Adaptive Landscape of Protein Variation in Human Exomes

Molecular Biology and Evolution
Ravi PatelSudhir Kumar

Abstract

The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles experienced a reversal of fortune in the human lineage. We explored nonadaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Many nonadaptive hypotheses were tested, but failed to explain the data, which suggests that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This suggestion is supported by the fact that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and hund...Continue Reading

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Citations

Dec 20, 2018·Molecular Ecology Resources·Benjamin C HallerPeter L Ralph
Feb 23, 2020·Annual Review of Biophysics·Paul CampitelliS Banu Ozkan
Jun 27, 2019·BMC Evolutionary Biology·Ravi Patel, Sudhir Kumar
Mar 7, 2021·Journal of Personalized Medicine·Laura B ScheinfeldtNeda Gharani
Apr 24, 2021·Molecular Biology and Evolution·Koichiro TamuraSudhir Kumar

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Software Mentioned

PANTHER
SLiM2
pyvolve
R script
Moments
R Team
SliM2 script

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