Inference of recombination maps from a single pair of genomes and its application to archaic samples

ABSTRACTUnderstanding the causes and consequences of recombination rate evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Since statistical inference of recombination maps typically depends on large samples, reaching out studies to non-model organisms requires alternative tools. Here we extend the sequentially Markovian coalescent model to jointly infer demography and the variation in recombination along a pair of genomes. Using extensive simulations and sequence data from humans, fruit-flies and a fungal pathogen, we demonstrate that iSMC accurately infers recombination maps under a wide range of scenarios – remarkably, even from a single pair of unphased genomes. We exploit this possibility and reconstruct the recombination maps of archaic hominids. We report that the evolution of the recombination landscape follows the established phylogeny of Neandertals, Denisovans and modern human populations, as expected if the genomic distribution of crossovers in hominids is largely neutral.

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mtDNAcombine: tools to combine sequences from multiple studies

BMC Bioinformatics ◽

10.1186/s12859-021-04048-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eleanor F. Miller ◽

Andrea Manica

Keyword(s):

Sequence Data ◽

Data Extraction ◽

Bayesian Skyline Plot ◽

Model Organisms ◽

Data Sets ◽

Data Handling ◽

Online Database ◽

Genetic Studies ◽

Wide Range ◽

Existing Data

Abstract Background Today an unprecedented amount of genetic sequence data is stored in publicly available repositories. For decades now, mitochondrial DNA (mtDNA) has been the workhorse of genetic studies, and as a result, there is a large volume of mtDNA data available in these repositories for a wide range of species. Indeed, whilst whole genome sequencing is an exciting prospect for the future, for most non-model organisms’ classical markers such as mtDNA remain widely used. By compiling existing data from multiple original studies, it is possible to build powerful new datasets capable of exploring many questions in ecology, evolution and conservation biology. One key question that these data can help inform is what happened in a species’ demographic past. However, compiling data in this manner is not trivial, there are many complexities associated with data extraction, data quality and data handling. Results Here we present the mtDNAcombine package, a collection of tools developed to manage some of the major decisions associated with handling multi-study sequence data with a particular focus on preparing sequence data for Bayesian skyline plot demographic reconstructions. Conclusions There is now more genetic information available than ever before and large meta-data sets offer great opportunities to explore new and exciting avenues of research. However, compiling multi-study datasets still remains a technically challenging prospect. The mtDNAcombine package provides a pipeline to streamline the process of downloading, curating, and analysing sequence data, guiding the process of compiling data sets from the online database GenBank.

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Glutton: large-scale integration of non-model organism transcriptome data for comparative analysis

10.1101/077511 ◽

2016 ◽

Cited By ~ 2

Author(s):

Alan Medlar ◽

Laura Laakso ◽

Andreia Miraldo ◽

Ari Löytynoja

Keyword(s):

Comparative Analysis ◽

Large Scale ◽

De Novo ◽

Sequence Data ◽

Model Organism ◽

Model Organisms ◽

Rna Seq ◽

Reference Species ◽

Wide Range ◽

The Impact

AbstractHigh-throughput RNA-seq data has become ubiquitous in the study of non-model organisms, but its use in comparative analysis remains a challenge. Without a reference genome for mapping, sequence data has to be de novo assembled, producing large numbers of short, highly redundant contigs. Preparing these assemblies for comparative analyses requires the removal of redundant isoforms, assignment of orthologs and converting fragmented transcripts into gene alignments. In this article we present Glutton, a novel tool to process transcriptome assemblies for downstream evolutionary analyses. Glutton takes as input a set of fragmented, possibly erroneous transcriptome assemblies. Utilising phylogeny-aware alignment and reference data from a closely related species, it reconstructs one transcript per gene, finds orthologous sequences and produces accurate multiple alignments of coding sequences. We present a comprehensive analysis of Glutton’s performance across a wide range of divergence times between study and reference species. We demonstrate the impact choice of assembler has on both the number of alignments and the correctness of ortholog assignment and show substantial improvements over heuristic methods, without sacrificing correctness. Finally, using inference of Darwinian selection as an example of downstream analysis, we show that Glutton-processed RNA-seq data give results comparable to those obtained from full length gene sequences even with distantly related reference species. Glutton is available from http://wasabiapp.org/software/glutton/ and is licensed under the GPLv3.

