[jonmrodriguez]

Hehe funny that you mention phiX174 in the context of programming, that virus is amazing... Part of the reason phiX174 is so small is that it is "compressed" by having overlapping genes; in one area, three genes overlap in the same place! This is possible because there are 6 valid reading frames (direction and start point) for reading DNA: {forward or backward} x {address % 3 == 0, 1, or 2}.

In college I actually got to take part in refactoring that virus' genome into a decompressed version with no gene overlaps. And it worked! The decompressed version is still a functioning phage, and since there are no longer gene overlaps, future genetic engineers will have a much easier time modifying the phage as they see fit.

http://www.sciencedirect.com/science/article/pii/S0042682212...

[userbinator]

Overlapping instructions/data is something also commonly encountered in tiny demos (512b and below), e.g. http://meatfighter.com/puls/ and http://finalpatch.blogspot.ca/2014/06/dissecting-128-byte-ra...

I have no doubt that viruses of the computer kind also have made use of such techniques; and overlapping for obfuscation, not size-optimisation, is also a commonly seen trick in malware.

[corwinbad]

Why funny? biology is coding. 1,0 or A,T,G,C - all the same :-)

Get your genome compiler here: http://genomecompiler.com

[dnautics]

Hm, I used to work for Clyde Hutchison (and Ham Smith)... They told me that it didn't work when they made a naive decompression. Was there something they missed?

[jonmrodriguez]

Did their naive decompression make the genome longer? If so, it probably didn't fit in the capsid. In our version, we had to provide one of the genes (gene F) in a plasmid in the host cell, in order to reduce the length of the decompressed genome to fit inside the capsid. See this section of our paper:

[The naive] decompression added 909 nucleotides to the wild-type genome. We next addressed practical constraints arising from the length of DNA that can be physically packaged within a øX174 capsid without impacts to reproductive fitness. Previous work has shown that the length of a øX174 genome, when packaged in vitro, must be kept within a few percent of the 5386 nucleotide wild-type length in order to avoid any significant fitness decrease ( Aoyama and Hayashi, 1985). Similar results were shown in vivo ( Russell and Muller, 1984). To reduce the decompressed genome length we removed the first 916 nucleotides of gene F, encoding the coat protein ( Air et al., 1978). We chose gene F because a plasmid containing a restriction fragment encoding wild-type gene F was able to complement two conditional gene F mutations ( Avoort et al., 1983). Additionally, the gene F coding sequence is greater than the total of the combined increases needed to implement the øX174.1 genome design. The truncated gene F version of the decompressed genome was named øX174.1f. To complement øX174.1f when transformed into host cells we designed a medium copy vector expressing gene F under control of a rhamnose-inducible promoter ( Fig. S1).

[dnautics]

ah, ok, had no idea that the capsid was that sensitive to genome length! Thanks! So it really did compress it for a useful purpose.

[GuiA]

That's pretty amazing. I'm guessing DNA compactness is a survival advantage for viruses, and that's how this emerged? Is gene overlap common in other species?

[jonmrodriguez]

Gene overlap is extremely rare actually! When phiX174 was first discovered, some researchers wondered if such a complexly intertwined system could even have evolved naturally, or if it might suggest that the virus was hand-engineered: http://adsabs.harvard.edu/abs/1979Icar...38..148Y

[wamatt]

I would think the opposite may be true, given that compressed information tends to be more sensitive to error, than uncompressed.

[TazeTSchnitzel]

Redundancy helps resistance to error, yeah. This thing could be quite easily damaged in transmission.