Diversity of Lactase Persistence Alleles in Ethiopia: Signature of a Soft Selective Sweep

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.

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The Effect of Deleterious Alleles on Adaptation in Asexual Populations

Genetics ◽

10.1093/genetics/162.1.395 ◽

2002 ◽

Vol 162 (1) ◽

pp. 395-411 ◽

Cited By ~ 2

Author(s):

Toby Johnson ◽

Nick H Barton

Keyword(s):

Selective Sweep ◽

Deleterious Mutation ◽

Short Interval ◽

Selective Advantage ◽

Asexual Population ◽

Restrictive Assumption ◽

Deleterious Alleles ◽

Fixation Probabilities ◽

Asexual Populations ◽

Beneficial Allele

Abstract We calculate the fixation probability of a beneficial allele that arises as the result of a unique mutation in an asexual population that is subject to recurrent deleterious mutation at rate U. Our analysis is an extension of previous works, which make a biologically restrictive assumption that selection against deleterious alleles is stronger than that on the beneficial allele of interest. We show that when selection against deleterious alleles is weak, beneficial alleles that confer a selective advantage that is small relative to U have greatly reduced probabilities of fixation. We discuss the consequences of this effect for the distribution of effects of alleles fixed during adaptation. We show that a selective sweep will increase the fixation probabilities of other beneficial mutations arising during some short interval afterward. We use the calculated fixation probabilities to estimate the expected rate of fitness improvement in an asexual population when beneficial alleles arise continually at some low rate proportional to U. We estimate the rate of mutation that is optimal in the sense that it maximizes this rate of fitness improvement. Again, this analysis relaxes the assumption made previously that selection against deleterious alleles is stronger than on beneficial alleles.

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Nucleotide Variation at theCHALCONE ISOMERASELocus inArabidopsis thaliana

Genetics ◽

10.1093/genetics/155.2.863 ◽

2000 ◽

Vol 155 (2) ◽

pp. 863-872 ◽

Cited By ~ 14

Author(s):

Helmi Kuittinen ◽

Montserrat Aguadé

Keyword(s):

Nucleotide Diversity ◽

Direct Relationship ◽

Selective Sweep ◽

Balancing Selection ◽

Neutral Theory ◽

Low Frequency ◽

The Other ◽

Nucleotide Variation ◽

Rapid Population Growth ◽

History Of

AbstractAn ~1.9-kb region encompassing the CHI gene, which encodes chalcone isomerase, was sequenced in 24 worldwide ecotypes of Arabidopsis thaliana (L.) Heynh. and in 1 ecotype of A. lyrata ssp. petraea. There was no evidence for dimorphism at the CHI region. A minimum of three recombination events was inferred in the history of the sampled ecotypes of the highly selfing A. thaliana. The estimated nucleotide diversity (θTOTAL = 0.004, θSIL = 0.005) was on the lower part of the range of the corresponding estimates for other gene regions. The skewness of the frequency spectrum toward an excess of low-frequency polymorphisms, together with the bell-shaped distribution of pairwise nucleotide differences at CHI, suggests that A. thaliana has recently experienced a rapid population growth. Although this pattern could also be explained by a recent selective sweep at the studied region, results from the other studied loci and from an AFLP survey seem to support the expansion hypothesis. Comparison of silent polymorphism and divergence at the CHI region and at the Adh1 and ChiA revealed in some cases a significant deviation of the direct relationship predicted by the neutral theory, which would be compatible with balancing selection acting at the latter regions.

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Reduced Variation in Drosophila simulans Mitochondrial DNA

Genetics ◽

10.1093/genetics/144.4.1519 ◽

1996 ◽

Vol 144 (4) ◽

pp. 1519-1528

Author(s):

J William O Ballad ◽

Joy Hatzidakis ◽

Timothy L Karr ◽

Martin Kreitman

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Evolutionary Dynamics ◽

Selective Sweep ◽

Mitochondrial Gene ◽

Drosophila Simulans ◽

Dramatic Reduction ◽

Nucleotide Variability ◽

Pooled Samples ◽

Mitochondrial Gene Mutation

We investigated the evolutionary dynamics of infection of a Drosophila simulans population by a maternally inherited insect bacterial parasite, Wolbachia, by analyzing nucleotide variability in three regions of the mitochondrial genome in four infected and 35 uninfected lines. Mitochondrial variability is significantly reduced compared to a noncoding region of a nuclear-encoded gene in both uninfected and pooled samples of flies, indicating a sweep of genetic variation. The selective sweep of mitochondrial DNA may have been generated by the fixation of an advantageous mitochondrial gene mutation in the mitochondrial genome. Alternatively, the dramatic reduction in mitochondrial diversity may be related to Wolbachia.

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