32.2: Reading and Writing Genomes

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As a motivation, consider the following question: Is there any technology that is not biologically motivated or inspired? Biology and our observations of it influence our lives pervasively. For example, within the energy sector, biomass and bioenergy has always existed and is increasingly becoming the focus of attention. Even in telecommunications, the potential of quantum-level molecular computing is promising, and is expected to be a major player in the future.

Church has been involved in molecular computing in his own research, and claims that once harnessed, it has great advantages over their current silicon counterparts. For example, molecular computing can provide at least 10% greater efficiency per Joule in computation. More profound perhaps is its potential effect on data storage. Current data storage media (magnetic disk, solid-state drives, etc.) is much less (billions times) dense than DNA. The limitation of DNA as data storage is that it has a high error rate. Church is currently involved in a project exploring reliable storage through the use of error correction and other techniques.

In a 2009 Nature Biotechnology review article [1], Church explores the potential for efficient methods to read and write to DNA. He observes that in the past decade there has been a 10$\times$ exponential curve in both sequencing and oligo synthesis, with double-stranded synthesis lagging behind but steadily increasing. Compared to the 1.5$\times$ exponential curve for VLSI (Moore’s Law), the increase on the biological side is more dramatic, and there is no theoretical argument yet for why the trend should taper off. In summary, there is great potential for genome synthesis and engineering.

Did You Know?

George Church was an early pioneer of genome sequencing. In 1978, Church was able to sequence plasmids at $10 per base. By 1984, together with Walter Gilbert, he developed the first direct genomic sequencing method [3]. With this breakthrough, he helped initiate the Human Genome Project in 1984. This proposal aimed to sequence an entire human haploid genome at $1 per base, requiring a total budget of $3 billion. This quickly played out into the well-known race between Celera and UCSC-Broad-Sanger. Although the latter barely won in the end, their sequence had many errors and gaps, whereas Celera’s version was much higher quality. Celera initially planned on releasing the genome in 50 kb fragments, which researchers could perform alignments on, much like BLAST. Church once approached Celera’s founder, Craig Venter, and received a promise to obtain the entire genome on DVD after release. However, questioning the promise, Church decided instead to download the genome directly from Celera by taking advantage of the short fragment releases. Using automated crawl and download scripts, Church managed to download the entire genome in 50 kb fragments within three days!