Lately I have been publishing about molecular evolution, i.e. how evolution worked on a molecular level. I try to find the actual path taken in evolution, a step-by-step reconstruction about the events that happened in evolution. I try to unravel these steps by modelling evolution on an engineering paradigm called design-by-contract. This design pattern is used in software development to make a system extensible, flexible and robust, the same requirements that an evolvable system would need. Design-by-contract is based on a modular system that communicates through constant interfaces, I propose in biology recognizable by a conserved function or DNA sequence. One can then deduce from the developmental steps which would constitute the only logical way to build that structure during evolution. Not surprisingly, the developmental steps follow the evolutionary steps. I have substantiated my theory by a number of articles in peer-reviewed journals. 

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de Roos, ADG (2008). Evidence for exon-mediated domain shuffling in the formation of complex eukaryotic genes. pdf

de Roos, ADG (2008). Reverse engineering evolution on the basis of design patterns for complex systems. pdf

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de Roos ADG (2007). Modelling evolution on design-by-contract predicts an origin of life through an abiotic double-stranded RNA world. Biology Direct, 2:12 (pdf)

One of the most intriguing questions in evolution is how life evolved. Further building on my design-by-contract theory, I decided to try to unravel the steps that lead to the formation of the informational carrier double-stranded DNA and the derived catalytic RNA. I first determined the functional interfaces and then derived the logical sequence of events in evolution. The main result was that the double-stranded form with the information-storage capabilities arose first, followed by the single-stranded catalytic form. Not surprisingly, this sequence is the exact sequence we see in developement. The article describes also a way how to arrive to this double-stranded form abiotically and shows how existing functions are maintained during the course of evolution. This principle of functional continuity has been recognized in evolution, but is hardly applied. The difference with mainstream origin-of-life research is that I focus on the engineering part (after all life is an an evolving molecular machine), while others concentrate on the chemistry.

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de Roos ADG (2007). Conserved intron positions in ancient protein modules. Biology Direct 2:7 (pdf)

This article goes on where my other article about introns left. I proposed that exons were the original modules that were concatenated early in evolution to form multimodular proteins and theorized that they could still be found in the form of conserved introns. I used a relational database with intron-exon database and tried to find those ancient exon concatenations, by just comparing splice site sequences between distantly related organism (e.g. plant-animal). I found a set of these ancient introns and studies them. I found that these were characteristic for ancient sequences, but also that they could be specifically found in ancient protein modules. In fact, I porvided evidence that the functional modules were built from smaller exon subunits. Thus, exons did not represent functional modules by themselves, but could ahve functioned as Lego blocks that could be assembled into functional modules. Together with the results I found earlier in which I propose that the ends of exons represented active recombination sequences, this paves the way for scenarios where exons were actively recombined and selected to form a basic set of proteins like phosphatases and kinases involved in early life.

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de Roos ADG (2006). Origin of insect metamorphosis based on design-by-contract: larval stages as an atavism. submitted pdf

I tested my design-by-contract theory not only on early cellular evolution, but also with insect metamorphosis which represent one of the mysteries of evolution and an easy example for non-biologists about the complexity of evolution. Insect evolutionists think that the larval stages (eg caterpillar) was evolved because of the advantages that it would bring regarding food partitioning. I always found this kind of reasoning strange since this can only be an advantage after the completion of the larva and will not be advantageous during its evolution. Moreover, technically, it seems impossible to introduce new developmentla pathways in the middle of the normal devlopemental pathway. Evolutionists never bother about the mechanistic aspects (and thus ignore the fact that life is a molecular machine), but I do and reasoned that the larval stages were developed earlier in evolution than the adult stages. This fits into the developmental pathway of insect devlopement when the larval stages are considered an atavism, an out-of-use body plan so to speak. I once submitted this to a zoological journal, but it was ridiculed (which is strange because there are no mechanistic scenarios decribed that maintain functional continuity) so I decided to just put it on the internet. Read more here. I think this will be continued as well.

 

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de Roos ADG (2006) The origin of the eukaryotic cell based on conservation of existing interfaces. Artif Life. 2006 Fall;12(4):513-23. (pdf)

When I was developing my theory where evolution could be modelled on design-by-contract, I started reading about the origin of the eukaryotic cell. The question is how the nucleus that contains all the DNA is formed in eukaryotic cells. It was thought, based on the (IMO false) premise that the eukaryotic cell evolved from a bacteria-like prokaryote, that the nucleus evolved late in evolution. When you look at all the mechanistic aspects of such a scenario that includes transfer of all the important cellular processes, I concluded that this was impossible. The only feasible way in line with design-by-contract  is that the nucleus always existed as an independent unit and ‘just’ formed an extra layer around it, the plasma membrane. An important conclusion from this article is that the eukaryotic cell did not evolve from bacteria-like prokaryotes, but from a eukaryotic-like cell. You can read more here. 

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de Roos ADG (2005) Origins of introns based on the definition of exon modules and their conserved interfaces. Bioinformatics. 2005, 21:2-9. (pdf)

This was my first article about molecular evolution. I started to be interested in introns after I got hold of a relational intron-exon database and started querying. Trying to find a possible function, I first started off by just looking at the general characteristics of introns (length distributions) but quickly saw that it would be very difficult to discern any biological signal. I started reasoning about their possible role and how proteins would have been assembled in ancient times. I dismissed an introns-late based on mechanistic reasons (by introducing introns, the function of the protein would be impaired) and reasoned that they had to be assembled form smaller parts (exons?). Looking at the mechanistics, the only logical origin of introns would be when they arose when exons were concatenated and thus that they had no initial function apart from the fact that they had to be cut out. As a software architect, I know it is impossible to develop multiple functionalities in one go: interdependencies would prevent independent evolution. I then reasoned that in order for exons to have a functional role as independent units, this should be reflected in their physical appearance: DNA sequence. The article shows that the drived modular structure is reflected at the DNA level and that it brings the possibility for an active shuffling of protein modules. I later refined the theory and shows evidence that exons could have been the building blocks of the functional modules. More can be found here.