exon shuffling.md

(I paid Tegan to spend an hour or two writing these notes)

Exon-shuffling

It’s definitely true that multiple exons can be attached to produce a novel protein; It’s definitely not the case that all novel genes were produced by exon-shuffling. Exon-shuffling was not a thing for prokaryotes, and didn’t get popular with eukaryotes until metazoans, where they got wildly popular. This is probably in connection with multicellularity, since most of the proteins produced with exon-shuffling have an extracellular role. Also, the modules that end up in these proteins are mostly the ones that are able to fold properly on their own and are structurally stable. I have a weak sense that cellular proteins are largely conserved from early evolution, ie weren’t created with exon-shuffling, and they’re definitely slower to evolve. Fun fact: “most of the modular proteins were assembled from some five-dozen class 1-1 modules.” (Class 1-1 means the exons were between 2 phase 1 introns.) I don’t yet have a sense of the relation between ancient protein exons and modular exons.

Links:

https://www.sciencedirect.com/science/article/pii/S0378111999002280?via%3Dihub

• This was the most useful link I found, and most of the info above is from this link.
• "Obviously, such basic structural units were invented independently several times during evolution (Patthy 1991a)"
• "modular proteins produced by exon-shuffling were defined as those which contain at least one of the modules spread by exon-shuffling and this module is joined to at least another protein-domain. Note that according to this definition, a protein consisting of a single module and a membrane anchoring segment and/or signal peptide is not counted as a modular protein, but is considered to represent the protomodule stage of the modularization pathway (Patthy, 1994, 1995, 1999)"
• "the modules used most frequently in the construction of modular proteins are not random representatives of the protein universe ... about half of the non-homologous protein families belong to the alpha-beta class, 25% belong to the mainly alpha class, about another 25% is mainly beta. Structural classification of the class 1-1 modules shows a significantly different distribution: more than 60% belong to the mainly beta class and only about 10% are mainly alpha"
• "It seems probable that the rise of exon-shuffling has contributed significantly to this accelerated evolution of metazoa."

https://www.sciencedirect.com/science/article/pii/B0122270800012295

• “Why are eukaryotic genes split? One theory is that exons are the primary unit of protein evolution. According to this theory new genes emerge during evolution by exon shuffling, which occurs by a process called DNA recombination. Thus, two genes with multiple exons could recombine to generate a new gene containing exons from both genes. When the new gene is transcribed and spliced, a novel protein would be produced. Another theory is that the split gene organization evolved because it provides an efficient means of producing multiple proteins from a single gene by alternative splicing.”

https://en.wikipedia.org/wiki/Exon_shuffling

http://science.sciencemag.org/content/250/4986/1377

• “If genes have been assembled from exon subunits, the frequency with which exons are reused leads to an estimate of the size of the underlying exon universe. An exon database was constructed from available protein sequences, and homologous exons were identified on the basis of amino acid identity; statistically significant matches were determined by Monte Carlo methods. It is estimated that only 1000 to 7000 exons were needed to construct all proteins.”

https://www.ncbi.nlm.nih.gov/pubmed/22948334

• Evolutionary history of exon shuffling

Lots of things written by this guy:

https://scholar.google.com/citations?user=_JGHDj8AAAAJ&hl=en&oi=sra

https://www.sciencedirect.com/science/article/pii/S0945053X96901316

• “Although exon shuffling is the most efficient way of constructing modular proteins, recent studies on the evolution of multidomain proteins of prokaryotes emphasize that intronic recombination is not an absolute prerequisite of module exchange.”