Undersampling Genomes has Biased Time and Rate Estimates Throughout the Tree of Life

Tue, 11 Sep 2018 00:00:00 GMT

Julie Marin and S. Blair Hedges

Patterns of Ancestral Animal Codon Usage Bias Revealed through Holozoan Protists

Wed, 29 Aug 2018 00:00:00 GMT

Choanoflagellates and filastereans are the closest known single celled relatives of Metazoa within Holozoa and provide insight into how animals evolved from their unicellular ancestors. Codon usage bias has been extensively studied in metazoans, with both natural selection and mutation pressure playing important roles in different species. The disparate nature of metazoan codon usage patterns prevents the reconstruction of ancestral traits. However, traits conserved across holozoan protists highlight characteristics in the unicellular ancestors of Metazoa. Presented here are the patterns of codon usage in the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta, as well as the filasterean Capsaspora owczarzaki. Codon usage is shown to be remarkably conserved. Highly biased genes preferentially use GC-ending codons, however there is limited evidence this is driven by local mutation pressure. The analyses presented provide strong evidence that natural selection, for both translational accuracy and efficiency, dominates codon usage bias in holozoan protists. In particular, the signature of selection for translational accuracy can be detected even in the most weakly biased genes. Biased codon usage is shown to have coevolved with the tRNA species, with optimal codons showing complementary binding to the highest copy number tRNA genes. Furthermore, tRNA modification is shown to be a common feature for amino acids with higher levels of degeneracy and highly biased genes show a strong preference for using modified tRNAs in translation. The translationally optimal codons defined here will be of benefit to future transgenics work in holozoan protists, as their use should maximise protein yields from edited transgenes.

MACSE v2: Toolkit for the Alignment of Coding Sequences Accounting for Frameshifts and Stop Codons

Sat, 25 Aug 2018 00:00:00 GMT

Multiple sequence alignment is a prerequisite for many evolutionary analyses. Multiple Alignment of Coding Sequences (MACSE) is a multiple sequence alignment program that explicitly accounts for the underlying codon structure of protein-coding nucleotide sequences. Its unique characteristic allows building reliable codon alignments even in the presence of frameshifts. This facilitates downstream analyses such as selection pressure estimation based on the ratio of nonsynonymous to synonymous substitutions. Here, we present MACSE v2, a major update with an improved version of the initial algorithm enriched with a complete toolkit to handle multiple alignments of protein-coding sequences. A graphical interface now provides user-friendly access to the different subprograms.

Xenacoelomorph Neuropeptidomes Reveal a Major Expansion of Neuropeptide Systems during Early Bilaterian Evolution

Fri, 24 Aug 2018 00:00:00 GMT

Neuropeptides are neurosecretory signaling molecules in protostomes and deuterostomes (together Nephrozoa). Little, however, is known about the neuropeptide complement of the sister group of Nephrozoa, the Xenacoelomorpha, which together form the Bilateria. Because members of the xenacoelomorph clades Xenoturbella, Nemertodermatida, and Acoela differ extensively in their central nervous system anatomy, the reconstruction of the xenacoelomorph and bilaterian neuropeptide complements may provide insights into the relationship between nervous system evolution and peptidergic signaling. Here, we analyzed transcriptomes of seven acoels, four nemertodermatids, and two Xenoturbella species using motif searches, similarity searches, mass spectrometry and phylogenetic analyses to characterize neuropeptide precursors and neuropeptide receptors. Our comparison of these repertoires with previously reported nephrozoan and cnidarian sequences shows that the majority of annotated neuropeptide GPCRs in cnidarians are not orthologs of specific bilaterian neuropeptide receptors, which suggests that most of the bilaterian neuropeptide systems evolved after the cnidarian–bilaterian evolutionary split. This expansion of more than 20 peptidergic systems in the stem leading to the Bilateria predates the evolution of complex nephrozoan organs and nervous system architectures. From this ancient set of neuropeptides, acoels show frequent losses that correlate with their divergent central nervous system anatomy. We furthermore detected the emergence of novel neuropeptides in xenacoelomorphs and their expansion along the nemertodermatid and acoel lineages, the two clades that evolved nervous system condensations. Together, our study provides fundamental insights into the early evolution of the bilaterian peptidergic systems, which will guide future functional and comparative studies of bilaterian nervous systems.

