Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only ∼200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.

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...

Large structural variations (SVs) within genomes are more challenging to identify than smaller genetic variants but may substantially contribute to phenotypic diversity and evolution. We analyse the effects of SVs on gene expression, quantitative traits and intrinsic reproductive isolation in the yeast Schizosaccharomyces pombe. We establish a high-quality curated catalogue of SVs in the genomes of a worldwide library of S. pombe strains, including duplications, deletions, inversions and translocations. We show that copy number variants (CNVs) show a variety of genetic signals consistent with rapid turnover. These transient CNVs produce stoichiometric effects on gene expression both within and outside the duplicated regions. CNVs make substantial contributions to quantitative traits, most notably intracellular amino acid concentrations, growth under stress and sugar utilization in winemaking, whereas rearrangements are strongly associated with reproductive isolation. Collectively, these findings have broad implications for evolution and for our understanding of quantitative traits including complex human diseases.

No abstract

We describe a sequential (step by step) Darwinian model for the evolution of life from the late stages of the RNA world through to the emergence of eukaryotes and prokaryotes. The starting point is our model, derived from current RNA activity, of the RNA world just prior to the advent of genetically-encoded protein synthesis. By focusing on the function of the protoribosome we develop a plausible model for the evolution of a protein-synthesizing ribosome from a high-fidelity RNA polymerase that incorporated triplets of oligonucleotides. With the standard assumption that during the evolution of enzymatic activity, catalysis is transferred from RNA --> RNP --> protein, the first proteins in the "breakthrough organism" (the first to have encoded protein synthesis) would be nonspecific chaperone-like proteins rather than catalytic. Moreover, because some RNA molecules that pre-date protein synthesis under this model now occur as introns in some of the very earliest proteins, the model predicts these particular introns are older than the exons surrounding them, the "introns-first" theory. Many features of the model for the genome organization in the final RNA world ribo-organism are more prevalent in the eukaryotic genome and we suggest that the prokaryotic genome organization (a single, circular genome with one center of replication) was derived from a "eukaryotic-like" genome organization (a fragmented linear genome with multiple centers of replication). The steps from the proposed ribo-organism RNA genome --> eukaryotic-like DNA genome --> prokaryotic-like DNA genome are all relatively straightforward, whereas the transition prokaryotic-like genome --> eukaryotic-like genome appears impossible under a Darwinian mechanism of evolution, given the assumption of the transition RNA --> RNP --> protein. A likely molecular mechanism, "plasmid transfer," is available for the origin of prokaryotic-type genomes from an eukaryotic-like architecture. Under this model prokaryotes are considered specialized and derived with reduced dependence on ssRNA biochemistry. A functional explanation is that prokaryote ancestors underwent selection for thermophily (high temperature) and/or for rapid reproduction (r selection) at least once in their history.

No abstract

Large structural variations (SVs) in the genome are harder to identify than smaller genetic variants but may substantially contribute to phenotypic diversity and evolution. Here we analyze the effects of SVs on gene expression, quantitative traits, and intrinsic reproductive isolation in the yeast Schizosaccharomyces pombe. We establish a high-quality curated catalog of SVs in the genomes of a worldwide library of S. pombe strains, including duplications, deletions, inversions and translocations. We show that copy number variants (CNVs) frequently segregate within closely related clonal populations, are weakly linked to single nucleotide polymorphisms (SNPs), and show other genetic signals consistent with rapid turnover. These transient CNVs produce stoichiometric effects on gene expression both within and outside the duplicated regions. CNVs make substantial contributions to quantitative traits such as cell shape, cell growth under diverse conditions, sugar utilization in winemaking, whereas rearrangements are strongly associated with reproductive isolation. Collectively, these findings have broad implications for evolution and for our understanding of quantitative traits including complex human diseases.

An RNA world is widely accepted as a probable stage in the early evolution of life. Two implications are that proteins have gradually replaced RNA as the main biological catalysts and that RNA has not taken on any major de novo catalytic function after the evolution of protein synthesis, that is, there is an essentially irreversible series of steps RNA --> RNP --> protein. This transition, as expected from a consideration of catalytic perfection, is essentially complete for reactions when the substrates are small molecules. Based on these principles we derive criteria for identifying RNAs in modern organisms that are relics from the RNA world and then examine the function and phylogenetic distribution of RNA for such remnants of the RNA world. This allows an estimate of the minimum complexity of the last ribo-organism-the stage just preceding the advent of genetically encoded protein synthesis. Despite the constraints placed on its size by a low fidelity of replication (the Eigen limit), we conclude that the genome of this organism reached a considerable level of complexity that included several RNA-processing steps. It would include a large protoribosome with many smaller RNAs involved in its assembly, pre-tRNAs and tRNA processing, an ability for recombination of RNA, some RNA editing, an ability to copy to the end of each RNA strand, and some transport functions. It is harder to recognize specific metabolic reactions that must have existed but synthetic and bio-energetic functions would be necessary. Overall, this requires that such an organism maintained a multiple copy, double-stranded linear RNA genome capable of recombination and splicing. The genome was most likely fragmented, allowing each "chromosome" to be replicated with minimum error, that is, within the Eigen limit. The model as developed serves as an outgroup to root the tree of life and is an alternative to using sequence data for inferring properties of the earliest cells.