DNA Replication in E. coli: The Problem

I've started reading microcosm by my favorite science writer, Carl Zimmer [Buy This Book!]. Watch for a review, coming soon.

I was mildly disappointed to see Carl repeat a common myth about DNA replication in E. coli on page 29. Since we often use this myth to teach critical thinking in our undergraduate classes, I thought it would be worthwhile to discuss it here.

Today I'm going to present the problem and let everyone think about a possible solution. On Sunday, I'll publish the answer. (If you know the solution, you are not allowed to post it in the comments—I'll delete those comments. You can ask for clarification or speculate.)

Here's what Carl says at the top of page 29.

E. coli faces a far bigger challenge to its order when it reproduces. To reproduce, it must create a copy of its DNA, pull those chromosomes to either end of its interior, and slice itself in half. Yet E. coli can do all of that with almost perfect accuracy in as little as twenty minutes.

Today, we're not concerned about the 20 minute generation time but I note, for the record, that the average generation time of E. coli, in vivo, is about one day. I also want to mention that the 20 minute generation time is an extreme example that's achieved only under the most extraordinary circumstances. Typical generation times in the lab are about 30 minutes.

However, that's not the problem. Let's assume a generation time of 20 minutes.

In the next paragraph Carl says ...

The first step in building a new E. coli—copying more than a million base pairs of DNA—begins when two dozen different kinds of enzymes swoop down on a single spot along E. coli's chromosome. Some of them pull the two strands of DNA apart while others grip the strands to prevent them from twisting away or collapsing back on each other. Two squadrons of enzymes begin marching down each strand, grabbing loose molecules to build it a partner. The squadrons can add a thousand new bases to a strand every second.

What Carl is referring to the the assembly of replication complexes (replisomes) at the origin of replication. Once those complexes are assembled, replication fires off and proceeds in opposite directions (bidirectionally) until the two fork meet at the opposite side of the chromosome.



Carl is correct when he says that the forks move at 1000 nucleotides per second. Later on in his book he mentions that the size of the E. coli chromosome is 4,600,000 base pairs or 4,600 kb (p. 116). At 1000 nucs per second it would take 4600 second to replicate this DNA if there was only one replication fork. Since there are two, it will take 2,300 seconds.

You can do the math. This is 38 minutes. It is a correct number—it takes at least 38 minutes to replicate the E. coli chromosome, not 20 minutes as stated earlier. It is true that the generation time of E. coli can be as short as 20 minutes under extraordinary circumstances.

Here's the problem. How can E. coli divide faster than it can replicate it's chromosome?

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