Fig 1.
Signatures of ancient haplotype blocks with population-specific positive selection.
(A) Some important loci adapted to ancient African environment arose (red triangle) and formed haplotype blocks. The haplotype blocks spread during human migration, and some mutations may have occurred for adaptation to each environment (blue and green triangles). This change is a signature of an ancient haplotype block with population-specific positive selection. (B) A proposed network model to represent the positive selection signature. Each node represents the population in a region. Throughout this paper, red, blue, and green nodes represent populations in Africa, Europe, and Asia, respectively. Arrows represent migration routes. Edges represent relationships between populations. In this work, relationships were evaluated using t-statistic scores that represent degrees of difference between populations. Asterisks represent mutations.
Fig 2.
HapMap SNPs from three populations.
The relationships between the numbers of SNPs in 22 autosomal chromosomes from three populations, YRI, CEU, and ASN, in the HapMap database are shown. A total of 3,619,226 SNPs were found in all three populations. Among them, 879,657 SNPs were selected under the condition that all of the SNPs could be attributed to the genotypes of all 270 individuals.
Fig 3.
Pipeline for ancient haplotype block scan and functional annotation.
(A) Novel procedure for ancient haplotype block scan using HHDs. (B) Functional annotation procedure based on biological pathways. Each box shows materials or tools used in that step.
Fig 4.
Example of ancient haplotype blocks identified in this work.
Four haplotype blocks identified in all three populations (YRI, CEU, and ASN) are shown. The region of overlap between the dashed lines is defined as the ancient haplotype block.
Table 1.
Average length of regions identified by representative methods.
Fig 5.
Distribution of calculated scores.
The x-axis shows the t-statistic score, and the y-axis shows the number of ancient haplotype blocks.
Fig 6.
Classification of ancient haplotype blocks.
Eight clusters of ancient haplotype blocks obtained by clustering based on the network of populations and their t-statistic score profiles. The number on each edge represents the average t-statistic score; smaller scores reflect shorter edges.
Table 2.
Summary of screening results.
Fig 7.
Score distributions for each cluster.
The score distribution of ancient haplotype blocks is shown for each cluster. The clusters can be classified into three groups: I, II, and III. Group I consists of Cluster 1 (blue). Group II consists of Clusters 2, 3, 4, and 5 (red). Group III consists of Clusters 6, 7, and 5′ (green).
Table 3.
Pathways for which the genes in the top 1% of ancient haplotype blocks are enriched.
Fig 8.
Assumed scenarios for the clusters in the top 1% of blocks.
Each node represents a population, and each edge represents the degree of the t-statistic score between two populations. Red, blue, and green nodes represent YRI, CEU, and ASN populations, respectively. Asterisks represent mutations. The mutations were assumed to occur during or after migration, and are represented by asterisks on the arrows or the edges, respectively.