Its more a matter of tiredness and stress than mutation. The yeast has certain internal resources, that are best built up in the presence of oxygen, abundant nutrients and lack of poison (which both alcohol and C02 are to a yeast). So in your wort, as soon as the yeast have used up all the available oxygen, they are soldiering on, on a combination of what they already have stored up and what they can try to synthesise out of the wort.. which is much harder for them without oxygen.
The bigger the beer and the less yeast you pitch - the harder you are asking the yeast to work with the resources they have on hand. A smaller number of cells will have to multiply up to the required level and still have the internal resources to chomp through the amount of sugar you threw at them.. and the bigger the beer, the more hostile an environment you are asking them to do it in.
This makes em work really hard - which doesn't necessarily lead to them producing the best flavours and might lead to them actually conking out before they have finished the job - giving you an underattenuated beer and perhaps leftover diacetyl and acetylaldhyde etc.
Most pitching rates recommendations are predicated on the notion that you will need a certain number of cells per millileter, per degree plato. The number is calculated to both make sure that the yeast are capable of fully fermenting the wort and to give an optimum number of generations growth to reach the cell numbers required for the wort. The more generations of growth... the more yeast "character" there will be because yeast pump out a lot of their flavour products when they are in their reproductive phase. So for a lager you might only want 3 or so generations and a clean flavour profile, but in a nice estery ale... you might look for 5-6 generations. So you need to pitch more into the lager in the first place.
But its a range not a hard and fast rule, and care with temperature control can influence the character of the beer in the opposite direction to pitching rate (or enhance it).
In general - you are probably better off over pitching than underpitching. But there are problems with both. A nice pitching rate calculator such as teh Wyeast one or the one at www.mrmalty.com will get you into a nice safe zone... and then its a matter of experience and tweaking to fine tune your results.
Yeast handling is a combination of art, mysticism and animal husbandry... When you master it, let me know and tell me how to do it will you??
Thirsty
