It normally takes 2-4 weeks to get up to speed on the letters; learning the punctuation can take another week or two since it typically needs the fn layer. Eventually you get a pretty dramatic increase in comfort, but there’s definitely a learning curve. (Source: I have sold hundreds of DIY keyboard kits with a similar column stagger and heavy use of the fn key.) If you use programs that don’t support rebinding the keys (for instance, hard-coded reliance on f1-12) then it will likely take longer and end up being a fair bit more awkward even once you’ve learned it.

Learning to touch type (Dvorak) comfortably took some time, but after that, switching to a split keyboard (first Microsoft Natural Ergonomic then Kinesis Advantage Pro) wasn’t a big challenge at all.

I have a gold touch split keyboard - which I’m using daily at work - and I’m hoping to replace with ultimate hacking keyboard in the near future, but I’ve been using Microsoft Ergonomic keyboards for years and I found them just more comfortable - the challenge is learning the new keyboard layout, but their have been threads here on lobste.rs about different layouts - I also use zty.pe to practice touch typing when I want to get back up to speed. Not sure this really answers your question, but my experience switching to both the gold touch and ergonomic keyboards was that the comfort of typing quickly built my touch typing speeds back up (I touch type at about 100 WPM but only with a 60 WPM minute accuracy :~/)