However, in the last half century, there has been considerable debate as to whether evolutionary changes at the molecular level are largely driven by natural selection or random genetic drift.
Quantifying adaptive evolution in the human genome gives insights into our own evolutionary history and helps to resolve this neutralist-selectionist debate.
These genomic methods can also be applied to search for adaptive evolution in non-coding DNA, where putatively neutral sites are hard to identify (Ponting and Lunter 2006).
Many different studies have attempted to quantify the amount of adaptive evolution in the human genome, the vast majority using the comparative approaches outlined above.
This comparatively early study used relatively few loci (fewer than 200) for their estimate, and the polymorphism and divergence data used was obtained from different genes, both of which may have led to an overestimate of α.
However, the MK test used in this study was sufficiently weak that the authors state that this value of α is not statistically significantly different from 0%.
Therefore, the fact that many estimates are at (or very near to) 0% does not rule out the occurrence of any adaptive evolution in the human genome, but simply shows that positive selection is not frequent enough to be detected by the tests.
In fact, the most recent study mentioned states that confounding variables, such as demographic changes, mean that the true value of α may be as high as 40% (Eyre-Walker and Keightley 2009).
Even if low estimates of α are accurate, a small proportion of substitutions evolving adaptively can still equate to a considerable amount of coding DNA.
Generally, there does appear to be a positive correlation between (effective) population size of the species, and amount of adaptive evolution occurring in the coding DNA regions.
This may be because random genetic drift becomes less powerful at altering allele frequencies, compared to natural selection, as population size increases.
Where there is evidence of adaptive evolution (which implies functionality) in non-coding DNA, these regions are generally thought to be involved in the regulation of protein coding sequences.
Several recent studies have compared the amounts of adaptive evolution occurring between different populations within the human species.
This is because there has been a large acceleration in the amount of positive selection in the human lineage over the last 40,000 years, in terms of the number of genes that have undergone adaptive evolution (Hawks et al. 2007).
This agrees with simple theoretical predictions, because the human population size has expanded dramatically in the last 40,000 years, and with more people, there should be more adaptive substitutions.
A considerable number of studies have used genomic methods to identify specific human genes that show evidence of adaptive evolution.
For example, schizophrenia has been linked with increased creativity (Crespi et al. 2007), perhaps a useful trait for obtaining food or attracting mates in Palaeolithic times.
417 genes involved in the immune system showed strong evidence of adaptive evolution in the study of Nielsen et al. (2005a).
This is probably because the immune genes may become involved in an evolutionary arms race with bacteria and viruses (Daugherty and Malik 2012; Van der Lee et al. 2017).
This is likely to be because those humans that left Africa approximately 50,000 years ago, entered less sunny climates, and so were under new selection pressures to obtain enough Vitamin D from the weakened sunlight.
While there are many different modifications applied to individual tests to overcome the associated problems, two types of confounding variables are particularly important in hindering the accurate detection of adaptive evolution: demographic changes and biased gene conversion.
The human lineage has undergone both rapid population size contractions and expansions over its evolutionary history, and these events will change many of the signatures thought to be characteristic of adaptive evolution (Nielsen et al. 2007).
A phenomenon which could severely alter the way we look for signatures of adaptive evolution is biased gene conversion (BGC) (Galtier and Duret 2007).
However, it is unlikely that HARs are generally maladaptive, because DNA repair mechanisms themselves would be subject to strong selection if they propagated deleterious mutations.