On the origin of species… …and what it has to do with me.

archeopteryxI surely do believe in evolution. It’s a scientific fact. And I take pride in teaching my children the reptile- and bird-like features of Archaeopteryx when we go to the museum, something that just blew me away with fascination when I was a student at university and was taught convincing proof of the evolutionary process. However, with some youthful arrogance and academic ignorance, already back then I believed I would know just enough knowing that some sequence feature was “conserved” or that there was a “homologous sequence”.

Two of my first real papers had some sort of evolutionary touch on them: Tracheal development and the von Hippel-Lindau tumor suppressor homolog in Drosophila and Drosophila awd, the homolog of human nm23…. Adding “homolog” to your title makes the story sell better, and I thought I had understood evolution. And, of course, being primarily interested in a particular protein, the identification of an ortholog was as much as looking at DNA sequence would reveal about its evolution (thank god I kept my mouth shut about that, I realise now!). Even just six years ago at a very focussed regulatory genome informatics meeting I discovered with some amusement and slight embarrassment that I was the only participant of a group of about twenty who had never heard about Kimura before, and I wondered how this lack of knowledge could go undetected for so long.

With the arrival of entire genome sequences and the revolution following next-generation sequencing technologies, suddenly all things DNA sequence have become relative. There is no more “the human genome” or “the fly genome”. We’re finally able to look at sequences within populations, and amongst closely and not so closely related species. As a result of being able to ask really exciting evolutionary or population genetics questions, just saying something “is conserved on the sequence level” now officially isn’t addressing a question anymore, nor can you pretend to do evolutionary biology. I can live with that!

So how much should I know? In the context of a recent row over the validity of statements (see OpenHelix blog for a brief summary) in the ENCODE publications, Rosie Redfield (@RosieRedfield) said on Twitter “The tragedy is that a lot of smart hard-working biologists think understanding evolution is optional“, and I felt that awkward tension of embarrassment again (“guilty as charged!”), and she continued “Think just-so stories and hand-waving are sufficient“. Well, okay, here it comes: In two of my genomicsy stories concerning insulator binding, I made statements about the evolutionary conservation of these sites in a “just-so manner”, too, without any deeper followup. (I still believe Su(Hw) and CTCF sites are conserved, but how much is a summary score such as the phastCon across a bunch of insect species really tell you?).

I’m not a complete novice and indeed I’m teaching comparative genomics as a subject to both computational biology as well as genetics students. But this is all fairly technical and, I think, entirely independent from really understanding evolution on the sequence and genome level. Although I can run the software, explain the algorithm and implementation, and probably even interpret the immediate output, I cannot put the findings into the context of current evolutionary research. My mindset is still very much “It’s conserved” or “It’s not conserved”. It’s as simple as that, because me and sequence evolution haven’t had a great start, and teaching an old dog new tricks… ….takes some time. Should I just shut up about any evolutionary implications for now?

Comments welcome!

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