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.


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.


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.

The role of cis-regulatory sequences in Zea mays evolution.

The paper I am going to share today collected my attention because it merges two fundamental topics that are quite a lot undertaken in evolutionary biology: plant genomics and the rule of cis-regulatory elements in evolution. Plant biology provides an excellent framework to perform studies in genomic evolution. Even if the knowledge acquired is applied mostly in agricultural biotechnology,  that is a field that trills me a lot, plants represent a perfect environment to understand general- validity principles in genomic evolution. The role of cis- regulatory elements, and their contribution to organism differentiation, are generally understood to be very relevant, but I sense that this topic is quite neglected and a bit obscure.

Modification of cis regulatory elements to produce differences in gene expression level, localization, and timing is an important mechanism by which organisms evolve divergent adaptations. (Lemmon et al., Plos Genetics, 2014)

That is why I have particularly enjoyed the reading of this brand new paper, authored by Zachary H. Lemmon and co-workers, and developed in a collaboration between the University of Wisconsin and Ithaca University (NY). In plant biology, one of the main points of interest is obviously the process of domestication, and its analysis under a molecular point of view. In this paper, maize domestication is analyzed by a genomic comparison among domesticated  and non domesticated species within the Zea genus.

To examine the differences in gene regulation during maize domestication from its wild progenitor, teosinte, an allele specific expression analysis is performed on pure lineages and hybrids in different trans and cis regulatory regimes. The investigation focuses on three tissues (ear, leaf and stem) from different developmental stages. RNA-seq analysis provide the confirmation of the consistent cis regulatory divergence in genes that are significantly correlated with the ones under selection during domestication and crop improvement. This suggests the important role for cis regulatory elements in maize evolution.

As the authors argue the relevance of this result for plant biology, we can understand that this study highlights the importance of regulatory genome in evolution, and the great potential that plant biology have as framework for evolutionary biology.


Human genetics, gut microbiome and evolution.

I have never made a big secret of my passion for microbiota biology. The interaction between microbial communities and host organism is definitely one of the best topics to take stock of  the amazing complexity of biological systems. In fact, I have already discussed about some possible applications for theoretical biology in this field, and introduced a couple of bioinformatics methods aimed at metagenomics analyses. Today, I return to this topic to report a brand- new amazing paper on Cell, authored by Julia K. Goodrich and co. from the Ithaca University (New York).

How are human genetics and microbiome composition interlinked? This study proposes a strong genetic determination in the abundance of many microbial taxa in human gut microbiota, after an investigation on more than 1,000 fecal samples from 416 twin pairs (homo- and heterozygotes) living in the UK. Intriguingly, “the most heritable taxon, the family Christensenellaceae, formed a co-occurrence network with other heritable Bacteria and with methanogenic Archaea”, and data prove its strong role in the onset of obesity, suggesting new possible therapeutic applications.

As I skip a well- detailed discussion, letting you insight this paper on Cell’s website, I limit to rattle off a couple of considerations on the *theoretical side*. The interplay between gut microbiota and host genome, even if strongly supported in this work, is not a big novelty. Under an evolutionary point of view, the importance of symbiosis in organisms’ life and adaptation, gave rise, in 2008, to the very debated “hologenome theory of evolution“, that propose the “holobiont” (organism + associated microbial communities) as the subject of selection instead of the mere organism.

Actually, I never focus on genomic evolution only, sensing that, if defined as the change of dynamic and replicating complex systems over generations, evolution cannot be properly studied at genomic level only. In host- microbiota interaction, we appreciate a complete mutual dependency between organisms belonging to very different domains. The microbial community behavior, the immune response, the cell-to-cell communication, epigenomic regulation, protein interactions, and the effects of genetic determination found in microbiome studies, indicate a very complex and multi- level process as determinant in any eukaryote- microbial symbiosis. As we get totally aware about the relation between human genetics and microbiome composition, the open questions are still  in which way, and to which extent, host genome can affect microbial communities, and how much the symbiosis influenced adaptation and evolution of higher eukaryotes.

And this explains fairly well why I am so interested in everything about microbioma. Studying the way how microbes live along with animals and plants, makes a perfect framework to tackle questions of general interest in theoretical biology. As in any study, we can recognize an interplay between complex systems at a different organization level, and to understand the evolution, we need to accept complexity as a fact, and try to understand in which extent any level contribute to adaptation and evolution. Though, differently than other fields, I sense that the microbiome constituted a very effective framework to do this.

Tajima's D statistics explained in a 9 minutes lecture.

Tajima’s D is a statistical test used to distinguish between a DNA sequence evolving randomly or neutrally and one evolving under a non- random process, such as directional or balancing selection, demographic expansion or contraction, genetic hitchhiking or introgression. Created by and named after the Japanese evolutionary biologist Fumio Tajima, this test is very useful to reject the null- hipotesis that a given DNA sequence evolved randomly.

More than thousand words, the video I am sharing with you will help to understand how this algorithm works. A short, clear and very effective lecture held by Mohamed Noor, professor at the Duke University that will be really explanatory.