Population-genetic nature of copy number variations in the human genome

Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000–4000 CNVs (4–6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV–SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV–SNP linkage disequilibrium (LD) for 500–900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP–SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs

Supplementary Information for: Genetic adaptations in the population history of Arabidopsis thaliana

<p>A population encounters a variety of environmental stresses, so the full source of its resilience can only be captured by collecting all the signatures of adaptation to the selection of the local environment in its population history. Based on the multi-omic data of <em>Arabidopsis thaliana</em>, we constructed a database of phenotypic (p-adaptations) and gene expression (e-adaptations) adaptations in the population. Through the enrichment analysis of the identified adaptations, we inferred a likely scenario of adaptation that is consistent with the biological evidence from experimental work. We analyzed the dynamics of the allele frequencies at the 23,880 QTLs of 174 traits and 8,618 eQTLs of 1,829 genes with respect to the total SNPs in the genomes, and identified 650 p-adaptations and 3,925 e-adaptations (FDR=0.05). The population underwent large scale p-adaptations and e-adaptations along four lineages. Extremely cold winters and short summers prolonged seed dormancy, and expanded the root system architecture. Low temperatures prolonged the growing season and low light intensity required the increased chloroplast activity. The subtropical and humid environment enhanced phytohormone signaling pathways in response to the biotic and abiotic stresses. Exposure to heavy metals selected alleles for lower heavy metal uptake from soil, lower growth rate, lower resistance to bacteria, and higher expression of photosynthetic genes were selected. The p-adaptations are directly interpretable, while the co-adapted gene expressions reflect the physiological requirements for the adaptation. The integration of this information characterizes when and where the population has experienced environmental stress and how the population responded at the molecular level.</p&gt

Data from: Population structure and persistence of Pacific herring following the Great Tohoku earthquake

We evaluated the effect of the Great Tohoku earthquake, which occurred on March 11, 2011 in Japan, on the genetic diversity and population structure of Pacific herring (Clupea pallasii). Pacific herring (n = 4466) were collected between 2003 and 2014 through more than 20 sampling events during spawning periods at nine spawning sites throughout the Pacific herring distribution range in Japan. We measured them and genotyped 3784 fish at five microsatellite loci. Following the tsunami, the sea-spawning population at the center of the affected area was almost extirpated and was replaced by a genetically distinct lagoon-spawning population from an adjacent brackish lake. However, the pattern of gene flow was stable for populations, with unique admixture proportions in local populations despite the high gene flow (FST = 0.0184). Our results indicate that Pacific herring in Japan spawn in a range of salinities and exchange genes between local populations regardless of the spawning ecotypes. We hypothesize that the combination of constant gene flow between local populations from straying of spawners and spawning fidelity creates weak but significantly differentiated stable population structure. This process can allow restoration of the genetic characteristics of damaged populations over many generations and can thereby promote the long-term viability of marine fishes that have high gene flow

Japan_herring_genepop

Microsatellite genotypes for 20 samples (n=3,784) collected from nine major spawning sites in Japan during the spawnng season before and after the Great Tohoku earthquak