Head coach Vern Cotter revealed his 32-man squad on Tuesday, handing chances to scrum-half Sam Hidalgo-Clyne, forwards Ben Toolis and Hugh Blake and back-row Hamish Watson.
All four are in their early 20s and Cotter said they had shown the right attitude for their club side.
"They have impressed me with their desire to go forward," Cotter told the BBC. "They reflect the Scottish spirit of attacking and leading, to develop into impressive performers."
In total, 11 players from the capital club are selected, including stand-off Greig Tonks, whose only previous appearance for Scotland came as full-back against Samoa in 2013.
Centre Matt Scott, who missed last year's summer tour and the Autumn internationals with shoulder and hand injuries respectively, also returns.
Scotland begin their Six Nations campaign in France on Feb. 7.
Squad:
Forwards: Hugh Blake, Fraser Brown, Blair Cowan, Geoff Cross, David Denton, Alasdair Dickinson, Jonny Gray, Richie Gray, Ross Ford, Jim Hamilton, Rob Harley, Euan Murray, Gordon Reid, Alasdair Strokosch, Ben Toolis, Hamish Watson, Jon Welsh.
Backs: Mark Bennett, Sam Hidalgo-Clyne, Alex Dunbar, Dougie Fife, Stuart Hogg, Peter Horne, Greig Laidlaw, Sean Lamont, Sean Maitland, Henry Pyrgos, Finn Russell, Matt Scott, Tommy Seymour, Greig Tonks, Tim Visser.
(Reporting by Martyn Herman, editing by Pritha Sarkar)
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