a youtube channel too), information and references.


The role of mathematical modelling in evolutionary biology.

The role of mathematical modelling in evolutionary biology is pretty questioned, although its integral role in studies on evolution. Differently from other scientific disciplines, such as Physics or Chemistry, Biology was born as a descriptive science, and the affirmation of mathematics as an effective and indispensable part of investigation is still to be fully accomplished. In evolutionary research, an important role of mathematics is to provide a “proof-of-concept” test of verbal explanations, paralleling the way in which empirical data are used to test hypotheses.

Whereas the connection between empirical analyses and theoretical modelling is straightforward in some cases, such as the construction of likelihood functions for parameter inference and model choice, empiricists may not appreciate the importance of highly abstract models, which might not provide immediately testable predictions. Probably, skepticism stems from some misconceptions and misunderstandings about mathematical modelling, and a clarification about its role may ease the communication between experimentalists and theoretical biologists.

Some evolutionary biologists from the USA point this out in a very clear paper, published some days ago on PLOS Biology, and first-authored by Maria Servedio from the University of North Carolina. The parallels between empirical experimental techniques and proof-of-concept modeling in the scientific process are explained in the following flowchart.

As shown, the proof-of-concept models are best suited to test the logical correctness of verbal hypotheses, such as the effectivity certain assumptions have to lead to certain prediction. Hypotheses which assumptions are most commonly met in Nature, are instead argued to be possibly addressed by empirical approaches only.

Discussion on most common misunderstandings is centred around three main points.

The authors first argue that the main misunderstandings, in matter of mathematical modelling, happen as theoreticians are asked how they might test their proof-of- concept models empirically. The models are discussed to be themselves tests of validity of verbal assumptions, and their outcome can thus determine whether a verbal model is valid or defective.

Second, this does not mean that proof-of-concept models do not need to interact with empirical work. Actually, in most of cases, quite the contrary is true. Many vital links between theory and natural systems can be found in assumption stage, prediction stage and even in discussion stage, when empirical results are threaded into a broader conceptual framework.

Third, authors point out that a discordance between theoretical predictions and empirical data may be a great point of interest, giving to both theoreticians and experimentalists the opportunity to appreciate underrated phenomena, or to reconsider the assumptions and empirical procedures.

Despite this paper discusses in detail the role of theoretical modelling in evolutionary biology, we should take our time to reflect, in general terms, on the relationship between experimental work and mathematical modelling. I am very next to write about the criticism that is investing some of the most common algorithms for NGS data analysis, because I have the feeling that the search of proper mathematical modelling algorithms will be one of bioinformaticians’ main occupation in coming years. This article serves thus as a fair example, even if not directly applicable to all the fields of life sciences, of how the relationship between empirical and mathematical work should be properly interpreted.

How reductionism brought James Watson into racism and insulation.

James Watson is seriously facing the risk to go broke. After his comments on the linkage between race and intelligence in 2007, when he claimed that Africans were genetically less intelligent than Caucasians, the American molecular biology pioneer suddenly ran into isolation, drawing the contempt of public opinion and academics. Now, his budget is dangerously low, and he decided to auction Nobel Prize medal to fuel his finances and to make a couple of donations. Evidently, and despite his advanced age, the need to clean up his public profile is still very strong. As I have read this on The Guardian, my mind went back to 2007, when I was an undergraduate staring in disconcert at such unbelievable comments by the man whose discoveries caused me, and thousands students like me, to join biology.

As extensively explained on The Independent, Watson proposed that the IQ tests, conducted on Afro- Americans, confirmed a significant racial divide in intelligence, and discussed some connotations in welfare policies. He claimed genes responsible for human intelligence determination could be found within a decade, to provide an experimental support to his statements.

Despite controversy understandably focused on racism at the time, I have always found quite curious that intelligence could be “written in our genes”. Before any consideration on the social implications, we should reflect about the scientific bases of what Watson says: is DNA able to determine how smart we are? During the past decade, as the sequencing capability grew exponentially, the belief that any possible answer in biology could be found in the DNA became dominant. Enthusiasts, and molecular biology advisors, eagerly celebrated the golden age of genomics, proposing a bright future made up of genome wide- screenings, personalised medicine, and other disturbing GATTACA- like scenarios.

