Genome duplications are important evolutionary events that impact the rate and spectrum of beneficial mutations and thus the rate of adaptation. Laboratory evolution experiments initiated with haploid Saccharomyces cerevisiae cultures repeatedly experience whole-genome duplication (WGD). We report recurrent genome duplication in 46 haploid yeast populations evolved for 4,000 generations. We find that WGD confers a fitness advantage, and this immediate fitness gain is accompanied by a shift in genomic and phenotypic evolution. The presence of ploidy-enriched targets of selection and structural variants reveals that autodiploids utilize adaptive paths inaccessible to haploids. We find that autodiploids accumulate recessive deleterious mutations, indicating an increased susceptibility for nonadaptive evolution. Finally, we report that WGD results in a reduced adaptation rate, indicating a trade-off between immediate fitness gains and long-term adaptability.

Bacteria may become genetically and phenotypically diverse during long-term colonization of cystic fibrosis (CF) patient lungs, yet our understanding of within-host evolutionary processes during these infections is lacking. Here we combined current genome sequencing technologies and detailed phenotypic profiling of the opportunistic pathogen Burkholderia multivorans using sequential isolates sampled from a CF patient over 20 years. The evolutionary history of these isolates highlighted bacterial genes and pathways that were likely subject to strong selection within the host and were associated with altered phenotypes, such as biofilm production, motility, and antimicrobial resistance. Importantly, multiple lineages coexisted for years or even decades within the infection, and the period of diversification within the dominant lineage was associated with deterioration of the patient’s lung function. Identifying traits under strong selection during chronic infection not only sheds new light onto Burkholderia evolution but also sets the stage for tailored therapeutics targeting the prevailing lineages associated with disease progression.

Congenital muscular dystrophy (CMD) 3 is a heterogeneous group of inherited neuromuscular disorders characterized by severe muscle weakness, ocular and neuronal migration abnormalities, and variable mental retardation (1). Within recent years, it has become increasing clear through genetic studies that hypoglycosylation of the protein dystroglycan (DG) is a commonality in many forms of CMD (the so-called dystroglycanopathies). DG is post-translationally cleaved into an extracellular ␣-DG subunit and a transmembrane ␤-DG subunit (2). ␣-DG is a key component of the dystrophin-glycoprotein complex that serves as a link between the cytoskeleton of cells and the extracellular matrix by binding to proteins such as laminin (3). Interaction between ␣-DG and its extracellular ligands requires ␣-DG to be properly post-translationally modified through the addition of O-linked oligosaccharides, specifically O-mannose (4, 5). To date, mutations in six genes that encode determined or predicted glycosyltransferases have been shown to result in varying forms of CMD in which the post-translational processing of ␣-DG is affected (4 -6). The six mutated genes and their original resulting form of CMD are as follows: POMT1 (protein O-mannosyltransferase 1) and POMT2, Walker-Warburg syndrome (7,8); POMGnT1 (protein Olinked mannose ␤1,2-N-acetylglucosaminyltransferase 1), muscle-eye-brain disease (9); fukutin, Fukuyama congenital muscular dystrophy (10); FKRP (fukutin-related protein), congenital muscular dystrophy 1C (11); and LARGE, congenital muscular dystrophy 1D (12). Recent work has demonstrated that selected mutations in some of these genes can cause various forms of CMD that are likely dependent on the severity of the mutation on enzymatic activity and stability (13). Abnormal glycosylation of ␣-DG appears to be a commonality among all of the aforementioned forms of CMD. Although expression of ␣-DG appears not to be grossly affected, the ability of ␣-DG to be recognized by monoclonal antibodies IIH6 and VIA4 1 is eliminated, as is the ability of ␣-DG to properly bind its ligands (14).␣-DG is composed of a central mucin-like region that is extensively heterogeneously glycosylated with glycan chains that are initiated by both O-

Ploidy varies considerably in nature. However, our understanding of the impact of ploidy on adaptation is incomplete. Many microbial evolution experiments characterize adaptation in haploid organisms, but few focus on diploid organisms. Here, we perform a 4,000-generation evolution experiment using diploid strains of the yeast Saccharomyces cerevisiae. We show that the rate of adaptation and spectrum of beneficial mutations are influenced by ploidy. Haldane's sieve effectively alters access to recessive beneficial mutations in diploid populations, leading to a slower rate of adaptation and a spectrum of beneficial mutations that is shifted towards dominant mutations. Genomic position also has an important role, as the prevalence of homozygous mutations is largely dependent on their proximity to a recombination hotspot. Our results demonstrate key aspects of diploid adaptation that have previously been understudied and provide support for several proposed theories.

Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we use a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally evolved yeast populations. We report that nearly 80% of detected mutations have no discernible effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intracohort synergistic epistasis between alleles of hsl7 and kel1, which arose together in a low-frequency lineage.experimental evolution | cohorts | fitness | epistasis A daptation is a fundamental biological process. The identification and characterization of the genetic mechanisms underlying adaptive evolution remains a central challenge in biology. To identify beneficial mutations, recent studies have characterized thousands of first-step mutations and systematic deletion and amplification mutations in the yeast genome (1, 2). These unbiased screens provide a wealth of information regarding the spectrum of beneficial mutations, their fitness effects, and the biological processes under selection. However, this information alone cannot predict which mutations will ultimately succeed in an evolutionary context as genetic interactions and population dynamics also impart substantial influence on the adaptive outcomes.Early theoretical models assume that beneficial mutations are rare, such that once a beneficial mutation escapes drift, it will fix (3-5). For most microbial populations, however, multiple beneficial mutations will arise and spread simultaneously, leading to complex dynamics of clonal interference and genetic hitchhiking (6-9), and in many cases, multiple mutations track tightly with one another through time as mutational cohorts (10-13). The fate of each mutation is therefore dependent not only on its own fitness effect, but on the fitness effects of and interactions between all mutations in the population. Many beneficial mutations will be lost due to drift and clonal interference, whereas many neutral (and even deleterious) mutations will fix by hitchhiking. The influence of clonal interference and genetic hitchhiking on the success of mutations makes it difficult to identify beneficial mutations from sequenced clones or population samples. The extent of genetic hitchhiking and its evolutionary significanc...