Biology subjects

Wiehe, T.

Publications and source records attributed to Wiehe, T..

4 recordsLinked to original sources

bioRxiv2018

Interdependence of linkage disequilibrium, chromatin architecture and compositional genome organization of mammals

Recent investigation established a link between DNA sequences and chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse the relationship between chromatin architecture and recombination landscapes of human and mouse. The results revealed that: (1) Blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhood; (2) double strand break (DSB) and recombination frequencies increase in GC-rich TADs, whereas recombination cold spots are typical of LADs; (3) binding and loading of proteins which are critical for DSB and meiotic recombination (Spo11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated to compositional and epigenetic features (genomic code) that are similar to those guiding the architecture of chromosomes in the interphase nucleus of pre-leptotene spermatocytes.

genomics↗

bioRxiv2018

Topological linkage disequilibrium calculated from coalescent genealogies

We revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure of LD. We call this topological LD (tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventional LD. Furthermore, tLD has a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventional LD. We conclude with a practical application to the LCT region in human populations.

evolutionary biology↗

bioRxiv2017

Signatures of the evolution of parthenogenesis and cryptobiosis in the genomes of panagrolaimid nematodes

Most animal species reproduce sexually, but parthenogenesis, asexual reproduction of various forms, has arisen repeatedly. Parthenogenetic lineages are usually short lived in evolution; though in some environments parthenogenesis may be advantageous, avoiding the cost of sex. Panagrolaimus nematodes have colonised environments ranging from arid deserts to arctic and antarctic biomes. Many are parthenogenetic, and most have cryptobiotic abilities, being able to survive repeated complete desiccation and freezing. It is not clear which genomic and molecular mechanisms led to the successful establishment of parthenogenesis and the evolution of cryptobiosis in animals in general. At the same time, model systems to study these traits in the laboratory are missing.\n\nWe compared the genomes and transcriptomes of parthenogenetic and sexual Panagrolaimus able to survive crybtobiosis, as well as a non-cryptobiotic Propanogrolaimus species, to identify systems that contribute to these striking abilities. The parthenogens are most probably tripoids originating from hybridisation (allopolyploids). We identified genomic singularities like expansion of gene families, and selection on genes that could be linked to the adaptation to cryptobiosis. All Panagrolaimus have acquired genes through horizontal transfer, some of which are likely to contribute to cryptobiosis. Many genes acting in C. elegans reproduction and development were absent in distant nematode species (including the Panagrolaimids), suggesting molecular pathways cannot directly be transferred from the model system.\n\nThe easily cultured Panagrolaimus nematodes offer a system to study developmental diversity in Nematoda, the molecular evolution of parthenogens, the effects of triploidy on genomes stability, and the origin and biology of cryptobiosis.

evolutionary biology↗

bioRxiv2017

The expected neutral frequency spectrum of linked sites

We introduce the conditional Site Frequency Spectrum (SFS) for a genomic region linked to a focal mutation of known frequency. An exact expression for its expected value is provided for the neutral model without recombination. Its relation with the expected SFS for two sites, 2-SFS, is discussed. These spectra derive from the coalescent approach of Fu (1995) for finite samples, which is reviewed. Remarkably simple expressions are obtained for the linked SFS of a large population, which are also solutions of the multiallelic Kolmogorov equations. These formulae are the immediate extensions of the well known single site{theta} /f neutral SFS. Besides the general interest in these spectra, they relate to relevant biological cases, such as structural variants and introgressions. As an application, a recipe to adapt Tajimas D and other SFS-based neutrality tests to a non-recombining region containing a neutral marker is presented.

genetics↗