Population genomics of the fission yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe has been widely used as a model eukaryote to study a diverse range of biological processes. However, population genetic studies of this species have been limited to date, and we know very little about the evolutionary processes and selective pressures that are shaping its genome. Here, we sequenced the genomes of 32 worldwide S. pombe strains and examined the pattern of polymorphisms across their genomes. In addition to introns and untranslated regions (UTRs), intergenic regions also exhibited lower levels of nucleotide diversity than synonymous sites, suggesting that a considerable amount of noncoding DNA is under selective constraint and thus likely to be functional. A number of genomic regions showed a reduction of nucleotide diversity probably caused by selective sweeps. We also identified a region close to the end of chromosome 3 where an extremely high level of divergence was observed between 5 of the 32 strains and the remain 27, possibly due to introgression, strong positive selection, or that region being responsible for reproductive isolation. Our study should serve as an important starting point in using a population genomics approach to further elucidate the biology of this important model organism

Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture

(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations

Article The Linkage Method: A Novel Approach for SNP Detection and Haplotype Reconstruction from a Single Diploid Individual Using Next-Generation Sequence Data

Abstract When we sequence a diploid individual, the output actually comprises two genomes: one from the paternal parent and the other from the maternal parent. In this study, we introduce a novel heuristic algorithm for distinguishing singlenucleotide polymorphisms (SNPs) from the two parents and phasing them into haplotypes. The algorithm is unique because it simultaneously performs SNP calling and haplotype phasing. This approach can exploit the linkage information of nearby SNPs, which facilitates the efficient removal of haplotypes that originate from incorrectly mapped short reads. Using simulated data we demonstrated that our approach increased the accuracy of SNP calls. The haplotype reconstruction performance depended largely on the density of SNPs. Using current next-generation sequence technology with a relatively short read length, reasonable performance is expected when this approach is applied to species with an average of five heterozygous sites per 1 kb. The algorithm was implemented as the program "linkSNPs.&quot

Estimating the Time to the Whole-Genome Duplication and the Duration of Concerted Evolution via Gene Conversion in Yeast

A maximum-likelihood (ML) method is developed to estimate the duration of concerted evolution and the time to the whole-genome duplication (WGD) event in baker's yeast (Saccharomyces cerevisiae). The models with concerted evolution fit the data significantly better than the molecular clock model, indicating a crucial role of concerted evolution via gene conversion after gene duplication in yeast. Our ML estimate of the time to the WGD is nearly identical to the time to the speciation event between S. cerevisiae and Kluyveromyces waltii, suggesting that the WGD occurred in very early stages after speciation or the WGD might have been involved in the speciation event

Natural Selection on Gene Order in the Genome Reorganization Process After Whole-Genome Duplication of Yeast

A genome must locate its coding genes on the chromosomes in a meaningful manner with the help of natural selection, but the mechanism of gene order evolution is poorly understood. To explore the role of selection in shaping the current order of coding genes and their cis-regulatory elements, a comparative genomic approach was applied to the baker\u27s yeast Saccharomyces cerevisiae and its close relatives. S. cerevisiae have experienced a whole-genome duplication followed by an extensive reorganization process of gene order, during which a number of new adjacent gene pairs appeared. We found that the proportion of new adjacent gene pairs in divergent orientation is significantly reduced, suggesting that such new divergent gene pairs may be disfavored most likely because their coregulation may be deleterious. It is also found that such new divergent gene pairs have particularly long intergenic regions. These observations suggest that selection specifically worked against deletions in intergenic regions of new divergent gene pairs, perhaps because they should be physically kept away so that they are not coregulated. It is indicated that gene regulation would be one of the major factors to determine the order of coding genes. gene order, whole genome duplication, budding yeast, gene regulation

The linkage method, a novel approach for SNP detection and haplotype reconstruction from a single diploid individual with next generation sequence data

When we sequence a diploid individual, the output actually comprises two genomes: one from the paternal parent and the other from the maternal parent. In this study, we introduce a novel heuristic algorithm for distinguishing single-nucleotide polymorphisms (SNPs) from the two parents and phasing them into haplotypes. The algorithm is unique because it simultaneously performs SNP calling and haplotype phasing. This approach can exploit the linkage information of nearby SNPs, which facilitates the efficient removal of haplotypes that originate from incorrectly mapped short reads. Using simulated data we demonstrated that our approach increased the accuracy of SNP calls. The haplotype reconstruction performance depended largely on the density of SNPs. Using current next-generation sequence technology with a relatively short read length, reasonable performance is expected when this approach is applied to species with an average of five heterozygous sites per 1 kb. The algorithm was implemented as the program “linkSNPs.

Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome

To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q−, 16q−, or HACE1 loss. RFS was better for those with than those without +12 (P = .010) and worse for those with than those without 11q−, 16q−, or HACE1 loss (P = .001, .025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q−, 16q−, or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q−, 16q−, or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q− tumors than in no 16q− tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities

Population Genomics of sub-saharan Drosophila melanogaster: African diversity and non-African admixture.

Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa F(ST) were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations