Winger Lee Jones will win his first international cap in Scotland's Six Nations opener against England at Murrayfield on Saturday.
And Edinburgh team-mate David Denton makes his first start in the back-row, alongside Ross Rennie and Al Strokosch.
The number 10 jersey, subject of much debate among Scottish supporters, will be filled by Dan Parks, with Chris Cusiter given the nod at scrum-half.
Ross Ford makes up the front row with Allan Jacobsen and Euan Murray.
With hooker Ford taking over the captaincy, World Cup skipper Al Kellock drops to the replacements' bench, with Jim Hamilton and Richie Gray the preferred second row pairing.
Glasgow-bound Sean Lamont and Edinburgh's Nick De Luca are the centres, with the latter coming in for the injured Joe Ansbro.
Max Evans plays on the opposite wing to Jones, with Rory Lamont at full-back.
Joining Kellock on the bench are Scott Lawson, Geoff Cross, John Barclay, Mike Blair, Greig Laidlaw and Graeme Morrison.
Jones, 23, has represented Scotland at A level and played international sevens.
He and 21-year-old Denton, capped once as a replacement against Ireland in a World Cup warm-up game, have been instrumental in Edinburgh's fine form in Europe this season.
Head coach Andy Robinson praised Jones, saying: "I've been pleased with the consistency he has shown and he fully deserves to win his first cap."
Robinson also stressed that the form of the two pro teams had influenced his selection.
"Edinburgh's qualification for the Heineken Cup quarter-finals and Glasgow's performances in the RaboDirect PRO12 mean that competition for places has intensified, particularly in the back-row," he said.
"We have experienced players in our team and they must make that knowledge count by helping the team to a successful start.
"It is not by accident that these games are referred to as test matches - because that is what they are, the ultimate in physical and mental challenge and that is certainly always on the menu when England are our opponents."
Scotland: Rory Lamont, Lee Jones, Nick De Luca, Sean Lamont, Max Evans, Dan Parks, Chris Cusiter; David Denton, Ross Rennie, Alasdair Strokosch, Jim Hamilton, Richie Gray, Euan Murray, Ross Ford (captain), Allan Jacobsen. Replacements: Scott Lawson, Geoff Cross, Alastair Kellock, John Barclay, Mike Blair, Greig Laidlaw, Graeme Morrison.