Limited Evidence for Parallel Molecular Adaptations Associated with the Subterranean Niche in Mammals: A Comparative Study of Three Superorders

Mon, 20 Aug 2018 00:00:00 GMT

Among mammals, several lineages have independently adapted to a subterranean niche and possess similar phenotypic traits for burrowing (e.g., cylindrical bodies, short limbs, and absent pinnae). Previous research on mole-rats has revealed molecular adaptations for coping with reduced oxygen, elevated carbon dioxide, and the absence of light. In contrast, almost nothing is known regarding molecular adaptations in other subterranean lineages (e.g., true moles and golden moles). Therefore, the extent to which the recurrent phenotypic adaptations of divergent subterranean taxa have arisen via parallel routes of molecular evolution remains untested. To address these issues, we analyzed ∼8,000 loci in 15 representative subterranean taxa of four independent transitions to an underground niche for signatures of positive selection and convergent amino acid substitutions. Complementary analyses were performed in nonsubterranean “control” taxa to assess the biological significance of results. We found comparable numbers of positively selected genes in each of the four subterranean groups; however, correspondence in terms of gene identity between gene sets was low. Furthermore, we did not detect evidence of more convergent amino acids among subterranean species pairs compared with levels found between nonsubterranean controls. Comparisons with nonsubterranean taxa also revealed loci either under positive selection or with convergent substitutions, with similar functional enrichment (e.g., cell adhesion, immune response, and coagulation). Given the limited indication that positive selection and convergence occurred in the same loci, we conclude that selection may have acted on different loci across subterranean mammal lineages to produce similar phenotypes.

Genomics of Parallel Ecological Speciation in Lake Victoria Cichlids

Tue, 14 Aug 2018 00:00:00 GMT

Joana Isabel Meier, David Alexander Marques, Catherine Elise Wagner, Laurent Excoffier, and Ole Seehausen

Coalescent Analysis of Phylogenomic Data Confidently Resolves the Species Relationships in the Anopheles gambiae Species Complex

Thu, 09 Aug 2018 00:00:00 GMT

Deep coalescence and introgression make it challenging to infer phylogenetic relationships among closely related species that arose through radiative speciation events. Despite numerous phylogenetic analyses and the availability of whole genomes, the phylogeny in the Anopheles gambiae species complex has not been confidently resolved. Here we extract over 80, 000 coding and noncoding short segments (called loci) from the genomes of six members of the species complex and use a Bayesian method under the multispecies coalescent model to infer the species tree, which takes into account genealogical heterogeneity across the genome and uncertainty in the gene trees. We obtained a robust estimate of the species tree from the distal region of the X chromosome: (A. merus, ((A. melas, (A. arabiensis, A. quadriannulatus)), (A. gambiae, A. coluzzii))), with A. merus to be the earliest branching species. This species tree agrees with the chromosome inversion phylogeny and provides a parsimonious interpretation of inversion and introgression events. Simulation informed by the real data suggest that the coalescent approach is reliable while the sliding-window analysis used in a previous phylogenomic study generates artifactual species trees. Likelihood ratio test of gene flow revealed strong evidence of autosomal introgression from A. arabiensis into A. gambiae (at the average rate of ∼0.2 migrants per generation), but not in the opposite direction, and introgression of the 3 L chromosomal region from A. merus into A. quadriannulatus. Our results highlight the importance of accommodating incomplete lineage sorting and introgression in phylogenomic analyses of species that arose through recent radiative speciation events.

A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences

Tue, 07 Aug 2018 00:00:00 GMT

Overlapping genes in viruses maximize the coding capacity of their genomes and allow the generation of new genes without major increases in genome size. Despite their importance, the evolution and function of overlapping genes are often not well understood, in part due to difficulties in their detection. In addition, most bioinformatic approaches for the detection of overlapping genes require the comparison of multiple genome sequences that may not be available in metagenomic surveys of virus biodiversity. We introduce a simple new method for identifying candidate functional overlapping genes using single virus genome sequences. Our method uses randomization tests to estimate the expected length of open reading frames and then identifies overlapping open reading frames that significantly exceed this length and are thus predicted to be functional. We applied this method to 2548 reference RNA virus genomes and find that it has both high sensitivity and low false discovery for genes that overlap by at least 50 nucleotides. Notably, this analysis provided evidence for 29 previously undiscovered functional overlapping genes, some of which are coded in the antisense direction suggesting there are limitations in our current understanding of RNA virus replication.

