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Wolbachia the Holy Grail - Now go away or I will taunt you a second time

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*update: Seth Bordenstein let me know that they DID codon optimize their constructs. The text below reflects this change. **update, part 2: below I note some comments ( in blue ) as a result of interactions with lead author John Beckmann via the twitter. He was kind enough to participate in a long public and then private exchange - thanks to him. This morning I was pleased to see that J ohn Beckmann's manuscript describing some enzymatic functional activity of candidate CI genes was just made available on the Nature Microbiology page.  So, today, we will dive again into the world of CI-inducing loci and explore what this manuscript can tell us about the mechanisms behind CI and what these two proteins might do in the insects. Beckmann et al start out with a different premise from that of Le Page et al.  in that John had already identified two candidates, wPa_0282 and wPa_0283, from another study, which focused on proteins found in Wolbachia -modified mosquito sperm. They state

The Wolbachia "holy grail"

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The once-obscure alpha-proteobacterium Wolbachia pipientis, was catapulted into medical relevance by the discovery that it inhibits the replication of RNA viruses .  However, it was first discovered for its odd quirk of manipulating insect reproduction . That's right, Wolbachia were called "reproductive parasites" and for a long time, no fitness benefit was attributed to them.  These intracellular masters do things like kill male offspring, feminize male offspring, induce parthenogenesis, and the most common phenotype, sperm-egg incompatibility (also known by its more complicated name: cytoplasmic incompatibility or CI) (Figure 1).   Figure 1. Modified from Werren et al., 2008 .  Wolbachia cause four distinct reproductive phenotypes in a range of arthropod orders (top).  The mechanisms behind CI - meaning how does  Wolbachia  induce it -  have been a mystery for some time.   When you make a cross between infected males and uninfected  Nasonia  females, unviable em