Despite our discussions about genome assembly and annotation in class as well as our own command line work in this area, the 1995 article by Fleischmann et al was difficult to read and fully comprehend. While many of the details remain misunderstood for me, it was interesting to see all the ways that the researchers developed methods to assemble the genome. I think my biggest takeaway was how creative the research team was given the limitations of technology available to them and the novelty of molecular genomics at that point in time. Whether it be the manipulation of traditional culturing techniques, like the use of E. Coli host cells deficient in recombination and restriction functions to prevent rearrangements and deletions, or antibiotic plates to inhibit the selection of the most rapidly growing cells, it was really inspiring to read about scientists who were able to use simple tools in an effect manner (1). Efforts to increase randomization throughout the process were more prevalent than I expected, and I was also surprised to see how they interpreted redundancy in different aspects of the process, and used it to differentiate the appropriate order of sequences.
I was grateful that I read the Nowak article in conjunction with the primary research paper, because it really highlights the importance of this accomplishment and conveys to a more general audience the overwhelming potential of genomics. – especially microbial genomics. While it did not shed light on the details of the methodology behind genome assembly, it was an effective companion to the latter part of the original article. It highlighted certain genomic findings, whether it be chromosomal organization, the lack of certain genes or the presence of unknown genes, that helped bring more context to those described in the Fleischmann et al article. The missing genes encoding enzymes for the tricarboxylic acid cycle struck me as being very interesting, since in my education, most of classes have blanketed the TCA cycle as uniform and highly conserved across all taxonomic domains (1, 2). Being able to see the perspective on genome science in its youth and the important role that researchers played in developing the technology and processes, it made me appreciate the technology that we have available to us now. My own experience in molecular microbiology is limited both in time and scope, so advanced technology, whether it be for PCR amplification, quantification methods or sequencing itself, has always been available to me. I feel like they had to do a lot of detailed processing while I relied on advanced programs and algorithms developed by more advanced scientists and programmers to do those tasks for me. It makes me wonder about how we, as humans, advance our knowledge and understanding. Is it better to develop under the pressures or limitations of your environment and what is available to you, like those in the article, or to study the theories but rely on technology to perform the work due to the constrictions of time and resources?Comparing what they did at that point to what I know about sequencing technology from this course and what I have done in a lab, I feel very grateful for the luxury of sequencing programs however I am in awe of what they were able to generate and the accuracy of their data.
- Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A, Bult C, Tomb J, Dougherty B, Merrick J, al. e. 1995. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496-512.
2. Nowak R. 1995. Bacterial genome sequence bagged. Science 269:468-470.
