We know that the diseases that plague humans have changed at least in recent history.
Many of our chronic diseases are assumed to be the result of a "mismatch" between our present environment and the environment that supposedly persisted for most of our evolution when we were "hunter/gatherers" living in small groups.
http://en.wikipedia.org/wiki/Mismatch_theory
There are a wealth of hypotheses, including mitigating factors such as past favorable selection for the trait, time lags and genetic drift.
Initially most mismatches were attributed to us as evolved hunter-gatherers now captives of modern city life and also the time it takes for changes, especially since modern life offers fixes for some conditions and so shields predisposing genes from selection.
Lately however scientists have questioned these assumptions.
For example, The conservative genes found in Neanderthals that predispose to obesity and diabetes. why are they there?
https://sitn.hms.harvard.edu/flash/2014/the-not-so-secret-life-of-our-inner-neanderthal/
Theory rests on the assumption that humans were expanding and migrating at a time when climate was changing and not for the better with regard to food supplies.
There is good evidence for this.
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Just at the start of expansion, Africa became more open grassland, with more antelopes and other herbivores. The idea is that humans began eating tougher material and adding more meat to their diet. Our bodies evolved to be in harmony with this life style. But with agriculture came a narrow range of selected grains and animals. Industrialization added easier access to food and processed food. Both of these huge environmental changes lead to large mismatches between human biology and their present environment.
But there are also problems with these hypothesis, because there are huge gaps between more stable time and unstable times.
Why were these genes not subject to negative selection at this time.
Again, some of thee theories involve environmental changes occurring well after Neanderthals and humans interbred, and so it is difficult to know what kept those genes at a selective advantage until the theories indicate a selective advantage for them. Again genetic drift? but that's a lot of drift and all going in the right direction.
What about the idea that more recent big changes, the first coming with agriculture and the other with industrialization, have caused mismatches between our present environment and previously positively selected genes.
These ideas seem logical, cities are very different places than forest edges, etc.
But there are problems with this idea also.
1. Natural selection, and since agriculture has been around, has selected for "matching" with the environment.
Example http://evolution.berkeley.edu/evolibrary/news/101001_altitude
Note the adaptation here is different than expected from looking at how in general individuals adapt to high altitudes if they normally live at low altitudes
Some experts argue that indices of "fitness" such as height, which decreased with large scale farms returned to averages before farm expansion in less than 4000 years.
2. Also the evidence is scanty with regard to exactly how primitive-hunter gatherers lived.
Evidence from present day hunter gatherers seems to indicate, for example, a great variety in diet.
New evidence seems to indicate that we may have been adapted for what we had to eat during times of stress, but that doesn't mean our diets match our adaptations perfectly. There is evidence in the grit found on teeth that although the size and width of teeth appear to be adapted to chewing tough fibers, the grit on these teeth indicate this individual at the time of its demise preferred fruit.
There are disagreements about almost all aspects of paleo life. For example, it was thought that the ability to cook allowed selection for less processing and so smaller teeth, but smaller teeth are now believed to predate the invention of cooking and may have been due to mechanical processing of food by humans before consumption (teeth did not have to tear the meat from the bone).
Even what we thought Neanderthals ate is debated.
The short story is it does look like there are basic differences between almost all hunter gatherer groups and our modern diets.
But returning to old diets will be hard, we have completely modified through domestication the amounts of fats versus proteins found in animals and the amount of carbohydrates and proteins found in vegetables.
"Mega farming" is new . https://en.wikipedia.org/wiki/History_of_agriculture
Farming as we know it today begins after the ice age about 12,000 years ago or as some estimate about 300 human generations ago. A more benevolent climate let to settlements which led to "pastoral" farming. First farmers are not yet subject to the plagues, etc of later farmers and they probably supplemented farming with hunting –gathering.
There is some evidence that the growth of farming is associated the first population explosion. It is estimated that during hunting and gathering men can collect from 3000-6000 calories a day and women about 2000. It is estimated that early farmers could acquire 12,800 calories a day.
Animals and plants undergo domestication, providing more food, but also less diversity in food items.
Settlements can get larger and so subject to contaminated food, famine, pests and parasites. The domestic mouse Mus musculus evolved with the event of agriculture in Southwest Asia. Eventually there is evidence for large scale plagues and famines.
This has lead to food that is starchier, and contains less protein and vitamins.
Pick out from the first half and last half of the chapter, three facts and their implications, you feel worthy enough to be memorized.
Current focus in researches on mismatches. For your information only.
Focus has turned to the human micro-fauna and what is a "normal" micro-fauna.
Emphasis continues on genes inherited from Neanderthals and now Denisovans. See the references below if interested.
https://www.nature.com/articles/d41586-021-00388-2
https://www.nature.com/articles/s41559-020-1243-1
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254175
