Eli5: How do we know which genes do what, and what about combinations and power of expression?

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Eli5: How do we know which genes do what, and what about combinations and power of expression?

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Anonymous 0 Comments

We are gathering knowledge on that since the 1950s.
There were several methods. One idea is that you randomly destroy genes by x-ray and then select phenotypes. Such work was done even before we could sequence genes, and gave the knowledge of what goes wrong if a gene is missing.
Gene interactions were discovered by crossong those mutants.

Another approach was to look at things at the protein level. You could extract protein from the organism and compare the amounts (too little, too much). Protein interactions could be discovered by using one protein as a hook and fish out everything that binds to it.

There were methods to stain proteins and do the staining in situ (within the cell) so you can tell where exactly it is.

There were methods to crystallize a protein and determine its 3D structure. Then compare 3D structures, organize them into families, and based on knowledge of one family member, guess the function of another. (And of course test the guess.)

Once you could sequence and synthesize DNA, a whole bunch of methods came up. You could now inject a gene and look what it does. You could now exactly tell what protein comes from a gene. It sometimes turned out that a gene has 2 names because people thought they were two different things.

Then RNA chips came in, and you saw mass data on expression. Whole genome sequencing. Single cell sequencing. Nowadays everything about the whole proteome, genome, etc interaction, and it is mostly done with computers.

So in old days they had painstakingly lot of work to isolate one single protein, and asked all possible questions about it. What’s the size? What’s the charge? What are the interaction partners? What if I inject it into a fertilized drosophila egg?

Nowadays they work a lot on huge databases of all knowledge and how to squeeze out some meaningful information.

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