Intriguing Balancing Selection on the Intron 5 Region of LMBR1 in Human Population

Background: The intron 5 of gene LMBR1 is the cis-acting regulatory module for the sonic hedgehog (SHH) gene. Mutation in this non-coding region is associated with preaxial polydactyly, and may play crucial roles in the evolution of limb and skeletal system. Methodology/Principal Findings: We sequenced a region of the LMBR1 gene intron 5 in East Asian human population, and found a significant deviation of Tajima’s D statistics from neutrality taking human population growth into account. Data from HapMap also demonstrated extended linkage disequilibrium in the region in East Asian and European population, and significantly low degree of genetic differentiation among human populations. Conclusion/Significance: We proposed that the intron 5 of LMBR1 was presumably subject to balancing selection during the evolution of modern human

Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation

Genome-wide scans for positive selection in humans provide a promising approach to establish links between genetic variants and adaptive phenotypes. From this approach, lists of hundreds of candidate genomic regions for positive selection have been assembled. These candidate regions are expected to contain variants that contribute to adaptive phenotypes, but few of these regions have been associated with phenotypic effects. Here we present evidence that a derived nonsynonymous substitution (370A) in EDAR, a gene involved in ectodermal development, was driven to high frequency in East Asia by positive selection prior to 10,000 years ago. With an in vitro transfection assay, we demonstrate that 370A enhances NF-κB activity. Our results suggest that 370A is a positively selected functional genetic variant that underlies an adaptive human phenotype

Patterns of Polymorphism and Demographic History in Natural Populations of Arabidopsis lyrata

Many of the processes affecting genetic diversity act on local populations. However, studies of plant nucleotide diversity have largely ignored local sampling, making it difficult to infer the demographic history of populations and to assess the importance of local adaptation. Arabidopsis lyrata, a self-incompatible, perennial species with a circumpolar distribution, is an excellent model system in which to study the roles of demographic history and local adaptation in patterning genetic variation.We studied nucleotide diversity in six natural populations of Arabidopsis lyrata, using 77 loci sampled from 140 chromosomes. The six populations were highly differentiated, with a median FST of 0.52, and structure analysis revealed no evidence of admixed individuals. Average within-population diversity varied among populations, with the highest diversity found in a German population; this population harbors 3-fold higher levels of silent diversity than worldwide samples of A. thaliana. All A. lyrata populations also yielded positive values of Tajima's D. We estimated a demographic model for these populations, finding evidence of population divergence over the past 19,000 to 47,000 years involving non-equilibrium demographic events that reduced the effective size of most populations. Finally, we used the inferred demographic model to perform an initial test for local adaptation and identified several genes, including the flowering time gene FCA and a disease resistance locus, as candidates for local adaptation events.Our results underscore the importance of population-specific, non-equilibrium demographic processes in patterning diversity within A. lyrata. Moreover, our extensive dataset provides an important resource for future molecular population genetic studies of local adaptation in A. lyrata