This process allowed Sanger et al. to sequence the first genome, of a \(\varphi X174\) bacteriophage, in 19772. Although revolutionary, this method was costly, time consuming and labor intensive. Adjustments to this method were made in order to make it faster and less expensive. An important step was to change the way ddNTPs were marked. By using fluorescent markers, each base having a distinct “color”, we can eliminate the need to have 4 different environments and lanes in the gel35,36. This also paved the way for automating sequencing, each fluorescently marked band can be excited with a laser, and the resulting specific wavelength can be recorded by optical systems and the corresponding base automatically deduced37 (Also see Figure 1.3). Other improvements were made such as using capillary electrophoresis instead of gel electrophoresis.
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