Cameron Redpath will make his Scotland debut in the opening Six Nations match against England, having previously represented the defending champions at youth level.
The Bath centre will line up outside Finn Russell, who missed the Autumn Nations Cup with a shoulder injury.
George Turner starts at hooker in the absence of Fraser Brown and Stuart McInally to injury.
Scotland are aiming for a first win at Twickenham since 1983.
Redpath, son of former Scotland captain Bryan, had previously been called into the England set-up by Eddie Jones without winning a cap, but elected to play for Scotland.
He will line up opposite his former England under-20 team-mate Ollie Lawrence, also making his first Six Nations start, while Chris Harris continues at outside centre for Scotland.
"It's always a pleasure to welcome a new player into our squad and we are looking forward to Cam Redpath winning his first cap on Saturday," head coach Gregor Townsend said.
"We have been really impressed with Cam's contributions in the time he has been with us in camp."
Townsend picks a familiar forward pack, with Matt Fagerson given the nod at number eight and Scott Cummings and Jonny Gray starting in the second-row.
In-form Newcastle back-row Gary Graham is poised to win his third cap from the bench, while there is also a return to the matchday squad for Richie Gray.
Edinburgh hooker Dave Cherry could make his debut as a substitute.
To mark the 150th anniversary of the first rugby international between the sides, each starting Scotland player will have the corresponding name from the 1871 team embroidered onto their shirt.