74 What is Autism?
What is the Mutation Rate in the Whole Human Genome?
For selfish reasons, we as humans are fundamentally interested in the mutation
rate in our own species, and a number of questions are unresolved or still only
partially answered. A central parameter is the average number of new genetic
variants each of us has that our parents did not possess. How many of these
mutations came from our father and our mother, how much does the mutation
rate change with parental age, and is there significant variation in the mutation
rate in the population as a consequence of other environmental or genetic fac-
tors? A more difficult question to answer concerns the frequency of mildly
deleterious mutations and the distribution of their fitness effects. Along with
the nature of selection on fitness in human populations, these parameters hold
the key to understanding how a high genomic rate of deleterious mutation can
be tolerated without causing an implausibly high rate of genetic death. Finally,
if natural selection has been relaxed in current populations, what are the plau-
sible consequences of mutation accumulation in our species?
Mean estimates for mutation rates on a nucleotide site basis have been cal-
culated at 1.8×10−8 and 1.3×10−8 per generation by Kondrashov [68], and Lynch
and Conery [(69], respectively. These estimates align with other calculations
based on the divergence of humans and chimpanzees as well as direct genome
sequencing of parent–offspring trios. Deletions appear to occur approximately
three times more often than insertions, whereas small insertion–deletions are
relatively uncommon, occurring only in approximately 4% of mutations and
only about 10% as often as single nucleotide events [68]. Thus, small inser-
tion–deletions seem to have much lower importance in humans than in inver-
tebrates (e.g., Caenorhabditis elegans, Drosophila) or flowering plants (e.g.,
Arabidopsis thaliana) [70].Does Brain Size Matter?
The brains of humans and other nonhuman primates contain the same struc-
tures as the brains of other mammals, but are generally larger in proportion to
body size. The most widely accepted method for comparing brain sizes across
species is the encephalization quotient (EQ), which takes into account the non-
linearity of the brain‐to‐body relationship. Humans have an average EQ in the
7–8 range, while most other primates have an EQ in the 2–3 range. Dolphins
have values higher than those of primates other than humans, but nearly all
other mammals have EQ values that are substantially lower (Table 2.2) [71].
Most of the enlargement of the primate brain comes from a massive expan-
sion of the cerebral cortex, especially the prefrontal cortex and the parts of the