human biology - Has a beneficial mutation ever been documented?

I am trying to find a case/study where scientists documented a mutation in an animal or human that was to the benefit of the host.

The closest thing I have been able to find is sickle cell anemia (SCA) helping to fight malaria. However, the life expectancy for people with SCA is 40 – 60 years, and in 1973 it was only 14 years (source). I am looking for another case, preferably one that is not life-threatening.

Are there any other cases where a beneficial mutation — one where the good outweighs the bad — was documented?

By beneficial I simply mean that it helps or protects the host in some way, while not causing substantial harm. As in my example of SCA it can benefit the host if the host lives in an area with malaria. However, it is also life threatening and reduces the life expectancy of the host.

If — for example — SCA would only cause pain and not be life-threatening, then it would (in my opinion) be a beneficial mutation. While not purely beneficial, it would still increase the life expectancy of people living in an area with a high occurrence of malaria.

Answer

Lactase persistence

This is a somewhat unusual example but has been well studied, and would seem to satisfy the criteria of the question. Let me start by quoting the Wikipedia entry for those unfamiliar with the phenomenon:

Lactase persistence is the continued activity of the enzyme lactase in adulthood. Since lactase’s only function is the digestion of lactose in milk, in most mammal species, the activity of the enzyme is dramatically reduced after weaning.[1] In some human populations, though, lactase persistence has recently evolved[2] as an adaptation to the consumption of nonhuman milk and dairy products beyond infancy.

Studies on the geographical distribution of lactase persistence (e.g. AJHG (2014) vol 94, pp. 496–510) show that lactase persistence is associated with cultures which practice pastoralism (specifically herding bovines), supporting the hypothesis that the trait evolved because of the benefit it conveyed to such populations in allowing them to use bovine (or caprine or ovine) milk to survive in adulthood.

There is no doubt that lactase persistence is a heritable — i.e. genetic — trait, as can be seen from consulting the OMIH (Online Mendelian Inheritance in Man) entry. This has extensive documentation, including description of the base changes associated with the trait:

Enattah et al. (2002) found a complete association between biochemically verified lactase nonpersistence in Finnish families and a C/T(-13910) polymorphism of the MCM6 gene (601806.0001) roughly 14 kb upstream from the lactase gene locus (LCT; 603202), located on 2q21. It was the C allele that associated with hypolactasia.

The molecular mechanism of lactase nonpersistence (the putative original human condition) — affected by mutation at this position — is still not completely clear. Recent work suggests:

Epigenetically controlled regulatory elements accounted for the differences in lactase mRNA levels among individuals, intestinal cell types and species.

Finally, I refer to the evidence for the Wikipedia statement that “lactase persistence has recently evolved[2]”. This is a paper by Bersaglieri et al. in The American Journal of Human Genetics (Am. J. Hum. Genet. 74:1111–1120, 2004). I am not a population geneticist, so I shall reproduce the relevant section of their summary unedited:

In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. 2002) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for 11 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional F_ST measure and a novel test based on p_excess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome.