Author contributions DCJ coordinated all analyses, isolated DNA for sequencing, analysed and filtered SNP calls, conducted diversity analysis and GWAS and drafted the manuscript. CR produced phenotype data for growth on various solid media and growth rates in liquid media. AR conducted analysis of dating using mitochondrial data. DS conducted GWAS. MP analysed all phenotype data. TM identified LTR transposon insertions and analysed transposon insertion data. FXM conducted crosses for analysis of spore viability ZI produced indel calls with Cortex. WL conducted analysis of recombination rate, linkage disequilibrium decay and PCA for distance between strains. TMKC assisted with phenotype and population analysis. RP analysed Cortex and GATK indel calls. MM conducted amino acid profiling. JLDL and AC produced automated measures of cell morphology. SB aligned reads and produced GATK SNP calls. GH analysed population structure using fineSTRUCTURE. BO'F estimated the TMRCA from the nuclear genome using ACG. TK identified LTR transposon insertions JTS produced de novo assemblies. LB developed the custom Workspace workflow Spotsizer. BT assisted with sequence analysis. DAB assisted with analysis of novel genes. TS assisted with strain verification. SC produced images of wild strains and assisted with strain verification. JEEUH assisted with SNP validation. LvT and MT assisted with LTR validation. LJ and JL assisted with manual measures of cell morphology and FACS. SA produced gene expression data. MF, KM and ND assisted with sequencing. WB initiated and assisted with strain collection. JH coordinated manual measures of cell morphology and FACS. RECS coordinated automated measures of cell morphology. MR coordinated amino acid profiling. NM conducted analysis of recombination, linkage disequilibrium and advised on aspects of diversity and GWAS. DJB advised on GWAS. RD facilitated sequencing. JB contributed to the initiation and development of the project and financed the JB laboratory. AccessionsSequence data are archived in the European Nucleotide Archive (www.ebi.ac.uk/ena/), Study Accessions PRJEB2733 and PRJEB6284 (Supplementary Table 7). All SNPs and indels were submitted to NCBI dbSNP (www.ncbi.nlm.nih.gov/SNP/). Accessions are 974514578-974688138 (SNPs) and 974702618-974688139 (indels). Europe PMC Funders Group AbstractNatural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the utility of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, revealing moderate genetic diversity (π = 3 ×10 −3 ) and weak global population structure. We estimate that dispersal of S. pombe began within human antiquity (~340 BCE), and ancestors of these strains reached the Americas at ~1623 CE. We quantified 74 traits, revealing substantial heritable phenotypic diversity. We cond...

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [−13910*T (rs4988235), −13907*G (rs41525747), −13915*G (rs41380347), −14009*G (rs869051967) and −14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the ‘Old World’ and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-017-1847-y) contains supplementary material, which is available to authorized users.

In the budding yeast Saccharomyces cerevisiae, PHO84 and PHO86 are among the genes that are most highly induced in response to phosphate starvation. They are essential for growth when phosphate is limiting, and they function in the high-affinity phosphate uptake system. PHO84 encodes a high-affinity phosphate transporter, and mutations in PHO86 cause many of the same phenotypes as mutations in PHO84, including a phosphate uptake defect and constitutive expression of the secreted acid phosphatase, Pho5p. Here, we show that the subcellular localization of Pho84p is regulated in response to extracellular phosphate levels; it is localized to the plasma membrane in low-phosphate medium but quickly endocytosed and transported to the vacuole upon addition of phosphate to the medium. Moreover, Pho84p is localized to the endoplasmic reticulum (ER) and fails to be targeted to the plasma membrane in the absence of Pho86p. Utilizing an in vitro vesicle budding assay, we demonstrate that Pho86p is required for packaging of Pho84p into COPII vesicles. Pho86p is an ER resident protein, which itself is not transported out of the ER. Interestingly, the requirement of Pho86p for ER exit is specific to Pho84p, because other members of the hexose transporter family to which Pho84 belongs are not mislocalized in the absence of Pho86p.