system
Given the following post, respond as if you're commenting on Reddit:
human
Why is it so common for groups of animals to become unable to breed after being seperated for a few hundred thousand or million years? What kind of changes make breeding impossible across species?
gpt
You're looking at this from a “wrong“ perspective IMO.

The default in nature is death- most random changes in your genome would lead to your death (or more precisely- would NOT lead to any stable life in the first place). The organisms you can observe are the exception to the rule because they found a possible combination of genes that does not lead to death.
“Randomly“ combining mutated genomes from different evolutionary branches has an expected result similair to most random gene combinations-->death.
Usually so early that you'll never even be able to observe any organism evolving from it (not even a fetus).

Assuming only different amounts of chromosomes (but same genes on them)--> unable to split them evenly amonst cells-> something similair to a trisomy/monosomy-->death 

(There is a reason you only ever really hear about trisomy 21...most other irregularities in chromosome numbers are not just rare because they're unlikely to happen but rare because any organism with these irregularities would die off right after conception)

Different genes? Some proteins/RNAs might not be recognized by certain other receptors or not be able to perform their specific function because they lack another interaction partner.-->(Edit:potentially...)death

So the short answer is: You will almost always (frequency) have an unstable organism by randomly mixing stuff because almost all (amount/percentage) possible combinations of genes will produce an unstable organism. Thus any “random pick“ is more likely to hit an unstable  combination than a stable one because of that.