Speaking to the BBC’s Good Morning Scotland programme, the veteran pollster said the repercussions of Brexit were likely to shape the discussion over the country’s future.
He said the issue “certainly looks as though it's going to dominate” the election campaign.
"The proposition the SNP are putting forward... is that if Scotland were to come independent country it would be applying to go back inside the European Union,” explained Sir John.
“Of course the rest of the UK is now outside, unlike in 2014, so that raises questions about what would happen to the border between Gretna and Berwick - it will become a border of the European Union single market.
“What are the implications of that for trade flows between Scotland and the United Kingdom? Would Scotland be able to re-orientate its trade much more to the larger single market of the European Union?”
He added: “The choice we now face is clearly very, very different from what it was seven years ago.”
The University of Strathclyde academic also said that while the independence debate in recent months had been focused on the timing of a second referendum, that could be set to change.
“The argument for those, particularly on the unionist side, is in the midst of a pandemic, or indeed shortly after a pandemic when we're still dealing with the economic consequences, is not an appropriate time to hold a referendum.
“Whereas of course those inside the SNP are arguing it certainly should be within the first half of the next parliamentary term.”
“We might hope that our parties would talk about...the argument of principle: i.e. would Scotland be better off as independent country or not? What are the arguments for and against Scotland being within the union versus being independent?”
He continued: “It'll be interesting to see whether or not the substantive argument about the merits of independence being in the union comes to the fore, rather than a lot of discussion about the tactics or the timing of a referendum.”