Sam Johnson will make his Scotland debut in their Six Nations opener against Italy on Saturday at Murrayfield.
The Glasgow Warriors centre is one of three uncapped players in the squad - hooker Jake Kerr (Leicester) and back row man Gary Graham (Newcastle) are both among the replacements.
Scotland have made six changes to the side who defeated Argentina in their last international back in November.
Johnson comes into the midfield, with Finn Russell reverting to fly-half and Adam Hastings dropping to the bench, while Tommy Seymour replaces the injured Sean Maitland on the wing.
And with Edinburgh resurgent under Richard Cockerill this season, Scotland head coach Gregor Townsend has chosen to go with the capital outfit's tight five.
Hooker Stuart McInally will pack down in between props Allan Dell and WP Nel, with Ben Toolis and Grant Gilchrist forming the second row.
Exeter lock Sam Skinner will slot into the back-row after showing he can fill in at flanker during his impressive introduction during the autumn, and he will have Ryan Wilson and Jamie Ritchie alongside him.
Fraser Brown, Jonny Gray and Hamish Watson miss out due to injury while Josh Strauss is among the replacements.
Skipper Greig Laidlaw will partner Russell in the half-backs, while Australia-born Johnson - who qualifies on residency grounds after signing for Glasgow in 2015 - lines-up alongside Huw Jones in midfield.
Edinburgh full-back Blair Kinghorn will start on the left wing opposite Seymour, and Stuart Hogg will again provide an attacking threat from full-back.
Scotland Head Coach Gregor Townsend said: "Italy have made life tough for Scotland in every Test match we've played.
"I remember that as a player, as a supporter and as a coach - and they were better than us in most of last season's contest in Rome. They played with pace, were physical and we had to play really, really well in the final quarter to win.
"That performance and also the recent displays of Benetton Treviso are sharp reminders for our players that this will be a difficult fixture.
"Our challenge is to win the physical battle, which is a strength of Italian rugby."
Scotland: 15 Stuart Hogg, 14 Tommy Seymour, 13 Huw Jones, 12 Sam Johnson, 11 Blair Kinghorn, 10 Finn Russell, 9 Greig Laidlaw (captain); 1 Allan Dell, 2 Stuart McInally, 3 Willem Nel, 4 Ben Toolis, 5 Grant Gilchrist, 6 Sam Skinner, 7 Jamie Ritchie, 8 Ryan Wilson.
Replacements: 16 Jake Kerr, 17 Jamie Bhatti, 18 Simon Berghan, 19 Gary Graham, 20 Josh Strauss, 21 Ali Price, 22 Adam Hastings, 23 Chris Harris.