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Limits of long-term selection against Neandertal introgression

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814338116 ◽

2019 ◽

Vol 116 (5) ◽

pp. 1639-1644 ◽

Cited By ~ 48

Author(s):

Martin Petr ◽

Svante Pääbo ◽

Janet Kelso ◽

Benjamin Vernot

Keyword(s):

Negative Selection ◽

Modern Human ◽

Model Parameters ◽

Human Populations ◽

Modern Humans ◽

High Coverage ◽

Protein Coding ◽

The Past ◽

Wide Range

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.

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mtDNAcombine: tools to combine sequences from multiple studies

10.1101/2020.03.31.017806 ◽

2020 ◽

Author(s):

Eleanor F. Miller ◽

Andrea Manica

Keyword(s):

Conservation Biology ◽

Sequence Data ◽

Data Extraction ◽

Bayesian Skyline Plot ◽

Model Organisms ◽

Data Handling ◽

Genetic Studies ◽

Genetic Sequence ◽

Wide Range ◽

Existing Data

AbstractToday an unprecedented amount of genetic sequence data is stored in publicly available repositories. For decades now, mitochondrial DNA (mtDNA) has been the workhorse of genetic studies, and as a result, there is a large volume of mtDNA data available in these repositories for a wide range of species. Indeed, whilst whole genome sequencing is an exciting prospect for the future, for most non-model organisms’ classical markers such as mtDNA remain widely used. By compiling existing data from multiple original studies, it is possible to build powerful new datasets capable of exploring many questions in ecology, evolution and conservation biology. One key question that these data can help inform is what happened in a species’ demographic past. However, compiling data in this manner is not trivial, there are many complexities associated with data extraction, data quality and data handling. Here we present the mtDNAcombine package, a collection of tools developed to manage some of the major decisions associated with handling multi-study sequence data with a particular focus on preparing mtDNA data for Bayesian Skyline Plot demographic reconstructions.

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Reconstructing the past

Evolutionary Genetics ◽

10.1093/oso/9780198830917.003.0009 ◽

2019 ◽

pp. 214-249

Author(s):

Glenn-Peter Sætre ◽

Mark Ravinet

Keyword(s):

Phylogenetic Trees ◽

Evolutionary History ◽

Sequence Data ◽

Modern Human ◽

Evolutionary Relationships ◽

Human Populations ◽

Gene Trees ◽

Exciting Field ◽

History Of ◽

Life On Earth

How can genetics and genomics be used to understand the evolutionary history of organisms? This chapter focuses on such methods. First, the field of phylogenetics is introduced, as a way to visualize and quantify the evolutionary relationships among species. The chapter outlines how we go from aligning DNA sequence data to building gene trees and we argue that “tree-thinking” is fundamentally important for understanding evolution. The chapter also goes beyond phylogenetic trees to focus on phylogeography, i.e. the understanding of evolutionary relationships in a spatial context. More recently, the explosion of genomic data from ancient and modern human populations has made this an extremely exciting field which is transforming our understanding of our own evolutionary history. Before that, though, the chapter reviews how modern phylogenetics has arisen from historical efforts to classify life on Earth.

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Detecting Ancient Admixture in Humans Using Sequence Polymorphism Data

Genetics ◽

10.1093/genetics/154.3.1271 ◽

2000 ◽

Vol 154 (3) ◽

pp. 1271-1279 ◽

Cited By ~ 1

Author(s):

Jeffrey D Wall

Keyword(s):

Human Evolution ◽

Sequence Data ◽

Modern Human ◽

Sequence Polymorphism ◽

Parameter Estimates ◽

Human Populations ◽

Ancient Population ◽

Single Origin ◽

Polymorphism Data ◽

Nuclear Loci

Abstract A debate of long-standing interest in human evolution centers around whether archaic human populations (such as the Neanderthals) have contributed to the modern gene pool. A model of ancient population structure with recent mixing is introduced, and it is determined how much information (i.e., sequence data from how many unlinked nuclear loci) would be necessary to distinguish between different demographic scenarios. It is found that ~50–100 loci are necessary if plausible parameter estimates are used. There are not enough data available at the present to support either the “single origin” or the “multiregional” model of modern human evolution. However, this information should be available in a few years.

