What I taught today: molecular genetics and basic concepts
I was bad. I didn’t post my summary last week, so this is actually what I taught a week ago and what I taught today.
Previously, I’d given an overview of the foundations of modern developmental biology in embryology and anatomy. I gave them more history last week, only not so ancient: what led to the modern focus on patterns of gene expression? In the early 20th century, it was all Entwicklungsmechanik, the experimental manipulation of embryos and analysis of morphology in order to infer mechanisms of transformation (that’s a bit of an oversimplification: we were also interested in physiology, and some vital dyes, for instance, also let us see patterns of metabolic activity). But all that was indirect. We were looking at the output of a black box, but we couldn’t see what was actually going on inside the black box, where all the action was. And everyone knew it. Here’s what TH Morgan said in 1927:
“One of the most important questions for embryology relating to the activity of the genes cannot be answered at present. Whether all genes are active all the time, or whether some of them are more active at certain stages of development than others, are questions of profound interest.”
Think about that. In the early days of developmental biology, we didn’t even know whether there was differential gene activity or not; it was considered a reasonable possibility that all the genes were just doing their work, whatever it was, all the time in every cell, and that differences between cells emerged farther downstream, in biochemical interactions. But they knew this was an important question. They knew that we had to look at the activity of individual genes…they just didn’t have the tools yet. So it was back to hacking up embryos and trying to infer causes from aberrations.
The change emerged gradually, but there were a couple of watershed moments where everyone looked up and noticed that hey, we do have ways of looking at genes directly. One was the work of Ed Lewis, a most excellent geneticist who used the tools of genetics to look directly at mutations that caused changes in fly morphology, in the 1960s. This was amazing stuff — the papers he wrote were beautiful and complex and very, very genetical — but it was written in a language that most developmental biologists of the day were unprepared to read. They were genetics papers. But I think they laid a foundation: if you want to do development, you’d better learn about genetics.
The second big event was the saturation mutagenesis screen of Christiane Nusslein-Volhard and Eric Wieschaus, about 20 years later. This work was also built on an understanding of genetics, but also used the tools of molecular biology. It was another lesson: if you want to do development, you’d better learn about molecular biology. I defined this field for the students:
Modern developmental biology is the study of differential patterns of gene expression and their effects on cells, tissues, organs, and organisms.
I also talked about the Evo-Devo ‘Revolution’, but I put a different twist on it. This is usually expressed by developmental biologists as the new change in thinking, the one where we’re going to teach everyone else how important development is to the field of biology as a whole, but I see it as something completely different. Evo-Devo is the discipline in which developmental biologists finally woke up and started paying attention to all the work other biological disciplines have done — we aren’t transforming them, they’re revolutionizing us by giving us the great good gifts of genetics and molecular biology to finally allow us to directly look at genes and gene interactions.
(I didn’t talk about this today, but will later in the course: another discipline, Eco-Devo, is the field where we also start respecting the importance of ecology and population genetics to development. Developmental biologists aren’t the masters, but the students — this field is so great because we’re benefitting from the synergistic incorporation of so many other fields. Just some of us are a little too cocky about it, and have a slightly skewed perspective.)
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