The genome is a huge haystack. How do you find the needle?

The complexity of the machinery by which our cells run is so extreme that one of the key questions in biological research is, why doesn’t the whole thing just collapse like a house of cards in a tornado? Another way of phrasing this question is to ask, where does the information come from to keep everything running smoothly?

Consider this: the crucial task of gene regulation is carried out in large part by transcription factors, regulatory proteins that recognize and bind to very short, degenerate DNA sequences located somewhere in the rough (sometimes very rough) vicinity of genes. Once they bind, transcription factors recruit the machinery that activates their target genes. (You can also have transcription factors that repress target genes.) This is all good, until you consider the fact that a human transcription factor has to find its target sequences from among the 3 billion base pairs in the human genome. Some plant and fish transcription factors have to search through genomes with more than 100 billions base pairs. So the question is, why don’t transcription factors get lost? Where are they asking for directions?

On finding needles in the genomic haystack Continue reading “The genome is a huge haystack. How do you find the needle?”

Sometimes it is a good idea to browse through my TOC emails

… because I find stuff like this:

Hunter–gatherers and other primates as prey, predators, and competitors of snakes:

Relationships between primates and snakes are of widespread interest from anthropological, psychological, and evolutionary perspectives, but surprisingly, little is known about the dangers that serpents have posed to people with prehistoric lifestyles and nonhuman primates. Here, we report ethnographic observations of 120 Philippine Agta Negritos when they were still preliterate hunter–gatherers, among whom 26% of adult males had survived predation attempts by reticulated pythons. Six fatal attacks occurred between 1934 and 1973. Agta ate pythons as well as deer, wild pigs, and monkeys, which are also eaten by pythons, and therefore, the two species were reciprocally prey, predators, and potential competitors. Natural history data document snake predation on tree shrews and 26 species of nonhuman primates as well as many species of primates approaching, mobbing, killing, and sometimes eating snakes. These findings, interpreted within the context of snake and primate phylogenies, corroborate the hypothesis that complex ecological interactions have long characterized our shared evolutionary history.

Hating snakes is deeply ingrained in our evolutionary past. I feel validated.

Confusing data with theory

Maybe because experiments can be so much work, molecular biologists are just happy to have the data:

Krakauer, et al. “The challenges and scope of theoretical biology”, Journal of Theoretical Biology Volume 276, Issue 1, 7 May 2011, Pages 269–276:

The current absence of a strong theoretical foundation in biology means that there is weak guidance regarding what quantities or variables need to be understood to best inform a general understanding (an explanatory basis) for biological features of interest. An unfortunate result of the absence of theory is that some researchers confuse just having data with ‘understanding’. For example there is a base for collecting and analyzing the most microscopic data: experimental procedures and measurements in a high-throughput transcriptomics study are built around the assumption that transcripts are the primary data to be explained, and in neuroscience, recording from numerous individual neurons. This bias reflects a rather naive belief that the most fundamental data provide a form of explanation for a system, as if enumerating the fundamental particles were equivalent to the standard model in physics.

And here is this kind of thinking in action:

Nurse and Hayles. The cell in an era of systems biology. Cell (2011) vol. 144 (6) pp. 850-854: Continue reading “Confusing data with theory”

Progress in biology?

“I came to work at the MRC Unit for the Study of Structure of Biological Systems in September of 1951…The then tiny unit, composed of Max Perutz, John Kendrew, Francis Crick, and Hugh Huxley, with Sir Lawrence Bragg, the Cavendish Professor, as its very involved patron, had as its objective the understanding of life at its deepest level, the molecular. By so doing, they hoped to transofrm biology from a morass of seemingly limitless and often boring facts into an intelectually satisfying discipline like physics and chemistry.”

– James Watson, “Minds That Live For Science”, in A Passion for DNA.

60 years later:

“Biology is entering a period where the science can be underlaid by explanatory and predictive principles, rather than little bits of causality swimming in a sea of phenomenology.”

– Eric Davidson, quoted in Erica Check Hayden,”Life is Complicated,” Nature April 1, 2010

Will we ever escape from the morass of limitless, boring facts?

On reading The Double Helix

I recently reread The Double Helix because I am interested in understanding why people began thinking that the structure of DNA was an important problem. Watson and Crick are the most famous 20th century biologists – if you ask a random person on the street to name a 20th century biologist, the most likely response is a blank stare, but the second most likely response is Watson and Crick. Why? Why did the structure of DNA turn out to be so enlightening, and why did people think it was an important problem in the early 50’s?

I first read this book in the 90’s before I became a scientist, and so I missed much of Watson’s insight into how scientists sniff out and pursue a good problem. Watson argues that only a few key people were thinking of DNA as being the key to heredity, but things clearly weren’t going to stay that way for long – DNA’s significance would soon be recognized, and so those hoping to solve the problem had to work fast before more competitors arrived.

The key to understanding The Double Helix is to figure out when Watson is accurately describing the quirky way in which scientific personalities interact in the process of pursuing hot science, and when Watson is being an asshole. Continue reading “On reading The Double Helix”