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An In Vitro Cell Culture Model for Pyoverdine-Mediated Virulence

Pathogens ◽

10.3390/pathogens10010009 ◽

2020 ◽

Vol 10 (1) ◽

pp. 9

Author(s):

Donghoon Kang ◽

Natalia V. Kirienko

Keyword(s):

Cell Culture ◽

Virulence Factors ◽

Model Organisms ◽

Cell Culture Model ◽

Chronic Infections ◽

In Vitro Cell Culture ◽

Mitochondrial Homeostasis ◽

Culture Model ◽

Wide Range

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.

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Sequence data from isolated lichen-associated melanized fungi enhance delimitation of two new lineages within Chaetothyriomycetidae

Mycological Progress ◽

10.1007/s11557-021-01706-8 ◽

2021 ◽

Vol 20 (7) ◽

pp. 911-927

Author(s):

Lucia Muggia ◽

Yu Quan ◽

Cécile Gueidan ◽

Abdullah M. S. Al-Hatmi ◽

Martin Grube ◽

...

Keyword(s):

Sequence Data ◽

Single Species ◽

Sister Group ◽

Asexual Propagation ◽

Dna Sequence Data ◽

Wide Range ◽

The Family ◽

Rock Inhabiting Fungi ◽

Stable Habitat

AbstractLichen thalli provide a long-lived and stable habitat for colonization by a wide range of microorganisms. Increased interest in these lichen-associated microbial communities has revealed an impressive diversity of fungi, including several novel lineages which still await formal taxonomic recognition. Among these, members of the Eurotiomycetes and Dothideomycetes usually occur asymptomatically in the lichen thalli, even if they share ancestry with fungi that may be parasitic on their host. Mycelia of the isolates are characterized by melanized cell walls and the fungi display exclusively asexual propagation. Their taxonomic placement requires, therefore, the use of DNA sequence data. Here, we consider recently published sequence data from lichen-associated fungi and characterize and formally describe two new, individually monophyletic lineages at family, genus, and species levels. The Pleostigmataceae fam. nov. and Melanina gen. nov. both comprise rock-inhabiting fungi that associate with epilithic, crust-forming lichens in subalpine habitats. The phylogenetic placement and the monophyly of Pleostigmataceae lack statistical support, but the family was resolved as sister to the order Verrucariales. This family comprises the species Pleostigma alpinum sp. nov., P. frigidum sp. nov., P. jungermannicola, and P. lichenophilum sp. nov. The placement of the genus Melanina is supported as a lineage within the Chaetothyriales. To date, this genus comprises the single species M. gunde-cimermaniae sp. nov. and forms a sister group to a large lineage including Herpotrichiellaceae, Chaetothyriaceae, Cyphellophoraceae, and Trichomeriaceae. The new phylogenetic analysis of the subclass Chaetothyiomycetidae provides new insight into genus and family level delimitation and classification of this ecologically diverse group of fungi.

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Insights into mammalian biology from the wild house mouse Mus musculus

eLife ◽

10.7554/elife.05959 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 45

Author(s):

Megan Phifer-Rixey ◽

Michael W Nachman

Keyword(s):

House Mouse ◽

Mus Musculus ◽

Genetic Model ◽

Inbred Strains ◽

Mendelian Inheritance ◽

Model Organisms ◽

House Mice ◽

Small Subset ◽

Wild Mice ◽

Wide Range

The house mouse, Mus musculus, was established in the early 1900s as one of the first genetic model organisms owing to its short generation time, comparatively large litters, ease of husbandry, and visible phenotypic variants. For these reasons and because they are mammals, house mice are well suited to serve as models for human phenotypes and disease. House mice in the wild consist of at least three distinct subspecies and harbor extensive genetic and phenotypic variation both within and between these subspecies. Wild mice have been used to study a wide range of biological processes, including immunity, cancer, male sterility, adaptive evolution, and non-Mendelian inheritance. Despite the extensive variation that exists among wild mice, classical laboratory strains are derived from a limited set of founders and thus contain only a small subset of this variation. Continued efforts to study wild house mice and to create new inbred strains from wild populations have the potential to strengthen house mice as a model system.

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