Everyone seemed pretty sure that any phenotype could find his direct counterpart in the genetic code, firmly trusting in the neo- Darwinian commandment claiming the existence of a simple relationship between genotype and phenotype. According to this view, even a very complex and hard- to be determined phenotypic trait as intelligence must be the effect of some gene. Everything is thus very easy: one day we will discover the genes controlling intelligence, creativity, love and even football addiction. You don’t need a degree to understand how much improbable is this. Luckily, the application of complex systems theory to molecular biology and evolution is telling a different story, and the current challenge is to understand how the phenotype is determined by independent contributions at genetic, protein, cell and macroscopic level.

The very first mistake James Watson did was not his racist outbursts, but his giving in to the lure of reductionism. Intelligence is the result of complex interactions at neuronal level, and human brain’s huge plasticity is our winning strategy in evolution. Over the years, no convincing proofs of the existence of genes controlling intelligence have been provided, and the main trend in brain research is to focus on brain’s impressive ability to change and improve. Moreover, IQ test are highly controverted, because their ability to predict the potential of a mind is all but demonstrated. The American molecular biologist applied a reductionist approach to a pretty complex matter, by using a very weak indicator, since there are no genes controlling intelligence, and the IQ itself is just pointless.

Watson’s creepy positions are thus the direct consequence of a kind of “genomic delirium of omnipotence”. It confirms that in Science, and in life itself, terrible things may happen if you choose the simplest route, indulging in simple answers to hard questions, and leaning on shallow descriptors of complex phenomena.

Is creationism still compatible with Christian Religion?

One of the very first posts in this blog, was about the “evolution of creationism” in Catholic Church, arguing that the Catholic Church is not anti- Darwinian anymore, but oriented to propose a “peaceful co-existence” between creationism and biological evolution. Divine creation is actually considered a transcendental event, and biological evolution its reflection on the immanent plane. With this very simple deal, Vatican authorities have started a path of reconciliation with Science, that started at the age of John Paul II, and met another important step forward with Pope Francis.

As we read the story of Creation on the Genesis, we risk to believe that God was a wizard holding a wand that can do anything. Not so. He created the beings, and let them evolve according to the internal laws he gave, in order to let them develop and reach their fullness. He gave autonomy to the beings of the universe as he ensured his continuous presence, giving the essence to any reality. Pope Francis I– Speech at the “Pontifical Academy of Sciences”- 2014 (Source: Huffington Post Italia).

Last week pontiff’s public declarations made really clear that this path is accomplished: Catholics support the validity Darwin’s evolution and Big Bang Theory, that are not in contrast with the belief in Jesus Christ and the message of the church. “Being Christians” – says the Pope – “doesn’t mean being naive”, as he argues his point of view on Science- Religion relationship. In front of this historical turn, I just wonder why so many christians are still violently claiming that evolution is the “fruit of the Devil” and thus incompatible with their belief.

The real point is that no one can really claim that the “official christian religion” denies Darwin’s theories for one simple reason: there is not an “official christian religion”. The Lutheran Reform ended up the Church’s esclusive rule on Western Christianism, as previously the Schism did in Eastern Europe and Near East. Over time, many different and independent organizations established, bringing that considerable diversity in cults and Scripture interpretation we can appreciate nowadays. Who is in the right to tell, beyond any doubt, what is in contradiction with christian religion?

Scriptures are always invoked by fundamentalists as the incontestable word of god, and proof of the Creation. No more clues are given when they’re asked to tell what Scriptures they are talking about. Indeed, the historical validity of the Bible is deeply controverted, and the huge number of interpretations can lead to very diverse positions. Many protestant christians accept evolution, that is a very open debate in Orthodox Church as well. Catholic Church is the oldest and the biggest christian church in terms of believers and territorial expansion, and I guess that the guys at the Vatican know a thing or two about theology. Relevantly, the most of current theologists reject the literal interpretation of Bible, in an open contrast with the most radical positions.

This Pope’s stance may result in a deathblow to radical creationists, that are ending up as a minority in the christian movement. It has to be pointed out that a real issue of compatibility between classical creationism and christian beliefs is rising, as the whole christianity is moving towards a more reasonable approach to their religion. Fundamentalism is getting to be relegated

To me, and I guess to the most of the readers, this is not really relevant for my position. I am in Science because I consider rationality as the only mean to investigate nature, I radically adverse religion and catholic church, and I definitely don’t need the papal approval to assume Evolution Theory as valid. Anyways, understanding that the “creationist front” is billing up, and that rationality is appreciated by christians as well, is something I really enjoy. It’s the sign that Science irreversibly imposed a direction to history towards openness, tolerance and reason.