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Phage communities in gut microbiomes show novel diversity-generating retroelement systems

Variation in nature is essential for survival in this dynamic and unpredictable world we live in. Variation in genetic sequence and subsequently structural variation of the translated protein, allows for elaborate competition between organisms in metabolization efficiencies, and ultimately, survival of the genome. This paper aimed to characterize patterns in sequence variation in complex systems by sequencing the microbiomes of 12 individuals (collectively 48 gigabases). The authors in this paper essentially defined hypervariable regions as those sequences generated which had multiple copies (for accuracy purposes) as well as high nucleotide diversity relative to an online database. They found that many sequences in human phage communities were diversity-generating-retroelements (DGR), which are most popularly seen in a Bordetella phage hypermutation system. The tail fiber gene that the phage uses to attach to its host is highly mutable for it needs to keep up with the variable surface proteins to which it attaches to. These outer membrane proteins of the host are differentially expressed according to environmental stimuli the bacterium encounters over its life cycle. Central to this hypermutation system used by the phage is a reverse transcriptase (RT). Novel sequences of tail fiber genes are made when a reserve copy of the tail fiber gene is transcribed into RNA, to which the RT somewhat sloppily reverse transcribes. This mutated sequence is then inserted into the original gene location, resulting in a tail fiber gene that can now bind to a novel substrate (hopefully a bacterium outer membrane protein).
Of the genes that were deemed to be part of this DGR system, many were involved in host attachment. However, six were not tail fiber genes at all but rather cadherins, invasins, and fibronectins. Although not verified in this paper these modified enzymes heretofore not seen in DGR systems, could possibly bind novel substrates relative to the given gene of origin (assuming these are functional transcripts). Furthermore, all of the genes identified in these DGR systems were of the IG-superfamily, which of course are also the genes used in somatic hypermutation (antibody diversification), possibly indicating a structural conservation nature has selected for rapid and novel protein production demands.
Exciting questions that come to mind are:
Who is using these genes?
What are phage doing with fibronectins, invasins, or cadherins?
Can these genes be (or possibly already have been) transferred horizontally to their bacterial host resulting in a bacterium which can now bind a novel substrate or assist in the metabolization of a new substrate?
 
 

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