Not sure what you’re getting at here, can you clarify? What does this have to do with temperature-dependent sex determination?

Something like a virus could be considered “efficient” in that it has a small genome because it hijacks host machinery to replicate, but it can’t be “self-contained” due to this reliance on a host.

But genuinely, what are you trying to say here?

Yes, this study makes the point better, although it's still small (n=8 homozygotes), and relies on retrospective analysis of clinic records.

Based on that study, it does look like there could be faster progression in homozygotes, although I don't know if there's enough data to argue that the normal allele is specifically conferring an advantage, as opposed to simply a dose effect of having 2 copies of the mutant allele.

It's also worth noting that not all studies show this same trend. For example, a 2019 Neurology study (https://n.neurology.org/content/neurology/92/18/e2101.full.pdf), which was somewhat larger (n=28 homozygotes) and used patients who are part of the EHDN Registry Database (ie using standardized data collection protocols for clinical data) did not see a difference in disease progression between homozygotes and heterozygotes.

> There are some disorders where the normal allele in heterozygotes confers some advantage, such as with Huntington's disease. Wexler, N. S., et al. (1987). Homozygotes for Huntington's disease. Nature, 326(6109), 194–197. https://doi.org/10.1038/326194a0

Just wanted to point out that this is a pretty outdated reference (from before the causative gene for HD was actually identified - they had a rough idea of the locus based on linkage analysis in HD families). As far as I am aware, there isn’t any strong evidence that the normal allele in heterozygotes confers an advantage in HD - and the article you linked actually states that homozygotes and heterozygotes appear to have the same phenotype, suggesting a true dominant condition, rather than one where heterozygosity is advantageous. There is a caveat that homozygotes for HD are quite rare, so studies involving them can be somewhat small.