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Disease consequences of human adaptation ☆

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ABSTRACT

Adaptive evolution has provided us with a unique set of characteristics that define us as humans, including morphological, physiological and cellular changes. Yet, natural selection provides no assurances that adaptation is without human health consequences; advantageous mutations will increase in frequency so long as there is a net gain in fitness. As such, the current incidence of human disease can depend on previous adaptations. Here, I review genome-wide and gene-specific studies in which adaptive evolution has played a role in shaping human genetic disease. In addition to the disease consequences of adaptive phenotypes, such as bipedal locomotion and resistance to certain pathogens, I review evidence that adaptive mutations have influenced the frequency of linked disease alleles through genetic hitchhiking. Taken together, the links between human adaptation and disease highlight the importance of their combined influence on functional variation within the human genome and offer opportunities to discover and characterize such variation.

No MeSH data available.


Interference between positive and negative selection. Positive selection increases the frequency of advantageous mutations (red) and any linked neutral alleles (black). Negative selection eliminates deleterious mutations (blue) and any linked neutral alleles. Linkage can cause interference between positive and negative selection. If positive selection is stronger than negative selection, positive selection can fix a linked deleterious mutation, thereby interfering with negative selection. In the presence of recombination, a deleterious mutation can also increase in frequency due to hitchhiking but is not necessarily fixed.
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f0010: Interference between positive and negative selection. Positive selection increases the frequency of advantageous mutations (red) and any linked neutral alleles (black). Negative selection eliminates deleterious mutations (blue) and any linked neutral alleles. Linkage can cause interference between positive and negative selection. If positive selection is stronger than negative selection, positive selection can fix a linked deleterious mutation, thereby interfering with negative selection. In the presence of recombination, a deleterious mutation can also increase in frequency due to hitchhiking but is not necessarily fixed.

Mentions: As populations evolve, natural selection strives to increase the frequency of advantageous mutations and decrease the frequency of deleterious mutations (Fig. 2). Because of linkage, there are numerous opportunities for interferences between advantageous and deleterious mutations (Hill and Robertson, 1966). Thus, a strongly advantageous mutation has the potential to increase the frequency of linked deleterious mutations (Fig. 2). While the frequency of interference between advantageous and deleterious mutations is not known, recent work suggests that interference is common enough to have influenced disease alleles in humans.


Disease consequences of human adaptation ☆
Interference between positive and negative selection. Positive selection increases the frequency of advantageous mutations (red) and any linked neutral alleles (black). Negative selection eliminates deleterious mutations (blue) and any linked neutral alleles. Linkage can cause interference between positive and negative selection. If positive selection is stronger than negative selection, positive selection can fix a linked deleterious mutation, thereby interfering with negative selection. In the presence of recombination, a deleterious mutation can also increase in frequency due to hitchhiking but is not necessarily fixed.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121272&req=5

f0010: Interference between positive and negative selection. Positive selection increases the frequency of advantageous mutations (red) and any linked neutral alleles (black). Negative selection eliminates deleterious mutations (blue) and any linked neutral alleles. Linkage can cause interference between positive and negative selection. If positive selection is stronger than negative selection, positive selection can fix a linked deleterious mutation, thereby interfering with negative selection. In the presence of recombination, a deleterious mutation can also increase in frequency due to hitchhiking but is not necessarily fixed.
Mentions: As populations evolve, natural selection strives to increase the frequency of advantageous mutations and decrease the frequency of deleterious mutations (Fig. 2). Because of linkage, there are numerous opportunities for interferences between advantageous and deleterious mutations (Hill and Robertson, 1966). Thus, a strongly advantageous mutation has the potential to increase the frequency of linked deleterious mutations (Fig. 2). While the frequency of interference between advantageous and deleterious mutations is not known, recent work suggests that interference is common enough to have influenced disease alleles in humans.

View Article: PubMed Central - PubMed

ABSTRACT

Adaptive evolution has provided us with a unique set of characteristics that define us as humans, including morphological, physiological and cellular changes. Yet, natural selection provides no assurances that adaptation is without human health consequences; advantageous mutations will increase in frequency so long as there is a net gain in fitness. As such, the current incidence of human disease can depend on previous adaptations. Here, I review genome-wide and gene-specific studies in which adaptive evolution has played a role in shaping human genetic disease. In addition to the disease consequences of adaptive phenotypes, such as bipedal locomotion and resistance to certain pathogens, I review evidence that adaptive mutations have influenced the frequency of linked disease alleles through genetic hitchhiking. Taken together, the links between human adaptation and disease highlight the importance of their combined influence on functional variation within the human genome and offer opportunities to discover and characterize such variation.

No MeSH data available.