A Maximum-Likelihood Approach to Estimating the Insertion Frequencies of Transposable Elements from Population Sequencing Data

Tue, 07 Aug 2018 00:00:00 GMT

Transposable elements (TEs) contribute to a large fraction of the expansion of many eukaryotic genomes due to the capability of TEs duplicating themselves through transposition. A first step to understanding the roles of TEs in a eukaryotic genome is to characterize the population-wide variation of TE insertions in the species. Here, we present a maximum-likelihood (ML) method for estimating allele frequencies and detecting selection on TE insertions in a diploid population, based on the genotypes at TE insertion sites detected in multiple individuals sampled from the population using paired-end (PE) sequencing reads. Tests of the method on simulated data show that it can accurately estimate the allele frequencies of TE insertions even when the PE sequencing is conducted at a relatively low coverage (=5X). The method can also detect TE insertions under strong selection, and the detection ability increases with sample size in a population, although a substantial fraction of actual TE insertions under selection may be undetected. Application of the ML method to genomic sequencing data collected from a natural Daphnia pulex population shows that, on the one hand, most (>90%) TE insertions present in the reference D. pulex genome are either fixed or nearly fixed (with allele frequencies >0.95); on the other hand, among the nonreference TE insertions (i.e., those detected in some individuals in the population but absent from the reference genome), the majority (>70%) are still at low frequencies (<0.1). Finally, we detected a substantial fraction (∼9%) of nonreference TE insertions under selection.

Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function

Thu, 02 Aug 2018 00:00:00 GMT

Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. The essential function of many proteins that fold into a specific structure is their ability to bind to a ligand, which can be assayed for thousands of mutated variants. However, binding assays do not distinguish whether mutations affect the stability of the binding interface or the overall fold. Here, we introduce a statistical method to infer a detailed energy landscape of how a protein folds and binds to a ligand by combining information from many mutated variants. We fit a thermodynamic model describing the bound, unbound, and unfolded states to high quality data of protein G domain B1 binding to IgG-Fc. We infer distinct folding and binding energies for each mutation providing a detailed view of how mutations affect binding and stability across the protein. We accurately infer the folding energy of each variant in physical units, validated by independent data, whereas previous high-throughput methods could only measure indirect changes in stability. While we assume an additive sequence–energy relationship, the binding fraction is epistatic due its nonlinear relation to energy. Despite having no epistasis in energy, our model explains much of the observed epistasis in binding fraction, with the remaining epistasis identifying conformationally dynamic regions.

Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It

Thu, 02 Aug 2018 00:00:00 GMT

The rate of recombination impacts on rates of protein evolution for at least two reasons: it affects the efficacy of selection due to linkage and influences sequence evolution through the process of GC-biased gene conversion (gBGC). We studied how recombination, via gBGC, affects inferences of selection in gene sequences using comparative genomic and population genomic data from the collared flycatcher (Ficedula albicollis). We separately analyzed different mutation categories (“strong”-to-“weak,” “weak-to-strong,” and GC-conservative changes) and found that gBGC impacts on the distribution of fitness effects of new mutations, and leads to that the rate of adaptive evolution and the proportion of adaptive mutations among nonsynonymous substitutions are underestimated by 22–33%. It also biases inferences of demographic history based on the site frequency spectrum. In light of this impact, we suggest that inferences of selection (and demography) in lineages with pronounced gBGC should be based on GC-conservative changes only. Doing so, we estimate that 10% of nonsynonymous mutations are effectively neutral and that 27% of nonsynonymous substitutions have been fixed by positive selection in the flycatcher lineage. We also find that gene expression level, sex-bias in expression, and the number of protein–protein interactions, but not Hill–Robertson interference (HRI), are strong determinants of selective constraint and rate of adaptation of collared flycatcher genes. This study therefore illustrates the importance of disentangling the effects of different evolutionary forces and genetic factors in interpretation of sequence data, and from that infer the role of natural selection in DNA sequence evolution.

Within-Gene Shine–Dalgarno Sequences Are Not Selected for Function

Wed, 01 Aug 2018 00:00:00 GMT

The Shine–Dalgarno (SD) sequence motif facilitates translation initiation and is frequently found upstream of bacterial start codons. However, thousands of instances of this motif occur throughout the middle of protein coding genes in a typical bacterial genome. Here, we use comparative evolutionary analysis to test whether SD sequences located within genes are functionally constrained. We measure the conservation of SD sequences across Enterobacteriales, and find that they are significantly less conserved than expected. Further, the strongest SD sequences are the least conserved whereas we find evidence of conservation for the weakest possible SD sequences given amino acid constraints. Our findings indicate that most SD sequences within genes are likely to be deleterious and removed via selection. To illustrate the origin of these deleterious costs, we show that ATG start codons are significantly depleted downstream of SD sequences within genes, highlighting the constraint that these sequences impose on the surrounding nucleotides to minimize the potential for erroneous translation initiation.

