Key Discoveries in the History of Science

[Swammerdami]

I stumbled on a Youtube about "giruses" ( Giant viruses), which I'd never heard of before. Whereas typical viruses have a dozen genes or fewer, a girus may have a thousand genes; and some, perhaps, have their own metabolism. They still need a living cell to reproduce, but once installed can subvert that cell more thoroughly than ordinary viruses can.

Also discovered are virophages — tiny viruses which target giruses rather than living cells, though again reproduction must wait until the girus infects a living cell. (For example, the Sputnik I virophage invades a mamovirus, which in turn targets an amoeba.) One type of virophage subverts the girus to reproduce virophages instead of giruses. Another type installs itself into the daughter giruses, which then produce more virophages in future.

Some giruses have defenses against virophage invasion; virophages have evolved to break down those defenses. Some protists have incorporated virophage DNA and respond to a girus invasion by producing virophages to attack giruses.

Giruses may account for some lateral gene transfers in living cells.

Wow! I already knew that life was incredibly complicated, and it just got more so!

 

[Swammerdami]

RNA translation

I didn't study biology in school, but after reading Life on the Edge by Al-Khalili and McFadden and a couple of books by Nick Lane. I've become fascinated by the low-level details of life and life's origin.

The most complex "machine" in LUCA (most recent universal common ancestor of all life) is the ribosome — the machine which translates the gene sequence in mRNA into a protein. IIUC LUCA's ribosome was fairly similar to the ribosomes in advanced life like vertebrates. A vertebrate cell can contain up to 10 million ribosomes. One-quarter of the mass of an E.coli cell is taken up by ribosomes; they consume about 50% of that cell's energy, when the cell is growing.

There are animations on YouTube that show how a ribosome works: the small subunit attaches to a Start codon; the large subunit attaches to that activated small subunit, leaving a big cavity inside where tRNA's do the work. These tRNA's pass through the ribosome, each one attaching an amino acid to a growing protein. It seems so complicated it's almost enough to make one believe in intelligent design!

In the most primitive proto-life, there may have been a simple chemical relationship between nucleotide pairs or triplets and amino acids, but by now the "genetic code" is crystalized into specific tRNA's which are part of the genome (across life there are tiny differences in the genetic code, especially in mitochondria). Since there are 4³ = 64 different RNA codons, it would seem that there should be at most 64 distinct tRNAs but I just read that, so far inexplicably, there are over 100.

The tRNAs themselves are rather bizarre molecules, with some nucleotide sequences repeated (but reversed and anti-sense) so the tRNA can couple to itself, forming a secondary cloverleaf shape. The molecule then tangles up into a tertiary "Florida shape." One of the uridine nucleosides is replaced with Pseudouridine — Don't ask me why!

During translation, nucleotides are read in groups (codons) of three. What controls the alignment? Couldn't you have an adjacent codon pair like (UCA)(UGC) coding for (Serine)(Cysteine) but with the three underlined nucleotides (AUG, forming a Start codon) being grabbed by the Ribosome small subunit, thereby causing misalignment and producing a useless "protein"?

There are mechanisms to destroy accidentally created proteins, but I now read that  Ribosomal frameshift is employed "deliberately" by some viruses. Via such shifting two different useful proteins can be generated from the same stretch of RNA. Two proteins for the (genomic) price of one!

Then just today I read about investment in tRNA therapy! Many genetic diseases are caused by a mutation of CGA (Arginine) to UGA (Stop). When the ribosome encounters the UGA it terminates the protein it's constructing. Several different genetic diseases would be cured with an engineered tRNA which treats the UGA (Stop) as CGA (Arginine); and indeed that's the plan!

It may seem far-fetched — after all, most of the UGA's that ribosomes encounter will be legitimate Stop codons, but there's much redundancy. (There seem to be natural tRNA's competing for the same codon — see above — and useless proteins get recycled.) Researchers and investors are hopeful.

I'm not qualified to comment on any of this, but it seems fascinating so I try to share.