Michael Lynch

Indiana University Bloomington, Bloomington, Indiana, United States

Are you Michael Lynch?

Claim your profile

Publications (206)1651.21 Total impact

  • Source

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Caedibacter varicaedens is a kappa killer endosymbiont bacterium of the ciliate Paramecium biaurelia . Here, we present the draft genome sequence of C. varicaedens .
    Genome Announcements 11/2015; 3(6). DOI:10.1128/genomeA.01310-15
  • [Show abstract] [Hide abstract]
    ABSTRACT: Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally-heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (~4 x 10-9 per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.
    Genome Research 10/2015; DOI:10.1101/gr.191338.115 · 14.63 Impact Factor
  • Source

  • Source

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hybridization plays a potentially important role in the origin of obligate parthenogenesis (OP) in many organisms. However, it remains controversial whether hybridization directly triggers the transition from sexual reproduction to obligate asexuality or a hybrid genetic background enables asexual species to persist. Furthermore, we know little about the specific genetic elements from the divergent, yet still hybridizing lineages responsible for this transition and how these elements are further spread to create other OP lineages. In this study, we address these questions in Daphnia pulex, where cyclically parthenogenetic (CP) and OP lineages coexist. Ancestry estimates and whole-genome association mapping using 32 OP isolates suggest that a complex hybridization history between the parental species D. pulex and D. pulicaria is responsible for the introgression of a set of 647 D. pulicaria SNP alleles that show perfect association with OP. Crossing experiments using males of OP lineages and females of CP lineages strongly support a polygenic basis for OP. Single-sperm analyses show that although normal meiotic recombination occurs in the production of haploid sperm by males of OP lineages, a significant proportion of such sperm are polyploid, suggesting that the spread of asexual elements via these males (i.e., contagious asexuality) is much less efficient than previously envisioned. Although the current Daphnia genome annotation does not provide mechanistic insight into the nature of the asexuality-associated alleles, these alleles should be considered as candidates for future investigations on the genetic underpinnings of OP.
    Molecular Biology and Evolution 09/2015; DOI:10.1093/molbev/msv190 · 9.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an ~1700 generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 indels across the 96 replicates. This equates to a base substitution mutation rate of 2.00 x 10(-10) mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome, and suggests that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeast. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation. Copyright © 2015, The Genetics Society of America.
    Genetics 08/2015; 201(2). DOI:10.1534/genetics.115.177329 · 5.96 Impact Factor
  • Source

    Genetics 07/2015; 201(2):737-744. · 5.96 Impact Factor
  • Source
    Takahiro Maruki · Michael Lynch ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapidly improving high-throughput sequencing technologies provide unprecedented opportunities for carrying out population-genomic studies with various organisms. To take full advantage of these methods, it is essential to correctly estimate allele and genotype frequencies, and here we present a maximum-likelihood method that accomplishes these tasks. The proposed method fully accounts for uncertainties resulting from sequencing errors and biparental chromosome sampling, and yields essentially unbiased estimates with minimal sampling variances with moderately high depths of coverage regardless of a mating system and structure of the population. Moreover, we have developed statistical tests for examining the significance of polymorphisms and their genotypic deviations from Hardy-Weinberg equilibrium. We examine the performance of the proposed method by computer simulations and apply it to low-coverage human data generated by high-throughput sequencing. The results show that the proposed method improves our ability to carry out population-genomic analyses in important ways. The software package of the proposed method is freely available from https://github.com/Takahiro-Maruki/Package-GFE. Copyright © 2015, The Genetics Society of America.
    Genetics 07/2015; 201(2). DOI:10.1534/genetics.115.179077 · 5.96 Impact Factor
  • Source
    Dataset: Figure S2

  • Source

  • Source
    Dataset: Figure S1

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic linkage maps are critical for assembling draft genomes to a meaningful chromosome level and for deciphering the genomic underpinnings of biological traits. The estimates of recombination rates derived from genetic maps also play an important role in understanding multiple aspects of genomic evolution such as nucleotide substitution patterns and accumulation of deleterious mutations. In this study, we developed a high-throughput experimental approach that combines fluorescence-activated cell sorting, whole-genome amplification, and short-read sequencing to construct a genetic map using single sperm cells. Furthermore, a computational algorithm was developed to analyze single sperm whole-genome sequencing data for map construction. These methods allowed us to rapidly build a male-specific genetic map for the freshwater microcrustacean Daphnia pulex, which shows significant improvements compared to a previous map. With a total of mapped 1672 haplotype blocks and an average intermarker distance of 0.87 cM, this map spans a total genetic distance of 1451 Kosambi cM and comprises 90% of the resolved regions in the current Daphnia reference assembly. The map also reveals the mistaken mapping of seven scaffolds in the reference assembly onto chromosome II by a previous microsatellite map based on F2 crosses. Our approach can be easily applied to many other organisms and holds great promise for unveiling the intragenomic and intraspecific variation in the recombination rates. Copyright © 2015, The Genetics Society of America.
    Genetics 06/2015; 201(1). DOI:10.1534/genetics.115.179028 · 5.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deinococcus bacteria are extremely resistant to radiation, oxidation, and desiccation. Resilience to these factors has been suggested to be due to enhanced damage prevention and repair mechanisms, as well as highly efficient antioxidant protection systems. Here, using mutation-accumulation experiments we find that the GC-rich Deinococcus radiodurans has an overall background genomic mutation rate similar to that of E. coli, but differs in mutation spectrum, with the A/T to G/C mutation rate (based on a total count of 88 A:T→G:C transitions and 82 A:T→C:G transversions) per site per generation higher than that in the other direction (based on a total count of 157 G:C→A:T transitions and 33 G:C→T:A transversions). We propose that this unique spectrum is shaped mainly by the abundant uracil DNA glycosylases (UDG) reducing G:C→T:A transversions, adenine methylation elevating A:T→C:G transversions, and absence of cytosine methylation decreasing G:C→A:T transitions. As opposed to the >100× elevation of the mutation rate in MMR(-) strains of most other organisms, MMR(-) D. radiodurans only exhibits a four-fold elevation, raising the possibility that other DNA repair mechanisms compensate for a relatively low-efficiency DNA mismatch repair pathway. Since D. radiodurans has plentiful insertion sequence (IS) elements in the genome and the activities of IS elements are rarely directly explored, we also estimated the insertion (transposition) rate of the IS elements to be 2.50 × 10(-3) per genome per generation in the wild-type strain; knocking out MMR did not elevate the IS element insertion rate in this organism. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Molecular Biology and Evolution 05/2015; 32(9). DOI:10.1093/molbev/msv119 · 9.11 Impact Factor
  • Source