Evidence for a Unique DNA-Dependent RNA Polymerase in Cereal Crops

Tue, 24 Jul 2018 00:00:00 GMT

Gene duplication is an important driver for the evolution of new genes and protein functions. Duplication of DNA-dependent RNA polymerase (Pol) II subunits within plants led to the emergence of RNA Pol IV and V complexes, each of which possess unique functions necessary for RNA-directed DNA Methylation. Comprehensive identification of Pol V subunit orthologs across the monocot radiation revealed a duplication of the largest two subunits within the grasses (Poaceae), including critical cereal crops. These paralogous Pol subunits display sequence conservation within catalytic domains, but their carboxy terminal domains differ in length and character of the Ago-binding platform, suggesting unique functional interactions. Phylogenetic analysis of the catalytic region indicates positive selection on one paralog following duplication, consistent with retention via neofunctionalization. Positive selection on residue pairs that are predicted to interact between subunits suggests that paralogous subunits have evolved specific assembly partners. Additional Pol subunits as well as Pol-interacting proteins also possess grass-specific paralogs, supporting the hypothesis that a novel Pol complex with distinct function has evolved in the grass family, Poaceae.

Rapid Viral Symbiogenesis via Changes in Parasitoid Wasp Genome Architecture

Tue, 24 Jul 2018 00:00:00 GMT

Viral genome integration provides a complex route to biological innovation that has rarely but repeatedly occurred in one of the most diverse lineages of organisms on the planet, parasitoid wasps. We describe a novel endogenous virus in braconid wasps derived from pathogenic alphanudiviruses. Limited to a subset of the genus Fopius, this recent acquisition allows an unprecedented opportunity to examine early endogenization events. Massive amounts of virus-like particles (VLPs) are produced in wasp ovaries. Unlike most endogenous viruses of parasitoid wasps, the VLPs do not contain DNA, translating to major differences in parasitism-promoting strategies. Rapid changes include genomic rearrangement, loss of DNA processing proteins, and wasp control of viral gene expression. These events precede the full development of tissue-specific viral gene expression observed in older associations. These data indicate that viral endogenization can rapidly result in functional and evolutionary changes associated with genomic novelty and adaptation in parasitoids.

Species Tree Inference with BPP Using Genomic Sequences and the Multispecies Coalescent

Mon, 23 Jul 2018 00:00:00 GMT

The multispecies coalescent provides a natural framework for accommodating ancestral genetic polymorphism and coalescent processes that can cause different genomic regions to have different genealogical histories. The Bayesian program BPP includes a full-likelihood implementation of the multispecies coalescent, using transmodel Markov chain Monte Carlo to calculate the posterior probabilities of different species trees. BPP is suitable for analyzing multilocus sequence data sets and it accommodates the heterogeneity of gene trees (both the topology and branch lengths) among loci and gene tree uncertainties due to limited phylogenetic information at each locus. Here, we provide a practical guide to the use of BPP in species tree estimation. BPP is a command-line program that runs on linux, macosx, and windows. This protocol shows how to use both BPP 3.4 (http://abacus.gene.ucl.ac.uk/software/) and BPP 4.0 (https://github.com/bpp/).

Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex

Fri, 20 Jul 2018 00:00:00 GMT

Expression of transposable elements (TE) is transiently activated during human preimplantation embryogenesis in a developmental stage- and cell type-specific manner and TE-mediated epigenetic regulation is intrinsically wired in developmental genetic networks in human embryos and embryonic stem cells. However, there are no systematic studies devoted to a comprehensive analysis of the TE transcriptome in human adult organs and tissues, including human neural tissues. To investigate TE expression in the human Dorsolateral Prefrontal Cortex (DLPFC), we developed and validated a straightforward analytical approach to chart quantitative genome-wide expression profiles of all annotated TE loci based on unambiguous mapping of discrete TE-encoded transcripts using a de novo assembly strategy. To initially evaluate the potential regulatory impact of DLPFC-expressed TE, we adopted a comparative evolutionary genomics approach across humans, primates, and rodents to document conservation patterns, lineage-specificity, and colocalizations with transcription factor binding sites mapped within primate- and human-specific TE. We identified 654,665 transcripts expressed from 477,507 distinct loci of different TE classes and families, the majority of which appear to have originated from primate-specific sequences. We discovered 4,687 human-specific and transcriptionally active TEs in DLPFC, of which the prominent majority (80.2%) appears spliced. Our analyses revealed significant associations of DLPFC-expressed TE with primate- and human-specific transcription factor binding sites, suggesting potential cross-talks of concordant regulatory functions. We identified 1,689 TEs differentially expressed in the DLPFC of Schizophrenia patients, a majority of which is located within introns of 1,137 protein-coding genes. Our findings imply that identified DLPFC-expressed TEs may affect human brain structures and functions following different evolutionary trajectories. On one side, hundreds of thousands of TEs maintained a remarkably high conservation for ∼8 My of primates’ evolution, suggesting that they are likely conveying evolutionary-constrained primate-specific regulatory functions. In parallel, thousands of transcriptionally active human-specific TE loci emerged more recently, suggesting that they could be relevant for human-specific behavioral or cognitive functions.

