François Jacob (1920-2013)

François Jacob. Source.
François Jacob. Source.

François Jacob (1920-2013) is pretty much a household name for biologists. He was a French molecular biologist who was one of the three 1965 Nobel Prize in Physiology or Medicine winners (the other two were André Lwoff and Jacques Monod). Monod and Jacob got it for their work on the lac operon, which laid down the foundations for the study of the mechanisms behind gene regulation and expression. He died 3 days ago. Carl Zimmer already has an excellent article on him, but it doesn’t hurt to help spread his legacy around. I’m sure many of the obituaries will concentrate on the molecular biology he is most famous for, so I want to take a different tack and discuss his contribution to evolution through his highly-influential 1977 Science paper, Evolution and tinkering.

In it, he introduced the world to the concept of gene co-option. Co-option of morphological traits had been well-known, but it was Jacob who showed that “evolutionary tinkering” can occur also at the genetic level, with old genes being repurposed to serve new functions.

Jacob’s envisioning of how this would work stems from his previous work on gene expression and regulation. Instead of requiring completely new genes to produce novel morphologies, genes can simply be controlled by regulator genes. These can have slight changes in activity, which results in the target genes being switched on and off at different times during development, leading to new morphologies at the end. If the new morphologies are successful, then the new pattern of regulatory gene activity is automatically selected for, and the new morphology is retained.

In other words, an important source of morphological novelty can come from evolution “tinkering” with pre-existing systems. It’s similar to cooking: if you’re frying a piece of chicken, adding onions at the start of the frying, in the middle, or at the end of the frying will produce very different flavours (burned vs. caramelised vs. raw). Similarly, if your regulatory gene does its thing at the 4-cell stage, at the start of gastrulation, or the start of neurulation, the end result will be pretty different in each case. Of course, things are more complex in real life, since location and co-interactions also come into play, but I’m simplifying to illustrate the point.

The existence of such mechanisms is now routine knowledge, and examples are present in any evolution and developmental biology textbook, as it’s an important concept for evo-devo.

He did go a bit too far in arguing his case when he claimed that “the probability that a functional protein would appear de novo by random association of amino acids is practically zero”, which is factually wrong (linked is just one random example). In all fairness though, at time of his writing, it was probably a sensible claim to make since there were no examples, so we can’t fault him for it.

That paper was also a rather philosophical one on the nature of evolution, and is an excellent text to use against Intelligent Design creationists with its description of how natural selection is constrained by historical contingency, forcing it to work by tinkering rather than by following a preconceived plan as a designer would. It also contains some excellent quotes and passages on the nature of science itself. Here’s one of my favourites:

[Science] operates by detailed experimentation with nature and thus appears less ambitious, at least at first glance. It does not aim at reaching at once a complete and definitive explanation of the whole universe, its beginning, and its present form. Instead, it looks for partial and provisional answers about those phenomena that can be isolated and well defined. Actually, the beginning of modern science can be dated from the time when such general questions as “How was the universe created? What is matter made of? What is the essence of life?” were replaced by such limited questions as “How does a stone fall? How does water flow in a tube? How does blood circulate in vessels?” This substitution had an amazing result. While asking general questions led to limited answers, asking limited questions turned out to provide more and more general answers.

If you want to read more about him, what better way than to read what he wrote himself? He has a very interesting autobiography from 1988, highly-recommended: The Statue Within: An Autobiography.


Jacob F. 1977. Evolution and tinkering. Science 196, 1161-1166.

Jacob F. 1988. The Statue Within: An Autobiography.

Li C-H, Zhang Y, Wang Z, Zhang Y, Cao C, Zhang P-W, Lu S-J, Li X-M, Yu Q, Zheng X, Du Q, Uhl GR, Liu Q-R & Wei L. 2010. A Human-Specific De Novo Protein-Coding Gene Associated with Human Brain Functions. PLoS Computational Biology 6, e1000734.

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