    Molecular Biology and Evolution 05/2015; 32(9):2383-2392. · 9.11 Impact Factor
  • Marcus M Dillon · Way Sung · Michael Lynch · Vaughn S Cooper ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Spontaneous mutations are ultimately essential for evolutionary change and are also the root cause of many diseases. However, until recently, both biological and technical barriers have prevented detailed analyses of mutation profiles, constraining our understanding of the mutation process to a few model organisms and leaving major gaps in our understanding of the role of genome content and structure on mutation. Here, we present a genome-wide view of the molecular mutation spectrum in Burkholderia cenocepacia, a clinically relevant pathogen with high %GC-content and multiple chromosomes. We find that B. cenocepacia has low genome-wide mutation rates with insertion-deletion mutations biased towards deletions, consistent with the idea that deletion pressure reduces prokaryotic genome sizes. Unlike prior studies of other organisms, mutations in B. cenocepacia are not AT-biased, which suggests that at least some genomes with high %GC-content experience unusual base-substitution mutation pressure. Importantly, we also observe variation in both the rates and spectra of mutations among chromosomes and elevated G:C>T:A transversions in late-replicating regions. Thus, although some patterns of mutation appear to be highly conserved across cellular life, others vary between species and even between chromosomes of the same species, potentially influencing the evolution of nucleotide composition and genome architecture. Copyright © 2015, The Genetics Society of America.
    Genetics 05/2015; 200(3). DOI:10.1534/genetics.115.176834 · 5.96 Impact Factor
  • Jean-Francois Gout · Michael Lynch ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Whole-Genome Duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful while others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift towards uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Molecular Biology and Evolution 04/2015; 32(8). DOI:10.1093/molbev/msv095 · 9.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the general assumption that site-specific mutation rates are independent of the local sequence context, a growing body of evidence suggests otherwise. To further examine context-dependent patterns of mutation, we amassed 5645 spontaneous mutations in wild-type and mismatch-repair deficient mutation accumulation lines of the gram-positive model organism Bacillus subtilis. We then analysed > 7500 spontaneous base-substitution mutations across Bacillus subtilis, Escherichia coli, and Mesoplasma florum wild-type and mismatch-repair deficient mutation-accumulation lines, finding a context-dependent mutation pattern that is asymmetric around the origin of replication. Different neighbouring nucleotides can alter site-specific mutation rates by as much as 75-fold, with sites neighbouring G:C base pairs or dimers involving alternating pyrimidine-purine and purine-pyrimidine nucleotides having significantly elevated mutation rates. The influence of context-dependent mutation on genome architecture is strongest in M. florum, consistent with the reduced efficiency of selection in organisms with low effective population size. If not properly accounted for, the disparities arising from patterns of context-dependent mutation can significantly influence interpretations of positive and purifying selection. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2015. This work is written by US Government employees and is in the public domain in the US.
    Molecular Biology and Evolution 03/2015; 32(7). DOI:10.1093/molbev/msv055 · 9.11 Impact Factor
  • Source

  • Source

Publication Stats

19k Citations
1,651.21 Total Impact Points


  • 2001-2015
    • Indiana University Bloomington
      • Department of Biology
      Bloomington, Indiana, United States
  • 2008
    • The University of Edinburgh
      • Institute of Evolutionary Biology
      Edinburgh, Scotland, United Kingdom
    • Saint Petersburg State University
      • Faculty of Biology and Soil Science
      Sankt-Peterburg, St.-Petersburg, Russia
    • University of Windsor
      • Great Lakes Institute for Environmental Research
      Windsor, Ontario, Canada
  • 2007
    • University of Leipzig
      • Institute of Biology
      Leipzig, Saxony, Germany
  • 2006
    • University of New Mexico
      • Department of Biology
      Albuquerque, New Mexico, United States
  • 1990-2004
    • University of Oregon
      • • Center for Ecology and Evolutionary Biology
      • • Computational Science Institute
      • • Department of Biology
      Eugene, OR, United States
  • 2000
    • National Center for Genome Resources
      Santa Fe, New Mexico, United States
  • 1987-1989
    • University of Illinois, Urbana-Champaign
      Urbana, Illinois, United States