9 Natural Selection, Genetic Variation, and Human Diversity
209
study by Enard et al. found that after controlling for genomic features, a greater
fraction of amino acid substitutions may have been fixed by positive selection
(Enard et al. 2014). However, Enard et al. concluded background selection is still the
predominant type of selection affecting neutral diversity across the genome. Thus,
while negative selection has affected a larger proportion of the genome, positive
selection has had a stronger effect at the modest number of regions it has influenced
(Verrelli et al. 2002; Lohmueller et al. 2011a).
Because advantageous alleles provide information about specific human adaptations, positive selection has been widely studied. Both interspecific and intraspecific
adaptations are of interest for studying positive selection in humans. First, positive
selection specific to the human lineage can provide information about unique human
characteristics. These human-specific adaptations can be identified by looking
for alleles that have become fixed in Homo sapiens but are absent in the other
great apes (Tishkoff et al. 2001; Sabeti et al. 2002; Verrelli et al. 2002; Nielsen
et al. 2007). Adaptive alleles identified by such interspecific comparisons are
usually the products of completed selective sweeps, and therefore, the surrounding
linked neutral variation is in the process of recovering. Recent positive selection
detectable by intraspecific comparisons is more pertinent to the characterization of
current human genetic variation. Adaptation of specific human populations to their
respective environments and subsistence strategies is responsible for most of these
ongoing or recently completed selective sweeps. Most recent work to characterize
the action of selection in the human genome has focused on adaptations shaped by
recent positive selection, and we will therefore focus on this topic for the remainder
of the chapter.
9.3
Demography and Selection
Extant patterns of human genomic variation are jointly influenced by natural
selection and human demographic history. Thus, it is necessary to understand and
account for the effects of demographic history when making inferences about
natural selection. To this end, here, we briefly summarize aspects of human
demographic history that are relevant for interpreting signals of selection in humans.
In particular, as described below, demographic history influences the amount of
genetic variation available for selection to act upon and impacts the signatures
imparted on standing levels of genetic variation that often complicate inferences
of selection. A more detailed discussion of inference of human demography can be
found in Chap. 8 by Wall.
Anatomically modern humans arose in Africa over 200,000 years ago, and a
relatively small group of individuals began what is now recognized as the out-ofAfrica dispersal between 50,000–100,000 years ago (Goldstein and Chikhi 2002;
Cavalli-Sforza 2007). The out-of-Africa dispersal ultimately led to the peopling
of the Middle East, Europe, Asia, and the Americas. Notably, the recent African
origin of modern humans and subsequent out-of-Africa dispersal likely explain
a number of features of human genetic variation such as lower levels of genetic
209
study by Enard et al. found that after controlling for genomic features, a greater
fraction of amino acid substitutions may have been fixed by positive selection
(Enard et al. 2014). However, Enard et al. concluded background selection is still the
predominant type of selection affecting neutral diversity across the genome. Thus,
while negative selection has affected a larger proportion of the genome, positive
selection has had a stronger effect at the modest number of regions it has influenced
(Verrelli et al. 2002; Lohmueller et al. 2011a).
Because advantageous alleles provide information about specific human adaptations, positive selection has been widely studied. Both interspecific and intraspecific
adaptations are of interest for studying positive selection in humans. First, positive
selection specific to the human lineage can provide information about unique human
characteristics. These human-specific adaptations can be identified by looking
for alleles that have become fixed in Homo sapiens but are absent in the other
great apes (Tishkoff et al. 2001; Sabeti et al. 2002; Verrelli et al. 2002; Nielsen
et al. 2007). Adaptive alleles identified by such interspecific comparisons are
usually the products of completed selective sweeps, and therefore, the surrounding
linked neutral variation is in the process of recovering. Recent positive selection
detectable by intraspecific comparisons is more pertinent to the characterization of
current human genetic variation. Adaptation of specific human populations to their
respective environments and subsistence strategies is responsible for most of these
ongoing or recently completed selective sweeps. Most recent work to characterize
the action of selection in the human genome has focused on adaptations shaped by
recent positive selection, and we will therefore focus on this topic for the remainder
of the chapter.
9.3
Demography and Selection
Extant patterns of human genomic variation are jointly influenced by natural
selection and human demographic history. Thus, it is necessary to understand and
account for the effects of demographic history when making inferences about
natural selection. To this end, here, we briefly summarize aspects of human
demographic history that are relevant for interpreting signals of selection in humans.
In particular, as described below, demographic history influences the amount of
genetic variation available for selection to act upon and impacts the signatures
imparted on standing levels of genetic variation that often complicate inferences
of selection. A more detailed discussion of inference of human demography can be
found in Chap. 8 by Wall.
Anatomically modern humans arose in Africa over 200,000 years ago, and a
relatively small group of individuals began what is now recognized as the out-ofAfrica dispersal between 50,000–100,000 years ago (Goldstein and Chikhi 2002;
Cavalli-Sforza 2007). The out-of-Africa dispersal ultimately led to the peopling
of the Middle East, Europe, Asia, and the Americas. Notably, the recent African
origin of modern humans and subsequent out-of-Africa dispersal likely explain
a number of features of human genetic variation such as lower levels of genetic