Can genomics/meta-genomics replace transimission electron microscopy (TEM)?

Can genomics replace electron microscopy?

next-generation sequencing

This might be suggested by the rise of rapid sequencing and the ensuing increased availability of completely sequenced virus genomes. It is indeed advocated in discussions by unconditional partisans of genomics. The answer is round ‘‘no.’’ Genomics gives us the genome and genes, thus the elementary building blocks of a virus. It also gives gene order and direction of transcription, and it identifies genes coding for proteins with homology to known enzymes or virion components, restriction-modification enzymes, capsid protein size, or the length of tape measure proteins. Further, genomics indicates horizontal gene transfer or gene swapping, may indicate relationships between virus groups and individual viruses and allows for quantification of relationships and the construction of phylogenetic trees. All this provides unprecedented insights into virus evolution and is a precious help in phage classification.

However, electron microscopy provides information on virion structure, while genomics does not show the whole virus, gives not a single dimension, provides no information on virus structure and physicochemical properties, does not identify unusual bases such as 5-hydroxymethylcytosine, and predicts only some biological properties, such as a lysogenic nature. No sequence can indicate simple things such as the size of phage capsids, their geometry, or the number of capsomers. If, as likely, the length of phage tails depends on the length of ruler protein genes (Katsura and Hendrix, 1984; Pedulla et al., 2003), this must be ascertained by the measurement of many phage tails under strict magnification control. Unfortunately, this has not been the case. If, as pretended, a genome contains all information on a virus, we have not yet found the instruction manual to read it. 

With respect to virus identification, genomics generally does not indicate to which virus family a tailed phage belongs; for example, there are no sequences specific to Myo-, Sipho-, or Podoviridae. Only in the case of small polyhedral or filamentous phages (Micro-, Levi, and Inoviridae) does genomics allow for the identification of virus families (Ackermann and Kropinski, 2007). Similarly, a Bacillus tectivirus from the earthworm gut was identified by genomics alone without the benefit of electron microscopy (Schuch et al., 2010). However, in a general way, investigation of a complete virus sequence may take months and is infinitely slower and more labor-intensive than electron microscopy. 

Can metagenomics replace electron microscopy?

 The answer is ‘‘no’’ again. For virus identification, metagenomics relies totally on known and identified genes and genomes, which, in turn, belong to viruses known and characterized by electron microscopy. In other terms, the vast majority of countless genes detected by metagenomics can be identified only to the extent as they belong to known sequences from known viruses. Further, metagenomics will not tell whether any detected sequences belong to complete, infectious virions or not. 

Can electron microscopy replace genomics?

 The answer is ‘‘yes,’’ but only when it comes to the identification of high-level taxonomic categories. Clearly, electron microscopy and genomics (or metagenomics) are not alternatives, but complementary. Both of them answer different questions and appear as different fingers of the same hand.

(Read more about bacteriophage here)