Tuesday, October 31, 2017

The history of DNA sequencing

This year marks the 40th anniversary of DNA sequencing technology (Gilbert and Maxam, 1977; Sanger et al., 1977)1 The Sanger technique soon took over and by the 1990s it was the only technique used to sequence DNA. The development of reliable sequencing machines meant the end of those large polyacrylamide gels that we all hated.

Pyrosequencing was developed in the mid 1990's and by the year 2000 massive parallel sequencing using this technique was becoming quite common. This "NextGen" sequencing technique was behind the massive explosion in sequences in the early part of the 21st century.2

Even newer techniques are available today and there's a debate about whether they should be called Third Generation Sequencing (Heather and Chain, 2015).

Nature has published a nice review of the history of DNA sequencing (Shendure et al., 2017). I recommend it to anyone who's interested in the subject. The figure above is taken from that article.


1. Many labs were using the technology in 1976 before the papers were published.

2. New software and enhanced computer power played an important, and underappreciated, role.

Heather, J.M., and Chain, B. (2015) The sequence of sequencers: The history of sequencing DNA. Genomics, 107:1-8. [doi: 10.1016/j.ygeno.2015.11.003]

Maxam, A.M., and Gilbert, W. (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Methods in enzymology, 65:499-560. [doi: 10.1016/S0076-6879(80)65059-9]

Sanger, F., Nicklen, S., and Coulson, A.R. (1977) DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, 74:5463-5467. [PDF]

Shendure, J., Balasubramanian, S., Church, G.M., Gilbert, W., Rogers, J., Schloss, J.A., and Waterston, R.H. (2017) DNA sequencing at 40: past, present and future. Nature, 550:345-353. [doi: 10.1038/nature24286]


11 comments :

  1. I think 2000 is a bit too early for pyrosequencing in practice (rather than theory). I worked at a sequencing center around then and we used all ABI Sanger machines until 454 released its first sequencer in 2005. I agree with you that had not computing improved along with the sequencing methods that we wouldn't have been able to deal with the much greater amount of data that 454, and then Illumina, machines produced.

    ReplyDelete
  2. The one thing no method should be called is "next generation" sequencing. Yet it did get called that. Genomicists and molecular geneticists blithely accepted a marketing term without thinking about how well it would wear. They now have to say "back in the days of next generation sequencing ..." Embarrassment is called for.

    ReplyDelete
    Replies
    1. See also the "Modernist" movement in the late 19th and early 20th century. Obviously any movement is going to be stop being modern after a while. That's why the postmodernists called themselves that. But now we're mostly past them as well, so postpostmodernist?

      Delete
    2. The next generation of children will become grandparents someday. I don't have a problem with using the term for new sequencing technologies. It's not as if they are calling them the last generation of sequencing technology.

      Delete
    3. Not to mention the Modern Synthesis. I suppose that it is "modern" in the same sense that all the post-world-war-I intellectual movements, from art to architecture to music, were "modern".

      Delete
    4. ... and not to mention "supercomputer", an exciting 1980s machine.

      Delete
  3. I'm old enough that I remember radiolabeled dNTPs and all the annoying tedium that goes along. It wasn't until my last year of graduate school that we got an ABI machine. Now that was a relief.

    ReplyDelete
    Replies
    1. I didn't find it tedious. The elegance behind how it works kept me fascinated. The particular method we used called for just half a micro-litre of radioactive "mark" solution. Half a micro-litre! The mix was then divided into four reactions each with its specific ddNTP, and only around 40% of each reaction went into the well (!!). That was enough to get the autoradiography (an all nighter). As I said, fascinated.

      Delete
    2. Elegant and tedious are not mutually exclusive. Now me, I find all the elegance to inhere in the Sanger process itself, not how it was performed, and was perfectly content to leave the labeling to fluorescent dyes, reaction termination to chance during cycle sequencing, and reading to a nice little laser. And I got more sequencing done during the last year of my thesis work than the preceding several years combined.

      Delete
  4. I was lucky enough to be able to perform 1 radioactive sequencing experiment, before the ABI took over in our lab. I do know many of my colleagues in my lab sighed a huge sigh of relief when the ABI took over. As some of them ran many sequencing gels each week.

    ReplyDelete
  5. One of the amazing things about Sanger is that, even though he was already a Nobel laureate at the time, he actually contributed experimentally to the 1977 PNAS paper as much as his technician (Alan Coulson, the last author of the paper).

    I highly recommend reading Sanger's super short autobiography: http://www.annualreviews.org/doi/pdf/10.1146/annurev.bi.57.070188.000245

    ReplyDelete