Project description:We have compared allelic and gene expression variation using individual-based RNA-seq data from four regional populations of the Glanville fritillary butterfly (Melitaea cinxia) in northern Europe. Two of the populations represent fragmented habitat and two continuous habitat. Based on sequence information, we constructed genealogy for four populations. Based on gene expression, we found 1841 genes to be differentially expressed between two different landscape types. Our results demonstrate genomic adaptations to living in fragmented landscapes, which are likely to be related to phenotypic life-history adaptations that have been documented for many species.
Project description:We have compared allelic and gene expression variation using individual-based RNA-seq data from four regional populations of the Glanville fritillary butterfly (Melitaea cinxia) in northern Europe. Two of the populations represent fragmented habitat and two continuous habitat. Based on sequence information, we constructed genealogy for four populations. Based on gene expression, we found 1841 genes to be differentially expressed between two different landscape types. Our results demonstrate genomic adaptations to living in fragmented landscapes, which are likely to be related to phenotypic life-history adaptations that have been documented for many species. RNA-seq from thorax, 174 individuals from four populations.
Project description:Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but it is not clear how they arise and propagate in the humans. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Close scrutiny revealed the signature of selection against non-synonymous variants in the protein-coding region, tRNA gene variants, and variants in specific regions of the non-coding D-loop. In isolated single PGCs we saw a profound reduction in the cellular mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules during early germline development. Single cell deep mtDNA sequencing showed rare variants reaching higher heteroplasmy levels in later PGCs, consistent with the observed genetic bottleneck, and predicting >80% levels within isolated organelles. Genome-wide RNA-seq showed a progressive upregulation of genes involving mtDNA replication and transcription, linked to a transition from glycolytic to oxidative metabolism. The metabolic shift exposes deleterious mutations to selection at the organellar level during early germ cell development. In this way, the genetic bottleneck prevents the relentless accumulation of mtDNA mutations in the human population predicted by Muller’s ratchet. Mutations escaping this mechanism will, however, show massive shifts in heteroplasmy levels within one human generation, explaining the extreme phenotypic variation seen in human pedigrees with inherited mtDNA disorders.
Project description:Most humans carry a mixed population of mitochondrial DNA (mtDNA heteroplasmy) affecting ~1-2% of molecules, but rapid percentage shifts occur over one generation leading to severe mitochondrial diseases. A decrease in the amount of mtDNA within the developing female germ line appears to play a role, but other sub-cellular mechanisms have been implicated. Establishing an in vitro model of early mammalian germ cell development from embryonic stem cells, here we show the reduction of mtDNA content is modulated by oxygen and reaches a nadir immediately before germ cell specification. The observed genetic bottleneck was accompanied by a decrease in mtDNA replicating foci and the segregation of heteroplasmy, which were both abolished at higher oxygen levels. Thus, differences in oxygen tension during early development can modulate mtDNA segregation, facilitating germ-line purification, and contribute to tissue-specific somatic mutation loads.