How much of the genotype-phenotype map do we understand in HIV?

Question

From what I understand, viruses have very small genomes relative to those of standard model organisms used in biological research. For example, according to Wikipedia, "the HIV genome contains nine genes that encode fifteen viral proteins". This is several orders of magnitude below the complexity of the mouse genome for example, with over 20,000 genes encoding over 50,000 proteins.

As a bioinformatics student (from a non-biological background) working with mammalian genomes, I often find the link between genotype and phenotype quite abstract and I'm unable to fully get an intuition for concretely how genomes can encode the instructions (or recipe using Dawkins' analogy) for creating complex phenotypes.

With this in mind, I wondered whether viruses, in particular HIV, which I know has been well studied, provide the simplest models for understanding the principles of how genes can encode the complete phenotypes of a functioning biological entity. Having such a small number of genes, I assume it is feasible to follow the transcription, translation and interaction of all genes and proteins? If so, is it the case that we understand how all of the genes and proteins work in HIV? If not, what is the main barrier in our understanding?

Apologies for this poorly-defined question. I am having a hard time getting my head around how molecular/cellular biology fits in with the complex phenotypes I've been studying in developmental biology/physiology and hoped that a simpler species/biological system could help to illuminate how it all comes together! Any pointers to further resources would be much appreciated.

Answer 1

I'm sure HIV is well studied since as you know it has a small genome and is highly relevent to therapeutic research, but virus regulation can be complicated and not representative of what happens in normal cells. This is why model organisms exist. The yeast Saccharomyces cerevisiae has about 6,000 genes and researchers have systematically deleted nearly every gene and looked at what happens to the cell. This information is available on the saccharomyces genome database. For example if you search SNF1 (which has a human homolog) on SGD (https://www.yeastgenome.org/locus/S000002885). You can see the phenotypes associated with deletion, overexpression, as well as a summary of what it does and how it's regulated (with original references). I don't think it gets any better than that. A lot of what is known about genetics and molecular biology comes from studies in yeast so I think it is worthwhile learning about yeast genetics to get a better understanding of what goes on in cells.