TWiV 162: Transcription

transcriptionHosts: Vincent Racaniello, Rich Condit, and Alan Dove

Vincent, Rich, and Alan continue Virology 101 with a discussion of transcription, the process of making mRNA from a DNA template.

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Rich – 3D vaccinia virion
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SarahCritical Thinking (pdf),  diagnosing respiratory infections by gene signature (Cell Host Micro), and One Health Initiative (CDC page)

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Har Gobind Khorana, master decoder

genetic codeMost students of elementary biology will have seen the table at left that depicts the genetic code. HG Khorana was one of several scientists who determined, in the 1960s, the amino acids specified by each three-letter combination of bases. As long as I have been at Columbia University I have had a copy of this table on my office wall.

Khorana reminisces how the finding that genes are nucleic acids set the stage for his work on decoding:

While it is always difficult, perhaps impossible, to determine or clearly define the starting point in any area of science, the idea that genes make proteins was an important step and this concept was brought into sharp focus by the specific one gene-one enzyme hypothesis of Beadle and Tatum. The field of biochemical genetics was thus born. The next step was taken when it was established that genes are nucleic acids. The transformation experiments of Avery and coworkers followed by the bacteriophage experiments of Hershey and Chase established this for DNA and the work with TMV-RNA a few years later established the same for RNA. By the early 1950’s it was, therefore, clear that genes are nucleic acids and that nucleic acids direct protein synthesis, the direct involvement of RNA in this process being suggested by the early work of Caspersson and of Brachet.

The first triplet to be decoded was UUU, which specifies the amino acid phenylalanine. This work was done by Nirenberg who found that an RNA consisting of repeating U residues could be translated into a protein containing only phenylalanine. Codons for lysine (AAA) and proline (CCC) were similarly discovered using RNAs containing only A or C. Khorana used both enzymatic and chemical synthesis of oligonucleotides to decipher much of the remaining code. A good account of his work can be found in his Nobel lecture (pdf).

Khorana, together with Robert Holley (structure of tRNA) and Marshall Nirenberg, received the Nobel Prize in Physiology or Medicine in 1968 for their work on deciphering the genetic code.

Viral bioinformatics: Introduction to multiple sequence alignment

This week’s addition to the virology toolbox was written by Chris Upton

Generating multiple sequence alignments (MSA) is one of the most commonly used bioinformatics techniques. The “sequences” to be compared can be DNA (promoters, genes, genomes) or proteins. Note that the length and number of sequences to be aligned has an impact on the methods (algorithms) that can be used; what is suitable for aligning 20 proteins probably won’t work for alignment of 5 poxvirus genomes (200 kb each).

Some useful links:

So you see, there lots of options (did you say: “too many!”?). Further confusion may arise because 1) the same algorithm may be used in many different software programs, and 2) referencing a software package may give no clue to the algorithm used. For many molecular biologists, Clustal is synonymous with sequence alignment. However, newer algorithms such as T-Coffee and MUSCLE are often offered in current software packages, and may be faster and more accurate.

Specialized alignment tools are almost always needed for long, genome sized DNA sequences.

In this set of posts, I’ll provide some information on favorite general MSA tools (that are free) that should be useful to the average molecular virologist. The lists noted above provide a multitude of tools, but many are for specific analyses.

Virology lecture #6: RNA-directed RNA synthesis

Download: .wmv (324 MB) | .mp4 (76 MB)

Visit the virology W3310 home page for a complete list of course resources.

Virology lecture #3: Genomes and genetics

Download: .wmv (333 MB) | .mp4 (75 MB)

Visit the virology W3310 home page for a complete list of course resources.

TWiV 60: Making viral RNA

TWiV_AA_200Hosts: Vincent Racaniello and Dickson Despommier

Vincent and Dick continue Virology 101 with a discussion of how RNA viruses produce mRNA and replicate their genomes.

Click the arrow above to play, or right-click to download TWiV #60 (51 MB .mp3, 71 minutes)

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Below is a video of TWiV 60, which highlights the diagrams I referred to during the podcast.

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How viruses are classified

virosphere-2005For the first 60 years of virus discovery, there was no system for classifying viruses. Consequently viruses were named haphazardly, a practice that continues today.

Vertebrate viruses may be named according to the associated diseases (poliovirus, rabies), the type of disease caused (murine leukemia virus), or the sites in the body affected or from which the virus was first isolated (rhinovirus, adenovirus). Some viruses are named for where they were first isolated (Sendai virus, Coxsackievirus), for the scientists who discovered them (Epstein-Barr virus), or for the way people imagined they were contracted (dengue = ‘evil spirit’; influenza = ‘influence’ of bad air).

By the early 1960s, new viruses were being discovered and studied by electron microscopy. As particles of different sizes, shapes, and composition were identified, it became clear that a systematic nomenclature was needed. Lwoff, Horne, and Tournier suggested a comprehensive scheme for classifying all viruses in 1962. Their proposal used the classical Linnaean hierarchical system of phylum, class, order, family, genus and species. The complete scheme was not adopted, but animal viruses were soon classified by family, genus, and species.

An important part of the scheme proposed by Lwoff and colleagues is that viruses are grouped according to their properties, not the cells they infect. The nucleic acid genome was also recognized as a primary criterion for classification. Four characteristics were to be used for the classification of all viruses:

  1. Nature of the nucleic acid in the virion
  2. Symmetry of the protein shell
  3. Presence or absence of a lipid membrane
  4. Dimensions of the virion and capsid

Other characteristics which were subsequently added include the type of disease caused, and which animals and tissues are infected. With the development of nucleic acid sequencing technologies in the 1970s, genomics has played an increasingly important role in taxonomy. Today new viruses are assigned to families based on the nucleic acid sequence of their genome.

The International Committee on the Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. A complete catalog of known viruses is maintained by the ICTV at ICTVdb. Although the ICTV nomenclature is used to classify animals viruses, plant virologists do not place their viruses into families and genera, but use group names derived from the prototype virus.

Because the viral genome carries the blueprint for producing new viruses, virologists consider it the most important characteristic for classification. Next we’ll discuss the Baltimore classification, an alternative scheme based on the viral genome.

Lwoff, A., Horne, R., & Tournier, P. (1962). A system of viruses. Cold Spring Harb Symp Quant Biol., 27, 51-55

Buchen-Osmond, C. (2003). The universal virus database ICTVdB Computing in Science & Engineering, 5 (3), 16-25 DOI: 10.1109/MCISE.2003.1196303