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Matt Berriman

Publications and source records attributed to Matt Berriman.

7 recordsLinked to original sources

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.

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Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii.

Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T.gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T.gondii. The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at approximately 300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of approximately 592 cM and an average map unit of approximately 104 kb/cM. Analysis of the genetic parameters in T.gondii revealed a high frequency of closely adjacent, apparent double crossover events that may represent gene conversions. In addition, we detected large regions of genetic homogeneity among the archetypal clonal lineages, reflecting the relatively few genetic outbreeding events that have occurred since their recent origin. Despite these unusual features, linkage analysis proved to be effective in mapping the loci determining several drug resistances. The resulting genome map provides a framework for analysis of complex traits such as virulence and transmission, and for comparative population genetic studies.

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Evolution of noncoding and silent coding sites in the Plasmodium falciparum and Plasmodium reichenowi genomes.

We compared levels of sequence divergence between fourfold synonymous coding sites and noncoding sites from the intergenic and intronic regions of the Plasmodium falciparum and Plasmodium reichenowi genomes. We observed significant differences in the level of divergence between these classes of silent sites. Fourfold synonymous coding sites exhibited the highest level of sequence divergence, followed by introns, and then intergenic sequences. This pattern of relative divergence rates has been observed in primate genomes but was unexpected in Plasmodium due to a paucity of variation at silent sites in P. falciparum and the corollary hypothesis that silent sites in this genome may be subject to atypical selective constraints. Exclusion of hypermutable CpG dinucleotides reduces the divergence level of synonymous coding sites to that of intergenic sites but does not diminish the significantly higher divergence level of introns relative to intergenic sites. A greater than expected incidence of CpG dinucleotides in intergenic regions less than 500 bp from genes may indicate selective maintenance of regulatory motifs containing CpGs. Divergence rates of different classes of silent sites in these Plasmodium genomes are determined by a combination of mutational and selective pressures.

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The genome of the protist parasite Entamoeba histolytica.

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

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A case for a Glossina genome project.

Given the medical and agricultural significance of Glossina, knowledge of the genomic aspects of the vector and vector-pathogen interactions are a high priority. In preparation for a full genome sequence initiative, an extensive set of expressed sequence tags (ESTs) has been generated from tissue-specific normalized libraries. In addition, bacterial artificial chromosome (BAC) libraries are being constructed, and information on the genome structure and size from different species has been obtained. An international consortium is now in place to further efforts to lead to a full genome project.

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Viewing and annotating sequence data with Artemis.

Artemis is a widely used software tool for annotating and viewing sequence data. No database is required to use Artemis. Instead, individual sequence data files can be analysed with little or no formatting, making it particularly suited to the study of small genomes and chromosomes, and straightforward for a novice user to get started. Since its release in 1999, Artemis has been used to annotate a diverse collection of prokaryotic and eukaryotic genomes, ranging from Streptomyces coelicolor to, more recently, a large proportion of the Plasmodium falciparum genome. Artemis allows annotated genomes to be easily browsed and makes it simple to add useful biological information to raw sequence data. This paper gives an overview of some of the features of Artemis and includes how it facilitates manual gene prediction and can provide an overview of entire chromosomes or small compact genomes--useful for uncovering unusual features such as pathogenicity islands.

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