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Sione Tuipulotu will captain Scotland in the autumn Tests against South Africa, Australia, Fiji and Portugal while his brother Mosese has been called up for the first time.
There are also recalls for prop D'Arcy Rae, centre Rory Hutchinson and winger Darcy Graham, who has been missing through injury since the 2023 World Cup.
Glasgow's New Zealand-born fly-half Tom Jordan has recently become eligible and his inclusion nudges Ben Healy out of the 45-man squad.
Alex Samuel, Ben Muncaster and Freddy Douglas - who has yet to feature in the United Rugby Championship for Edinburgh - are the other uncapped players chosen by head coach Gregor Townsend.
Finn Russell and Rory Darge were co-captains for the Six Nations and are listed as vice-captains for the November matches.
Experienced locks Jonny and Richie Gray are not selected, with hooker Johnny Matthews plus back-row forwards Hamish Watson and Magnus Bradbury also overlooked.
Sam Skinner, Andy Christie, Cameron Redpath and Kyle Steyn are among those missing through injury.
Players based in England and France will not be available for the opening match against Fiji on 2 November as it falls outside the international window.
World champions South Africa visit Murrayfield eight days later, with the Portugal game on 16 November and the match against Australia on 24 November.
Australia-born Sione Tuipulotu - who qualifies for Scotland through his grandmother from Greenock - has earned 27 caps since joining Glasgow Warriors in 2021.
Younger brother Mosese, who also plays at centre, moved to Edinburgh this summer.
"Sione has been one of our key leaders over the last couple of years and thrives in that leadership role," explained Townsend.
"We've seen that in his outings as Glasgow captain and when he had the opportunity to lead the team against Chile a few months ago.
"He often sets the emotional tone and mindset required for the team and he also contributes significantly to both our attack and defence.
"Last season we looked to deepen our leadership group and we now have a number of people who could step up as captain.
"Sione is aware that he will have leaders around him to offer support and share the leadership responsibilities needed throughout the week and during the game."
Forwards: Ewan Ashman (Edinburgh), Josh Bayliss (Bath), Jamie Bhatti, Gregor Brown, Scott Cummings (all Glasgow Warriors), Luke Crosbie (Edinburgh), Alex Craig (Scarlets), Rory Darge, Jack Dempsey (both Glasgow Warriors), Freddy Douglas (Edinburgh), Matt Fagerson, Zander Fagerson (both Glasgow Warriors), Grant Gilchrist, Patrick Harrison (both Edinburgh Rugby), Will Hurd (Leicester), Ewan Johnson (Oyonnax), Nathan McBeth, Elliot Millar Mills (Northampton), Ben Muncaster (Edinburgh), D'Arcy Rae (Edinburgh), Dylan Richardson (Sharks), Jamie Richie (Edinburgh), Alex Samuel (Glasgow Warriors), Pierre Schoeman (Edinburgh), Rory Sutherland, Max Williamson (both Glasgow Warriors)
Backs: Matt Currie (Edinburgh), Jamie Dobie (Glasgow Warriors), Darcy Graham (Edinburgh), Adam Hastings, George Horne (both Glasgow Warriors), Rory Hutchinson (Northampton), Huw Jones, Tom Jordan (both Glasgow Warriors), Blair Kinghorn (Toulouse), Stafford McDowall (Glasgow Warriors), Harry Paterson, Ali Price (Edinburgh), Arron Reed (Sale Sharks), Kyle Rowe (Glasgow Warriors), Finn Russell (Bath), Mosese Tuipulotu (Edinburgh), Sione Tuipulotu, captain (Glasgow Warriors), Duhan van der Merwe (Edinburgh), Ben White (Toulon)