590 CHAPTER 22diseases, acquired from domesticated animals; and sedentary life in villages
created environmental conditions such as standing water, which increased the
abundance of mosquitoes and of mosquito-borne diseases such as malaria. The
Industrial Revolution, and especially the modern technological life that it made
possible, has certainly had some positive effects on health (such as modern sci-
ence and medicine), but it has given rise to “diseases of civilization,” including
cardiovascular disease, obesity, and type II diabetes. The best recipe for escaping
these diseases is plenty of exercise, eating in moderation, and avoiding nutrient-
poor, calorie-rich processed foods, with their starch and refined sugar.
We also noted in Chapter 21 that a diverse microbiome is essential for nor-
mal development of the immune system, and that urban environments and an
obsession with “germs” reduce exposure to the diverse bacteria and other antigens
that humans have experienced throughout evolutionary history [100]. As a result,
autoimmune diseases such as inflammatory bowel disease, asthma, and severe
allergies have become more prevalent. Similarly, disrupting the gut microbiome by
antibiotics, especially in young children when the immune system is developing,
greatly increases the risk of developing autoimmune diseases later [12]. Members
of the human microbiome have some direct beneficial effects as well. Some directly
benefit the human host; for example, the gut bacterium Bacteroides fragilis triggers
gut cells to produce lymphoid tissue that prevents bacteria from penetrating the
gut wall. Some microbial species suppress harmful bacteria, such as Clostridium
difficile, which often takes over the intestine after excessive antibiotic treatment
(see Figure 21.22).GEnETiC diSEASES Although some inherited diseases have epigenetic causes,
the great majority are caused by mutations in DNA sequences and chromosomal
aberrations [105]. Most base pair mutations in humans enter the population
through sperm, and the average mutation rate (about 10–8 per base pair) increases
considerably during a man’s life. Most nonsynonymous mutations slightly reduce
fitness [41]. Many inherited maladies, such as psychiatric illnesses, have a poly-
genic basis [50], but specific genes and mutations have been identified for many
inherited defects. Many of them are rare mutations that represent the opposition
of mutation and purifying selection, but some—most famously those that enhance
resistance to malaria—are alleles that have—or had, in the past—countervail-
ing advantageous effects (see Chapter 5). In traditional societies, some antago-
nistically pleiotropic mutations that increased fitness at an early age may have
expressed injurious effects late in life, at ages that few people attained in the past.
Today, when the average human life span is much greater, the deleterious effects
of these mutations are more commonly encountered. Possible examples include
the BRCA1 and BRCA2 mutations that cause breast cancer and the APOE4 muta-
tion that may be advantageous for children’s cognitive development but is associ-
ated with a greater risk of developing Alzheimer’s disease later in life [87, 108].CAnCER Somatic mutations—those that occur in cells that do not give rise to
gametes—are the primary causes of cancers [72, 105]. Cancer is an evolutionary
process: selection among genetically different cell lineages (clones) favors rap-
idly increasing lineages. Somatic mutations occur at a fairly high rate; by middle
age, skin cells exposed to sun carry thousands of mutations. Cancers result only
from mutations in certain “driver” genes that increase cell division, and several
such mutations are required. As a tumor grows, mutations continue and mark
descendant cells, so phylogenetic analysis can trace the history of a cancer, just as
it can trace gene trees in populations and species (see Chapter 16). Such studies
have shown that driver mutations may initiate cancers early in life, long before22_EVOL4E_CH22.indd 590 3/22/17 1:49 PM