Exon-Capture-Based Phylogeny and Diversification of the Venomous Gastropods (Neogastropoda, Conoidea)

Thu, 19 Jul 2018 00:00:00 GMT

Transcriptome-based exon capture methods provide an approach to recover several hundred markers from genomic DNA, allowing for robust phylogenetic estimation at deep timescales. We applied this method to a highly diverse group of venomous marine snails, Conoidea, for which published phylogenetic trees remain mostly unresolved for the deeper nodes. We targeted 850 protein coding genes (678,322 bp) in ca. 120 samples, spanning all (except one) known families of Conoidea and a broad selection of non-Conoidea neogastropods. The capture was successful for most samples, although capture efficiency decreased when DNA libraries were of insufficient quality and/or quantity (dried samples or low starting DNA concentration) and when targeting the most divergent lineages. An average of 75.4% of proteins was recovered, and the resulting tree, reconstructed using both supermatrix (IQ-tree) and supertree (Astral-II, combined with the Weighted Statistical Binning method) approaches, are almost fully supported. A reconstructed fossil-calibrated tree dates the origin of Conoidea to the Lower Cretaceous. We provide descriptions for two new families. The phylogeny revealed in this study provides a robust framework to reinterpret changes in Conoidea anatomy through time. Finally, we used the phylogeny to test the impact of the venom gland and radular type on diversification rates. Our analyses revealed that repeated losses of the venom gland had no effect on diversification rates, while families with a breadth of radula types showed increases in diversification rates, thus suggesting that trophic ecology may have an impact on the evolution of Conoidea.

Functional Shifts in Bat Dim-Light Visual Pigment Are Associated with Differing Echolocation Abilities and Reveal Molecular Adaptation to Photic-Limited Environments

Mon, 16 Jul 2018 00:00:00 GMT

Bats are excellent models for studying the molecular basis of sensory adaptation. In Chiroptera, a sensory trade-off has been proposed between the visual and auditory systems, though the extent of this association has yet to be fully examined. To investigate whether variation in visual performance is associated with echolocation, we experimentally assayed the dim-light visual pigment rhodopsin from bat species with differing echolocation abilities. While spectral tuning properties were similar among bats, we found that the rate of decay of their light-activated state was significantly slower in a nonecholocating bat relative to species that use distinct echolocation strategies, consistent with a sensory trade-off hypothesis. We also found that these rates of decay were remarkably slower compared with those of other mammals, likely indicating an adaptation to dim light. To examine whether functional changes in rhodopsin are associated with shifts in selection intensity upon bat Rh1 sequences, we implemented selection analyses using codon-based likelihood clade models. While no shifts in selection were identified in response to diverse echolocation abilities of bats, we detected a significant increase in the intensity of evolutionary constraint accompanying the diversification of Chiroptera. Taken together, this suggests that substitutions that modulate the stability of the light-activated rhodopsin state were likely maintained through intensified constraint after bats diversified, being finely tuned in response to novel sensory specializations. Our study demonstrates the power of combining experimental and computational approaches for investigating functional mechanisms underlying the evolution of complex sensory adaptations.

Evolution on the Biophysical Fitness Landscape of an RNA Virus

Thu, 28 Jun 2018 00:00:00 GMT

Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics that propagates millions of independent small viral subpopulations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction, an atypical case in evolution. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs between molecular traits of viral proteins shape viral evolution.

