Discovery and genotyping of genome structural polymorphism by sequencing on a population scale

Accurate and complete analysis of genome variation in large populations will be required to understand the role of genome variation in complex disease. We present an analytical framework for characterizing genome deletion polymorphism in populations using sequence data that are distributed across hundreds or thousands of genomes. Our approach uses population-level concepts to reinterpret the technical features of sequence data that often reflect structural variation. In the 1000 Genomes Project pilot, this approach identified deletion polymorphism across 168 genomes (sequenced at 4 × average coverage) with sensitivity and specificity unmatched by other algorithms. We also describe a way to determine the allelic state or genotype of each deletion polymorphism in each genome; the 1000 Genomes Project used this approach to type 13,826 deletion polymorphisms (48-995,664 bp) at high accuracy in populations. These methods offer a way to relate genome structural polymorphism to complex disease in populations.     

Chance and necessity in the evolution of a bacterial pathogen

The combination of genomic, epidemiological and evolutionary analyses provides a powerful toolbox for understanding how pathogens adapt to their human hosts. By sequencing 112 Burkholderia dolosa genomes from an outbreak among patients with cystic fibrosis, a new study documents evolution in action and identifies a set of genes that contributed to the pathogen's adaptation.     

Reductive evolution suggested from the complete genome sequence of a plant-pathogenic phytoplasma

The minimal gene set essential for life has long been sought. We report the 860-kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer metabolic functions than do mycoplasma genomes. It lacks the pentose phosphate cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be essential for life. This may be the result of reductive evolution as a consequence of life as an intracellular parasite in a nutrient-rich environment.     

Adaptation shapes patterns of genome evolution on sexual and asexual chromosomes in Drosophila

What advantage might sexual recombination confer? Population genetics theory predicts that asexual genomes are less efficient at eliminating deleterious mutations and incorporating beneficial alleles. Here, I compare patterns of genome evolution in a 40-kb gene-rich region on homologous neo-sex chromosomes of Drosophila miranda. Genes on the non-recombining neo-Y show various signs of degeneration, including transposable-element insertions, frameshift mutations and a higher rate of amino-acid substitution. In contrast, loci on the recombining neo-X show intact open reading frames and generally low rates of amino-acid substitution. One exceptional gene on the neo-X shows evidence for adaptive protein evolution, affecting patterns of variability at neighboring regions along the chromosome. These findings illustrate the limits to natural selection in an asexual genome. Deleterious mutations, including repetitive DNA, accumulate on a non-recombining chromosome, whereas rapid protein evolution due to positive selection is confined to the recombining homolog.     

Pervasive joint influence of epistasis and plasticity on mutational effects in Escherichia coli

The effects of mutations on phenotype and fitness may depend on the environment (phenotypic plasticity), other mutations (genetic epistasis) or both. Here we examine the fitness effects of 18 random insertion mutations in E. coli in two resource environments and five genetic backgrounds. We tested each mutation for plasticity and epistasis by comparing its fitness effects across these ecological and genetic contexts. Some mutations had no measurable effect in any of these contexts. None of the mutations had effects on phenotypic plasticity that were independent of genetic background. However, half the mutations had epistatic interactions such that their effects differed among genetic backgrounds, usually in an environment-dependent manner. Also, the pattern of mutational effects across backgrounds indicated that epistasis had been shaped primarily by unique events in the evolutionary history of a population rather than by repeatable events associated with shared environmental history.