What is this website?
This is an Open Educational Resource created through the North Carolina State University Biotechnology Program. Our goal is to provide you with the basic information about an important topic in biology and biotechnology. Even more importantly though, we hope to provide you with cues to draw your own conclusions and become part of the scientific research community. As you read you will either see in-line citations of primary research, or be able to find the primary literature used to compose background information on our Learn More! page. On that page you will also find links to labs and funding agencies, and throughout the website you will see opportunities to submit your opinion back to the creators, who will compile and post the results regularly.
What is the origin of replication and why should I care?
What makes the origin of replication interesting is its role in our complex, extraordinary genetic replication system itself. All life on earth is bound together by the use of nucleic acid—DNA or RNA—to carry information. But believe it or not, the fact that DNA is the molecule of genetic information was not a settled matter until 1944. That was the year that Oswald Avery, Colin MacLeod and Maclyn McCarty published research proving that DNA, and no other type of biological molecule, was able to confer traits from one bacterium to another. The physical structure of DNA was not resolved until 1953 when Watson and Crick published the double helix model. So, although we now start learning about DNA in elementary school, we have only been studying the details of how replication actually works for a few short decades! In that time, many debates about DNA have arisen, and understanding the origin of replication involves an answer to one of the oldest ones: the ‘replication problem.’
The replication problem arose immediately after the double-helix structure was widely accepted. In order to copy and express genes, the two strands of a DNA molecule must be separated, but when even a simple organism like yeast has a genome of about 12,000,000 base pairs, how could we possibly expect to unwind the DNA and wind it back up in precisely the same order without getting tangled? Max Delbruck, a prominent molecular biologist who corresponded closely with James Watson, considered this process so unlikely that he proposed that DNA was chopped into small pieces, replicated, and then reassembled end-to-end rather than chromosomes being ‘untwiddled’ for replication.
Delbruck's question was answered in the 1950s when the experiments of Meselson and Stahl proved that each whole strand does indeed replicate without breaking apart. This also meant that the replication machinery must somehow ensure that the entire DNA molecule is copied in a single process, without missing segments and with minimal errors. In experiments from the 1960s to the 1980s, it was discovered that part of how this is ensured is that in all types of organisms, replication of DNA always begins at the same place (or places). Thisspecial part of the chromosome with specific sequence and structural features is called the origin of replication.
Although there is variation across organisms, the nature of the origin of replication is similar at the molecular level. The origin contains a large number of adenine and thymine bases (A and T), compared to the two other bases, G and C, adenine and thymine are more weakly bound and make it easier to separate the strand of DNA. The origin of replication may be as short as 13 base pairs or as long as several hundred, but if the sequence is longer it simply contains repetitions of a similar short sequence. And although specific proteins vary, replication at the origin always begins by recruiting specialized proteins that recognize, bind to, and unzip the sequence found at the origin of replication.
Falaschi and Giacca proposed six general characteristics that define an origin of replication: