Browsing by Subject "recombination"

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  • Littrell, John; Tsaih, Shirng-Wern; Baud, Amelie; Rastas, Pasi; Solberg-Woods, Leah; Flister, Michael J. (2018)
    An accurate and high-resolution genetic map is critical for mapping complex traits, yet the resolution of the current rat genetic map is far lower than human and mouse, and has not been updated since the original Jensen-Seaman map in 2004. For the first time, we have refined the rat genetic map to sub-centimorgan (cM) resolution (
  • Fewer, David P.; Metsä-Ketelä, Mikko (2020)
    Abstract Microbes are talented chemists with the ability to generate tremendously complex and diverse natural products which harbor potent biological activities. Natural products are produced using sets of specialized biosynthetic enzymes encoded by secondary metabolism pathways. Here, we present a two-step evolutionary model to explain the diversification of biosynthetic pathways that account for the proliferation of these molecules. We argue that the appearance of natural product families has been a slow and infrequent process. The first step led to the original emergence of bioactive molecules and different classes of natural products. However, much of the chemical diversity observed today has resulted from the endless modification of the ancestral biosynthetic pathways. The second step rapidly modulates the pre-existing biological activities to increase their potency and to adapt to changing environmental conditions. We highlight the importance of enzyme promiscuity in this process, as it facilitates both the incorporation of horizontally transferred genes into secondary metabolic pathways and the functional differentiation of proteins to catalyze novel chemistry. We provide examples where single point mutations or recombination events have been sufficient for new enzymatic activities to emerge. A unique feature in the evolution of microbial secondary metabolism is that gene duplication is not essential but offers opportunities to synthesize more complex metabolites. Microbial natural products are highly important for the pharmaceutical industry due to their unique bioactivities. Therefore, understanding the natural mechanisms leading to the formation of diverse metabolic pathways is vital for future attempts to utilize synthetic biology for the generation of novel molecules.
  • Rastas, Pasi; Calboli, Federico C. F.; Guo, Baocheng; Shikano, Takahito; Merilä, Juha (2016)
    High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium, and chromosomal rearrangements across chromosomes, sexes, and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identity errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultradense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F-2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (similar to 6 markers/cM) linkage maps containing 18,691 and 20,054 single nucleotide polymorphisms. The two maps showed a high degree of synteny, but female maps were 1.5-2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (
  • Meric, Guillaume; Miragaia, Maria; de Been, Mark; Yahara, Koji; Pascoe, Ben; Mageiros, Leonardos; Mikhail, Jane; Harris, Llinos G.; Wilkinson, Thomas S.; Rolo, Joana; Lamble, Sarah; Bray, James E.; Jolley, Keith A.; Hanage, William P.; Bowden, Rory; Maiden, Martin C. J.; Mack, Dietrich; de Lencastre, Herminia; Feil, Edward J.; Corander, Jukka; Sheppard, Samuel K. (2015)
    The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species.
  • Seecharran, Tristan; Kalin-Manttari, Laura; Koskela, Katja; Nikkari, Simo; Dickins, Benjamin; Corander, Jukka; Skurnik, Mikael; McNally, Alan (2017)
    Yersinia pseudotuberculosis is a Gram-negative intestinal pathogen of humans and has been responsible for several nationwide gastrointestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic species of the genus Yersinia, Yersinia pestis and Yersinia enterocolitica allowing a high-resolution understanding of the ecology, evolution and dissemination of these pathogens. However, to date no purpose-designed large-scale global population genomic analysis of Y. pseudotuberculosis has been performed. Here we present analyses of the genomes of 134 strains of Y. pseudotuberculosis isolated from around the world, from multiple ecosystems since the 1960s. Our data display a phylogeographic split within the population, with an Asian ancestry and subsequent dispersal of successful clonal lineages into Europe and the rest of the world. These lineages can be differentiated by CRISPR cluster arrays, and we show that the lineages are limited with respect to inter-lineage genetic exchange. This restriction of genetic exchange maintains the discrete lineage structure in the population despite co-existence of lineages for thousands of years in multiple countries. Our data highlights how CRISPR can be informative of the evolutionary trajectory of bacterial lineages, and merits further study across bacteria.
