Using Hornady's Ballistic Calculator and comparing a 22 Dasher launching the Hornady 53 grain bullet at 4000 fps (impressive .290 BC) to a 20 Practical and 40 grain Horandy at 3800 FPS there is not a major advantage burning the extra powder if you just consider drop and drift. Where the Dasher has a significant advantage is energy. Using that large of cartridge on squirrels is overkill for high volume situations in my opinion but for larger targets (prairie dogs and up) or lower volume shooting it would be worth it for the added killing power. See comparisons below. Drift is based on 10 mph, 90 degree crosswind; sea level, 59 degrees.
400yd Drop/Drift/Energy 500 yd Drop/Drift/Energy
22 Dasher, 53 gn Hornady @ 4000 fps -14.6"/13.4"/778 ftlb -28.6"/22"/611 ftlb
20 Practical, 40 gn Hornady @ 3800 fps -17.2"/15.2"/497 ftlb -33.7"/25.2"/381 ftlb
The Dasher has almost as much energy at 400 yards as the Practical does at 200 yards. I have to say I have hit squirrels at 400+ yards with the Practical and they still take it hard, sometimes launching in the air. Not really any crawl offs with 500 ft lbs of energy!
I do not have any first hand experience with something like the 22 Dasher but have been considering a hot rod varmint gun. Truth is I will likely only hunt PD's once a year as there are none within 12 hour drive and I get lots of premium, big volume shooting at ground squirrels in Nor Cal but at times you just want more!
For those of you that shoot the 22 Dasher or similar with 50-55 gn bullet how is the recoil for seeing your hits? That is big deal to me. If I build one I would definitely have a muzzle brake on it.
FYI....for the ELD bullets Hornady has a new, more sophiticated ballistics calculator called 4DOF:
http://www.hornady.com/ballistics-resource/4dof