Ardern, Swamidass, Gauger, and Overlapping Genes

[Mercer (John Mercer)]

@Zachary_Ardern

You may know that I work on overlapping genes, and am happy to say that I am one of very few experts on the topic. The truth is, as I see it, that they are highly surprising genetic constructs. In fact, it is very hard to tell how many there actually are, for various technical reasons which we are in the process of writing up.

I think that writing as though we don’t know much about overlapping genes until you write a paper is offensive.

@Zachary_Ardern

There are a lot of unanswered questions in this area. I am working hard to answer some of them, with my students and other group members.

Adding this without mentioning all of the work already done and published by others is offensive, too.

@Zachary_Ardern

She is saying that it doesn’t look like the way a human would design it, because we don’t design messages inside messages. That is too sophisticated for us. Therefore it requires a design genius.

I don’t see any difference between that and Josh’s characterization.

@Zachary_Ardern

We also don’t know the proportion of protein sequence space which is functional, or folds, or whatever criterion someone may want.

We do. For specific enzymatic activities. It’s routinely more than one in 10^8 - 10^9. “Folds” is meaningless in this context, as every random protein folds, and there is no one-to-one correspondence between functions and folds.

@Zachary_Ardern

We just have a few estimates, some of which are disputed or disputable, using extremely different methods and testing different things.

We have many more than a few. The hundreds we have from catalytic antibodies alone are far more than a few.

Abzyme - Search Results - PubMed

Then there are many others.

@Zachary_Ardern

These are difficult questions, and I am very familiar with the literature on them, and have heard many talks by leading experts who believe that functional proteins are very rare in sequence space.

I find that hard to accept. Scientists cite the relevant data; they don’t use hearsay as you are doing.

Cite the data instead of making an assertion from a questionably authoritative position, please.

@Zachary_Ardern

Firstly, because there are good biophysical reasons to doubt that folded proteins are common in sequence space (I suspect that overlapping proteins don’t adopt a highly specified fold…

The term “highly specified fold” is nonsensical. Folds are structural classifications of proteins. They don’t correspond to functions, as Ann Gauger claims.