After five grueling but interesting days, the Cold Spring Harbor Labs Biology of Genomes has wrapped up. So where is genomics heading?
A few lessons: Continue reading “CSHL Biology of Genomes Wrap-Up”
After five grueling but interesting days, the Cold Spring Harbor Labs Biology of Genomes has wrapped up. So where is genomics heading?
A few lessons: Continue reading “CSHL Biology of Genomes Wrap-Up”
Eric Smith, “Thermodynamics of Natural Selection” (PDF):
The two paradigms dominating biological theory are the machine-like functioning of componentry (increasingly elaborated in molecular biology) (Alberts, 2002), and the Darwinian framework for understanding the stochastic dynamics of death and reproduction (Gould, 2002; Lewontin, 1974). The representation of biological processes as machines is often by way of models, which represent control flow and causation, and for which the goal is to conceptually or quantitatively reproduce typical observed behaviors (mechanisms of binding, Stormo and Fields, 1998, transcription or translation, Berman et al., 2006, cell cycling, Novak et al., 2001, regulation of cell division, Tyson et al., 2002 or metabolic pathways, Holter et al., 2001, etc.). Energy naturally appears in these contexts as an input, as a quantitative constraint, or as a medium of control. However, models constructed for the purpose of illustrating causality often diminish the importance of the incursion of error at all levels of organization and the consequent energetic costs of systemic error correction, and so are not suited to composition into a system-level description of either emergence or stability. At the other extreme, Darwinian selection is a purely informational theory, concerned with emergence and stabilization through statistical processes. Yet, for lack of a comprehensive theory of individual function, models of the dynamics resulting from selection inevitably take for granted (Hartl and Clark, 1997) the platform of physiology, growth, development, and reproduction, decoupling the problem of information input from energetic constraints on the mechanisms by which it occurs.
One of the keys to success in life is to regulate your genes properly. Genes are regulated by transcription factor proteins, which have to navigate their way around the genome and bind particular DNA targets. The problem is that there are only a few correct targets and the genome is large. So an obvious question is, why don’t transcription factors get lost? Do they stop and ask for directions? Where is the information for genome navigation coming from?
The answer to this question is still being worked out for eukaryotes, but it has been solved for E. coli. Peter von Hippel and Otto Berg largely figured out the answer in their classic 1986 paper “On the specificity of DNA protein interactions.” E. coli’s solution for making gene regulation manageable is simple and elegant, because this bacterium has the virtue of possessing a small genome. Let’s take a look at how genome navigation works in a bacterium: Continue reading “How to find your way in E. coli without stopping for directions”
Ryan Gregory at Genomicron mocks an inane press release about a supposedly new evolutionary theory – the idea that endosymbionts will lose genes when their hosts or other microbes in their community can provide the functions of those genes. This is an old and widely established idea, so why anyone with any knowledge of recent evolutionary biology would play up this idea as novel is beyond me.
Sadly, the ignorance isn’t limited to whatever flack wrote the press release – at least one of the scientists involved is portrayed as the same misunderstanding of evolution that many creationists have:
“A common assumption about evolution is that it is directed toward increasing complexity,” said Erik Zinser, associate professor of microbiology. “But we know from analysis of microbial genomes that some lineages trend toward decreasing complexity, exhibiting a net loss of genes relative to their ancestor.”
Okay kids, repeat after me: evolution is not based on an assumption of increasing complexity. Increasing complexity (leaving aside the fact that the word complexity is terribly vague and non-quantitative) often happens in evolution, but we don’t assume that this is what should happen.
UPDATE: It could be that I’m being unfair to Dr. Zinser, that he’s being selectively quoted in a bad way by the same person who wrote the rest of the misguided press release. If that’s true, then all of my disdain is reserved for the anonymous press release writer.
There is something dissatisfying about our current explanations of how the genome exerts its effects on the cell. This is particularly true of the non-protein-coding regulatory regions of the genome, which, as we all know, make up a substantially larger fraction of the genome than those DNA sequences that encode proteins.
So what is that we don’t understand? Rather than give a wordy and abstract explanation, let’s go with an analogy: our poor understanding of how the genome operates is like my poor understanding of how a CD player works.
Let’s start with what I do know about CD players (with a little help from Wikipedia, which I hate but still refer to dozens of times per day.) The data in a CD is encoded as little pits in a polycarbonate surface. Behind the polycarbonate surface is the shiny layer of the CD, and so the pattern of pits can be scanned by using a photodiode to detect laser light that is reflected off the CD. The pits change how the light is reflected, which changes the electrical signal that is emitted by the photodiode. Those output electrical signals are amplified, passed to a loudspeaker and finally to my ears and slightly buzzed brain. (Obviously I’m talking about listening to music after work.) Continue reading “I don’t understand my CD player or my genome”