  • Ali, Akhtar; Gaur, Rajarshi Kumar; Wang, Xifeng; Cheng, Xiaofei; Mäkinen, Kristiina (2021)
  • Yang, Xiaochang (Helsingin yliopisto, 2019)
    Campylobacter jejuni is one of the leading causes of human gastroenteritis. Globally, there has been an increasing trend in the incidence of campylobacteriosis. In the European Union, about 200,000 cases of campylobacteriosis are reported annually. C. jejuni 4031 was isolated from a water outbreak in Finland. This strain belongs to the ST-45 clonal complex. According to a previous study, this population has been stable over time and space and has showed low levels of genomic diversity compared with other populations. Therefore, it is meaningful to investigate the evolutionary mechanisms and ecological conditions behind these clones. The aim of this study was to investigate the evolution of C. jejuni 4031 by whole genome sequencing and bioinformatics tools, characterizing the rate and molecular spectrum of spontaneous mutation in these clones. In addition, the transformation pattern of C. jejuni 4031 was to be studied. This study composed of three independent experiments: mutation accumulation experiment, fluctuation analysis, and transformation cycle experiment, to investigate mutation and recombination events, respectively. The C. jejuni 4031 grown for 220 generations by single colony passaging method in NB2 agar plate and thereafter named C. jejuni 4031x12 was used as starting material for the studies. In total of 76 genomes from both mutation accumulation experiments and transformation cycle experiments, were subject to SNP calling. Results showed that C. jejuni 4031x12 could accumulate spontaneous mutations at a relatively low rate (4.1x10-10 mutation per generation per nucleotide) than conventional estimates, with mutational bias towards G:C>A:T transitions and coding regions. The fluctuation analysis proves that C. jejuni 4031x12 could obtain antibiotic resistance via transformation. However, no recombination events were observed from SNP results. In conclusion, C. jejuni 4031 has evolved at a much lower rate compared with prior knowledge. Results from fluctuation analysis and transformation cycle experiment suggest that there are no essential recombination barriers between C. jejuni 4031 and C. jejuni NCTC11168 but transformants may not have a competitive advantage over their non-transformed counterparts.
  • Murray, Susan; Pascoe, Ben; Meric, Guillaume; Mageiros, Leonardos; Yahara, Koji; Hitchings, Matthew D.; Friedmann, Yasmin; Wilkinson, Thomas S.; Gormley, Fraser J.; Mack, Dietrich; Bray, James E.; Lamble, Sarah; Bowden, Rory; Jolley, Keith A.; Maiden, Martin C. J.; Wendlandt, Sarah; Schwarz, Stefan; Corander, Jukka; Fitzgerald, J. Ross; Sheppard, Samuel K. (2017)
    Staphylococcus aureus are globally disseminated among farmed chickens causing skeletal muscle infections, dermatitis, and septicaemia. The emergence of poultry-associated lineages has involved zoonotic transmission from humans to chickens but questions remain about the specific adaptations that promote proliferation of chicken pathogens. We characterized genetic variation in a population of genome-sequenced S. aureus isolates of poultry and humanorigin. Genealogical analysis identified a dominant poultry-associated sequence cluster within the CC5 clonal complex. Poultry and human CC5 isolates were significantly distinct from each other and more recombination events were detected in the poultry isolates. We identified 44 recombination events in 33 genes along the branch extending to the poultry-specific CC5 cluster, and 47 genes were found more often in CC5 poultry isolates compared with those from humans. Many of these gene sequences were common in chicken isolates from other clonal complexes suggesting horizontal gene transfer among poultry associated lineages. Consistent with functional predictions for putative poultry-associated genes, poultry isolates showed enhanced growth at 42 degrees C and greater erythrocyte lysis on chicken blood agar in comparison with human isolates. By combining phenotype information with evolutionary analyses of staphylococcal genomes, we provide evidence of adaptation, following a human-to-poultry host transition. This has important implications for the emergence and dissemination of new pathogenic clones associated with modern agriculture.