We can’t be totally confident. I’d guess that if you did a sensitive test of fitness (you’d need a big fish tank and a lot of time) you’d find the human sequence didn’t rescue the deletion perfectly. They’ve done this recently in c elegans—looking at long term survival in the population level, and they find a huge number of apparantly harmless mutations are very detrimental at the population level.
The reason I’d say it was unlikely is just that spacers of that kind aren’t common (I don’t know of any that aren’t inside genes). If there were to sequences on either side that needed to bend around to eachother to make contact, it could be plausible, but since they selected by epigenetic marks, rather than sequence conservation, it would be odd and novel if they’d managed to perfectly delete such a spacer (actually it would be very interesting of itself.)
I think you are being confused by two things
1) The mutation I said they made was deliberately targeted to a splice site, which are constrained (though you can’t use them to identify sequences because they are very small, and so occur randomly outside functional sequence all the time)
2) You are thinking too simplistically about sequence constraint. RNA folds by wrapping up and forming helices with itself, so the effect of a mutation is dependent on the rest of the sequence. Each mutation releases constraint on other base pairs, and introduces it to others. So as this sequence wanders through sequence space it does so in a way that preserves relationships, not absolute sequence. From it’s current position in sequence space, many mutations would be detrimental. But those residues may get the chance to mutate later on, when other residues have relieved them. This applies to proteins as well by the way. Proteins are far more conserved in 3d shape than in 2d sequence.
We can’t be totally confident. I’d guess that if you did a sensitive test of fitness (you’d need a big fish tank and a lot of time) you’d find the human sequence didn’t rescue the deletion perfectly. They’ve done this recently in c elegans—looking at long term survival in the population level, and they find a huge number of apparantly harmless mutations are very detrimental at the population level.
The reason I’d say it was unlikely is just that spacers of that kind aren’t common (I don’t know of any that aren’t inside genes). If there were to sequences on either side that needed to bend around to eachother to make contact, it could be plausible, but since they selected by epigenetic marks, rather than sequence conservation, it would be odd and novel if they’d managed to perfectly delete such a spacer (actually it would be very interesting of itself.)
I think you are being confused by two things 1) The mutation I said they made was deliberately targeted to a splice site, which are constrained (though you can’t use them to identify sequences because they are very small, and so occur randomly outside functional sequence all the time) 2) You are thinking too simplistically about sequence constraint. RNA folds by wrapping up and forming helices with itself, so the effect of a mutation is dependent on the rest of the sequence. Each mutation releases constraint on other base pairs, and introduces it to others. So as this sequence wanders through sequence space it does so in a way that preserves relationships, not absolute sequence. From it’s current position in sequence space, many mutations would be detrimental. But those residues may get the chance to mutate later on, when other residues have relieved them. This applies to proteins as well by the way. Proteins are far more conserved in 3d shape than in 2d sequence.