New advances in DNA sequencing technology have been receiving a lot of press, but mostly in the context of how DNA sequencing is going to make personalized medicine possible. Your physician will some day be able to prescribe drugs and give you advice on disease prevention, all based on a reading of your DNA. Obviously that day is not here quite yet; however, the amazing power of next-generation DNA sequencing is already transforming what goes on in a biology lab.

To see this, we can take a look at an old technology and look at the changes it has gone through, from its pre-genome-era state in the 80's and 90's, to its transformation into a genome-scale tool around the turn of the millennium, to its latest incarnation during this emerging era of massive, cheap DNA sequencing. This technology, called chromatin immunoprecipitation (or ChIP), has been a critical tool in studies of how genes are regulated. ChIP, in its current, next-generation DNA sequencing form, is opening up some stunning new approaches to studying gene regulation.

Part 1 on The Plausibility of Life

Darwin is famous for convincingly arguing that natural selection can explain why living things have features that are well-matched to the environment they live in. In the popular consciousness, evolution is often thought of as natural selection acting on random mutations to produce the amazing tricks and traits found in the living world. But “random mutation” isn’t quite right - when we describe evolution like this, we pass over a key problem that Darwin was unable to solve, a problem which today is one of the most important questions in biology. This key problem is the issue of variation, which is what biologists really mean when they talk about natural selection acting on random mutations. Variation and mutation are not the same thing, but they are connected. How they are connected is the most important issue covered Kirschner and Gerhart’s The Plausbility of Life. It is an issue Darwin recognized, but couldn’t solve in those days before genetics really took off as a science.

Natural selection really works on organisms, not directly on mutations: a particular cheetah survives better than other cheetahs because it can run faster, not because it has a DNA base ‘G’ in a particular muscle gene. A domesticated yeast can survive in wine barrel because of how it metabolizes sugar, not because of the DNA sequence of a metabolism gene. I know what you’re thinking: this is just a semantic game over proximal causes. But this is not just semantics, it is a real scientific problem: what is the causal chain that leads from genotype to phenotype, that is, from an individual organism’s DNA sequence, mutations included, to the actual physical or physiological traits of the complete organism?