George Furbank is a surprise England starter with Freddie Steward dropped for the Calcutta Cup clash against Scotland.
Furbank is preferred to Steward at full back, with Ollie Lawrence returning to the side from injury for the Six Nations round three fixture.
George Martin is also back in the matchday squad on the bench, while Danny Care wins his 99th England cap as the starting scrum half, but there is no place for a fit-again Manu Tuilagi.
Props Ellis Genge and Dan Cole swap into the starting side instead of Joe Marler and Will Stuart, who drop to the bench.
“We’re pleased with the start we’ve made to our Six Nations campaign but know that a difficult test awaits us in Edinburgh against an in-form Scotland team,” said Borthwick.
“The atmosphere is always special for any Calcutta Cup match and I’m sure this weekend’s game at Murrayfield will be no different.
“This group of players are looking forward to the challenge on Saturday and to creating some very special memories.”
Furbank has had an outstanding season for Northampton, captaining Saints in the absence of Lewis Ludlam with the club currently top of the Premiership table. He was also part of the last England side to beat Scotland, winning a second cap at Murrayfield on a victorious trip north in 2020.
Lawrence’s return is timely with England seeking a ball-carrying focal point in their backline.
It was feared that the Bath centre could miss round three, but made a strong recovery from injury and earns immediate inclusion.
He is preferred to Tuilagi and Fraser Dingwall, who started the first two games of the tournament alongside Slade, with Furbank offering an extra pair of distributing hands in the backfield.
Martin, meanwhile, offers a punchy skillset as a replacement back-five forward, with the Leicester man capable of playing in the second row or on the blindside.
England team to face Scotland at Murrayfield (4.45pm GMT, Saturday 24 February)
15. George Furbank (Northampton Saints, 6 caps)
14. Tommy Freeman (Northampton Saints, 5 caps)
13. Henry Slade (Exeter Chiefs, 59 caps)
12. Ollie Lawrence (Bath Rugby, 21 caps)
11. Elliot Daly (Saracens, 66 caps)
10. George Ford (Sale Sharks, 93 caps)
9. Danny Care (Harlequins, 98 caps)
1. Ellis Genge (Bristol Bears, 59 caps)
2. Jamie George (Saracens, 87 caps) – captain
3. Dan Cole (Leicester Tigers, 109 caps)
4. Maro Itoje (Saracens, 78 caps)
5. Ollie Chessum (Leicester Tigers, 20 caps)
6. Ethan Roots (Exeter Chiefs, 2 caps)
7. Sam Underhill (Bath Rugby, 32 caps)
8. Ben Earl (Saracens, 27 caps)
Replacements:
16. Theo Dan (Saracens, 9 caps)
17. Joe Marler (Harlequins, 90 caps)
18. Will Stuart (Bath Rugby, 35 caps)
19. George Martin (Leicester Tigers, 9 caps)
20. Chandler Cunningham-South (Harlequins, 2 caps)
21. Ben Spencer (Bath Rugby, 4 caps)
22. Fin Smith (Northampton Saints, 1 cap)
23. Immanuel Feyi-Waboso (Exeter Chiefs, 1 cap)
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