Duplication of hsp-110 Is Implicated in Differential Success of Globodera Species under Climate Change

Thu, 28 Jun 2018 00:00:00 GMT

Managing the emergence and spread of crop pests and pathogens is essential for global food security. Understanding how organisms have adapted to their native climate is key to predicting the impact of climate change. The potato cyst nematodes Globodera pallida and G. rostochiensis are economically important plant pathogens that cause yield losses of up to 50% in potato. The two species have different thermal optima that may relate to differences in the altitude of their regions of origin in the Andes. Here, we demonstrate that juveniles of G. pallida are less able to recover from heat stress than those of G. rostochiensis. Genome-wide analysis revealed that while both Globodera species respond to heat stress by induction of various protective heat-inducible genes, G. pallida experiences heat stress at lower temperatures. We use C. elegans as a model to demonstrate the dependence of the heat stress response on expression of Heat Shock Factor-1 (HSF-1). Moreover, we show that hsp-110 is induced by heat stress in G. rostochiensis, but not in the less thermotolerant G. pallida. Sequence analysis revealed that this gene and its promoter was duplicated in G. rostochiensis and acquired thermoregulatory properties. We show that hsp-110 is required for recovery from acute thermal stress in both C. elegans and in G. rostochiensis. Our findings point towards an underlying molecular mechanism that allows the differential expansion of one species relative to another closely related species under current climate change scenarios. Similar mechanisms may be true of other invertebrate species with pest status.

Specificity of the DNA Mismatch Repair System (MMR) and Mutagenesis Bias in Bacteria

Mon, 25 Jun 2018 00:00:00 GMT

The mutation rate of an organism is influenced by the interaction of evolutionary forces such as natural selection and genetic drift. However, the mutation spectrum (i.e., the frequency distribution of different types of mutations) can be heavily influenced by DNA repair. Using mutation-accumulation lines of the extremophile bacterium Deinococcus radiodurans ΔmutS1 and the model soil bacterium Pseudomonas fluorescens wild-type and MMR⁻ (Methyl-dependent Mismatch Repair-deficient) strains, we report the mutational features of these two important bacteria. We find that P. fluorescens has one of the highest MMR repair efficiencies among tested bacteria. We also discover that MMR of D. radiodurans preferentially repairs deletions, contrary to all other bacteria examined. We then, for the first time, quantify genome-wide efficiency and specificity of MMR in repairing different genomic regions and mutation types, by evaluating the P. fluorescens and D. radiodurans mutation data sets, along with previously reported ones of Bacillus subtilis subsp. subtilis, Escherichia coli, Vibrio cholerae, and V. fischeri. MMR in all six bacteria shares two general features: 1) repair efficiency is influenced by the neighboring base composition for both transitions and transversions, not limited to transversions as previously reported; and 2) MMR only recognizes indels <4 bp in length. This study demonstrates the power of mutation accumulation lines in quantifying DNA repair and mutagenesis patterns.

Recurrent Amplification of the Heterochromatin Protein 1 (HP1) Gene Family across Diptera

Tue, 19 Jun 2018 00:00:00 GMT

The heterochromatic genome compartment mediates strictly conserved cellular processes such as chromosome segregation, telomere integrity, and genome stability. Paradoxically, heterochromatic DNA sequence is wildly unconserved. Recent reports that many hybrid incompatibility genes encode heterochromatin proteins, together with the observation that interspecies hybrids suffer aberrant heterochromatin-dependent processes, suggest that heterochromatic DNA packaging requires species-specific innovations. Testing this model of coevolution between fast-evolving heterochromatic DNA and its packaging proteins begins with defining the latter. Here we describe many such candidates encoded by the Heterochromatin Protein 1 (HP1) gene family across Diptera, an insect Order that encompasses dramatic episodes of heterochromatic sequence turnover. Using BLAST, synteny analysis, and phylogenetic tree building across 64 Diptera genomes, we discovered a staggering 121 HP1 duplication events. In contrast, we observed virtually no gene duplication in gene families that share a common “chromodomain” with HP1s, including Polycomb and Su(var)3-9. The remarkably high number of Dipteran HP1 paralogs arises from distant clades undergoing convergent HP1 family amplifications. These independently derived, young HP1s span diverse ages, domain structures, and rates of molecular evolution, including episodes of positive selection. Moreover, independently derived HP1s exhibit convergent expression evolution. While ancient HP1 parent genes are transcribed ubiquitously, young HP1 paralogs are transcribed primarily in male germline tissue, a pattern typical of young genes. Pervasive gene youth, rapid evolution, and germline specialization implicate heterochromatin-encoded selfish elements driving recurrent HP1 gene family expansions. The 121 young genes offer valuable experimental traction for elucidating the germline processes shaped by Diptera’s many dramatic episodes of heterochromatin turnover.