Glasgow hooker Fraser Brown has been given the nod to start in place of centurion Ross Ford for Scotland's opening RBS 6 Nations clash with Ireland.
Edinburgh front-rower Ford has been a mainstay of the Dark Blues line-up for more than a decade.
But his omission is one of three changes to Vern Cotter's team from November's win over Georgia, with number eight Josh Strauss taking over from Glasgow colleague Rob Harley while centre Huw Jones returns in place of Mark Bennett.
The return of Jones from a foot injury is a boost for the hosts ahead of Saturday's Murrayfield clash.
The Stormers midfielder made a swift impact when he became the first Scot to score a try double against Australia in his first start for the national side during the autumn Tests but was injured a week later against Argentina.
He will rekindle the centre partnership he forged in those two Tests with Alex Dunbar in between returning half-backs Greig Laidlaw and Finn Russell, and the back-three trio of Stuart Hogg, Sean Maitland and Tommy Seymour, who contributed half of Scotland's 10-try tally in the autumn.
Strauss' inclusion sees Ryan Wilson make a positional switch to the blindside of the back-row, with Hamish Watson holding down the openside role he occupied throughout the autumn.
Second-row brothers Jonny and Richie Gray return to the boiler house with young props Allan Dell and Zander Fagerson packing down either side of Brown in the front-row.
Scotland head coach Vern Cotter said: "Although it's a reasonably settled squad, it's nice to have an uncapped player and some reasonably new players in the team, who bring their enthusiasm along with the others.
"We've been growing our depth and our versatility within that, so we have a number of different options that allow us to continually attack the opposition, which is our main focus."
He added: "Facing Ireland first up doesn't get much harder.
"They are at the top of their game and will come here with confidence after beating some of the best teams in the world, including the All Blacks and Wallabies and having won the tournament twice in the past three years."
There are four further changes to the bench, with Edinburgh tighthead Simon Berghan in line for a test debut if called upon from the replacements.
Elsewhere Tim Swinson, Duncan Weir and Bennett occupy the remaining back replacement spots in place of Grant Gilchrist and injured Warriors pair Pete Horne and Rory Hughes.
"We aim to win every game we play but know that Ireland will come here with a lot of confidence and try to dominate us on our home paddock," added Cotter.
"Those are the challenges of the sport at a high level but we'll embrace that and put everything we have into getting the right performance and result this Saturday."
Live Six Nations coverage of Scotland versus Ireland on RTÉ Two from 1.30pm on Saturday (KO 2.25pm) and live radio commentary on RTÉ Radio 1’s Saturday Sport programme from 2pm.
Live coverage of Scotland v Ireland in the Women’s Six Nations on RTÉ Two from 6.30pm (KO 6.35pm) on RTÉ 2, with live radio updates and reaction on an extended 2FM Game On programme at 7pm.
Live coverage of Scotland v Ireland in the U20's Six Nations on RTÉ Two from 8.15pm (KO 8.30pm)