Michael Lynch

Indiana University Bloomington, Bloomington, Indiana, United States

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Publications (215)1724.43 Total impact

  • Michael Lynch · Georgi K. Marinov

    No preview · Article · Jan 2016 · Proceedings of the National Academy of Sciences
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    Georgi K Marinov · Michael Lynch
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    ABSTRACT: Histone proteins and the nucleosomal organization of chromatin are near-universal eukaroytic features, with the exception of dinoflagellates. Previous studies have suggested that histones do not play a major role in the packaging of dinoflagellate genomes, although several genomic and transcriptomic surveys have detected a full set of core histone genes. Here, transcriptomic and genomic sequence data from multiple dinoflagellate lineages are analyzed, and the diversity of histone proteins and their variants characterized, with particular focus on their potential posttranslational modifications and the conservation of the histone code. In addition, the set of putative epigenetic mark readers and writers, chromatin remodelers and histone chaperones are examined. Dinoflagellates clearly express the most derived set of histones among all autonomous eukaryote nuclei, consistent with a combination of relaxation of sequence con-straints imposed by the histone code and the presence of numerous specialized histone variants. The histone code itself appears to have diverged significantly in some of its compo-nents, yet others are conserved, implying conservation of the associated biochemical processes. Specifically, and with major implications for the function of histones in dinoflagellates, the results presented here strongly suggest that transcription through nucleosomal arrays happens in dinoflagellates. Finally, the plausible roles of histones in dinoflagellate nuclei are discussed.
    Preview · Article · Dec 2015 · G3-Genes Genomes Genetics
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Caedibacter varicaedens is a kappa killer endosymbiont bacterium of the ciliate Paramecium biaurelia . Here, we present the draft genome sequence of C. varicaedens .
    Full-text · Article · Nov 2015 · Genome Announcements
  • Michael Lynch · Georgi K. Marinov
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    ABSTRACT: An enduring mystery of evolutionary genomics concerns the mechanisms responsible for lineage-specific expansions of genome size in eukaryotes, especially in multicellular species. One idea is that all excess DNA is mutationally hazardous, but weakly enough so that genome-size expansion passively emerges in species experiencing relatively low efficiency of selection owing to small effective population sizes. Another idea is that substantial gene additions were impossible without the energetic boost provided by the colonizing mitochondrion in the eukaryotic lineage. Contrary to this latter view, analysis of cellular energetics and genomics data from a wide variety of species indicates that, relative to the lifetime ATP requirements of a cell, the costs of a gene at the DNA, RNA, and protein levels decline with cell volume in both bacteria and eukaryotes. Moreover, these costs are usually sufficiently large to be perceived by natural selection in bacterial populations, but not in eukaryotes experiencing high levels of random genetic drift. Thus, for scaling reasons that are not yet understood, by virtue of their large size alone, eukaryotic cells are subject to a broader set of opportunities for the colonization of novel genes manifesting weakly advantageous or even transiently disadvantageous phenotypic effects. These results indicate that the origin of the mitochondrion was not a prerequisite for genome-size expansion.
    No preview · Article · Nov 2015 · Proceedings of the National Academy of Sciences
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    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.
    No preview · Article · Oct 2015 · Genome Research
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    Full-text · Dataset · Oct 2015
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    Full-text · Dataset · Oct 2015
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    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 single nucleotide polymorphism 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 through 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.
    Full-text · Article · Sep 2015 · Molecular Biology and Evolution
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    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.
    Full-text · Article · Aug 2015 · Genetics
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    Full-text · Article · Jul 2015 · Genetics
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    Takahiro Maruki · Michael Lynch
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    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.
    Preview · Article · Jul 2015 · Genetics
  • Michael Lynch

    No preview · Article · Jul 2015 · Nature
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    Full-text · Dataset · Jul 2015
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    Dataset: Figure S1

    Full-text · Dataset · Jul 2015
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    Dataset: Figure S2

    Full-text · Dataset · Jul 2015
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    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.
    Full-text · Article · Jun 2015 · Genetics
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    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.
    Full-text · Article · May 2015 · Molecular Biology and Evolution
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    Full-text · Article · May 2015 · Molecular Biology and Evolution
  • Marcus M Dillon · Way Sung · Michael Lynch · Vaughn S Cooper
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    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.
    No preview · Article · May 2015 · Genetics

Publication Stats

20k Citations
1,724.43 Total Impact Points

Institutions

  • 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
  • 1990-2008
    • University of Windsor
      • • Great Lakes Institute for Environmental Research
      • • Department of Biological Sciences
      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