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Three phases of genome sequencing and their consequences for science and medicine

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Over the last 20 years genome sequencing has had a profound impact on the biological sciences and related applications in medicine and agriculture. There have been three phases, each associated with a change in technology. The first, in which Fred Sanger’s sequencing chemistry was automated in the first sequencing machines, led to the reference genome sequences of human and a few other key species. This enabled genomic biology. In the second phase, highly parallel “next generation” short read sequencing technologies allowed sequencing thousands of humans and individuals from other species for which a reference was already available, giving us the ability to study genetic variation directly. This has led to rapidly increasing applications of DNA sequencing in clinical medicine, and has connected two scientific areas, population genetics and molecular biology. In the last few years, new single molecule sequencing technologies have become viable at scale, giving sequencing reads hundreds of times longer than the previous methods, which allow us to efficiently determine from scratch the genome sequences of arbitrary species. Extrapolating long term trends of cost reduction and throughput increases, we can see we are entering a third phase of genome sequencing in which we will sequence all million or so known species, with potential major consequences for the study of diversity and evolution, and for conservation.

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