Stuart Hogg will captain Scotland for the first time when they take on the USA in Houston.
Dark Blues head coach Gregor Townsend has named a revamped starting XV following last weekend's 48-10 win over Canada - with seven players set to win their first caps.
Hogg's Glasgow teammates Matt Fagerson and George Horne will make their international bows alongside their elder brothers, with back-rower Fagerson joined by prop Zander and halfback Horne lining up alongside inside centre Pete.
There will also be debuts for the Glasgow trio Jamie Bhatti, George Turner and Adam Hastings, as well as Edinburgh's Lewis Carmichael and Luke Hamilton.
"We always planned to play as much of the squad as possible on this tour, and we also deliberately picked more Edinburgh players in the first game because their season finished earlier," Townsend - who has changed all but three of the side that thrashed the Canadians in Edmonton last weekend - said.
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"Now we welcome most of the Glasgow Warriors contingent into the team. On top of that there are seven players making their first starts for the country, which is really exciting, and we are looking forward to them going out and grabbing this opportunity."
The Edinburgh pair of Ben Toolis and Blair Kinghorn as well as Sale wing Byron McGuigan are the only players to retain their places at the home of Major League Soccer outfit Houston Dynamos.
Saturday's match will be only the eighth time in close to 700 Scotland Tests when two sets of brothers have been on the field at the same time.
