Gene Manipulation Outcomes in Wild vs. Laboratory-Reared Animals

I had an interesting discussion recently and wondering if anyone knows of any references on this…A colleague has challenged the idea that the so-called longevity genes such as daf-2 (though this could probably apply to any gene/function) actually have any effect in a “true” wild-type background meaning in an animal taken from the wild. He mentioned some examples in Drosophila and said that the same was probably true of C. elegans. Specifically, that while perturbing these genes works great in laboratory-reared animals, if we were to take an animal from the wild and do the same experiments, it is debatable whether we would observe any effects, and if we did, they would be modest at best. I am wondering if anyone knows of any actual examples, specifically in C. elegans, but in other species too, where this has been tried? Just to be clear, not trying to step on anyones toes or questioning validity of well established studies, but am looking for examples of really any genes (though something like daf-2 or other genes that are associated with lifespan manipulation would be ideal for this particular discussion) where a gene was manipulated in an animal taken from the wild and showed the same phenotype as in a laboratory animal. Thanks.

Though not on the subject of daf mutants or lifespan, this paper from Matt Rockman’s lab might be of interest: https://elifesciences.org/content/4/e09178. Basically they sampled lots of wild strains and compared their phenotypes when treated with RNAi to essential embryonic genes, and found a tremendous amount of variation, only about half of which could be explained by variations in RNAi sensitivity. N2 appeared roughly average in this study (there were wild strains that had more severe phenotypes and others that had less severe phenotypes).

There are lots of takeaways from a study like this, but I guess what I’d say in response to your question is that in general, wild animals are heterogenous, and laboratory strains represent a random sample from that heterogenous pool. A priori, one would expect a laboratory strain (of C. elegans or any other animal) to be unusual in certain respects and fairly average in other respects, just by virtue of its having been chosen more or less at random. Of course, a strain like N2 has undergone selection and adaptation to the laboratory environment, which might make it more likely to be non-representative of wild populations with respect to some traits. I don’t think that this is an argument not to use laboratory strains, which have many other advantages - just something that one needs to keep in mind. It’s unfortunate that broad comparative studies (like the one I mentioned) are not more common, as they are really helpful in that regard.

What were the Drosophila examples? I’d imagine that in the wild, a daf-2 population would not do very well due to the boom and bust nature of the life cycle, requirement for fast population growth, appropriate dauer exit etc. But that is due to ecological/ selection factors rather than ageing, which I would argue is separate. Although I suppose you could argue that a rotting apple is unlikely to remain a bacterial haven for worms for 30 days, so you may be unlikely to see 30 day old daf-2 worms in the wild (how long do rotting apples last, and how many worms can they support?).

Anyway, there may be some correlation between longevity and insulin signalling in wild Homo sapiens. Here is a study I remember, there may be more recent ones, but I haven’t looked for some time http://www.pnas.org/content/105/9/3438.full
It remains to be shown if the same effect would have been seen in the stone age :slight_smile: - but again, I would argue that that would be due to ecological factors rather than ageing.

So perhaps ageing does not happen regularly in the wild (although if you bring wild strains into the lab, you may be able to see it). There’s an interesting quote from a slightly obscure paper from Leonard Hayflick, which I like for how dramatic it is:

“Humans have survived with a life expectation of twenty-five years or less for 99.9% of the several million years that we have been a species. No prehistoric human remains have been found to be older than about 50 years. If the time in which the human species has existed could be imagined on a twenty-four hour time scale, aging as a process that most people in developed countries experience would occur only a few seconds before midnight”

(although, given the time scale he may be referring to the Homo genus rather than Homo sapiens specifically…)
https://books.google.ca/books?id=Mb_azRnIBjsC&pg=PA1&lpg=PA1&dq=modulating+aging,longevity+determination+and+the+diseases+of+old+age&source=bl&ots=IGNxkuCqdD&sig=7Y8Ke_0MZz2Hk0fbegRKBw49RQk&hl=en&sa=X&ved=0ahUKEwium8Xu5-vOAhUDJCYKHeMrCc8Q6AEIGzAA#v=onepage&q&f=false

Thank you both for your insight. I completely agree - really wish there were more comparative studies that looked at the effects of manipulating genes across multiple species and genetic backgrounds. Mary Anne Felix gave an excellent talk on this latter point at the last worm meeting. I do not see it published yet though. Hopefully soon!

The Drosophila (and some non-Drosophila) references mentioned earlier are here:
http://www.evolutionary-ecology.com/abstracts/v03/1275.html
https://www.ncbi.nlm.nih.gov/pubmed/12882325
https://www.ncbi.nlm.nih.gov/pubmed/16701379
https://www.ncbi.nlm.nih.gov/pubmed/19324735

The daf-2 reference in C. elegans here:
http://www.ncbi.nlm.nih.gov/pubmed/15590605