Biology subjects

Thoma, J.

Publications and source records attributed to Thoma, J..

4 recordsLinked to original sources

bioRxiv2026

Evolutionary persistence of a highly prevalent multicopy mitochondrial-derived nuclear insertion (Mega-NUMT) in Neotropical Drosophila flies

Background: Although strict maternal transmission of mitochondria is a general feature of animals and humans for ensuring homogeneity in mitochondrial DNA (mtDNA) across generations, exceptions were reported in the recent past. For example, some extremely rare but spectacular cases of heteroplasmy and paternal transmission in humans have questioned the universal evolutionary principle. Hence, as an alternative, the Mega-NUMT concept was coined to explain this discovery and was thereafter partly proven to exist. This concept expands on the quite common transfer of mtDNA fragments to the nucleus (NUMTs) by considering the existence of multicopy mitochondrial nuclear insertions. Mega-NUMT reports are currently restricted to a few cases in animals, including humans. However, even in humans, their detailed genomic organization, natural prevalence, and potential biological functions remain unclear. Methodology/Principal Findings: Here, we discovered that up to 60 full-sized mitochondrial genomes are integrated into the nuclear genome of the neotropical fruit fly Drosophila paulistorum using long-read sequencing and confirmed their presence by in situ hybridization. The copies are organized in one cluster on chromosome 3, which we, due to its similarity with the Mega-NUMT concept, designated the Dpau Mega-NUMT. Contrary to the rarity in humans, this Mega-NUMT is found at high prevalence (40%) in both long-term laboratory lines and natural D. paulistorum populations of different semispecies. Additionally, the mitochondrial copies in the Mega-NUMT cluster are phylogenetically separated from the current mitotypes of D. paulistorum. Together, these observations suggest long-term maintenance of the Mega-NUMT in nature. Hence, we propose that the Dpau Mega-NUMT may have been transferred to the nuclear genome before D. paulistorum semispecies radiation and maintained at relatively high prevalence in nature by balancing selection due to yet undetermined functions. Conclusions/Significance: To our knowledge, this is the first verified existence and detailed dissection of a Mega-NUMT outside cats and humans. We show that Mega-NUMTs can be persistent in nature, even at high prevalence, potentially due to balancing selection. Our findings strengthen the importance of high-quality long-read sequencing technologies for deciphering complex repeat-rich genomic regions to deepen our understanding of the dynamics of genome evolution within genomic dark matter.

evolutionary biology↗

bioRxiv2022

Inherent dynamics of maltose binding protein (MBP) are immune to the native environment.

Biophysical characterizations of proteins typically rely on a reductionistic approach, studying proteins in a highly purified from and in absence of their natural cellular environment. Little is known about how the highly crowded conditions prevalent within living cells influence the dynamic structures proteins on the molecular level. To address this outstanding question, we characterize here the dynamic behavior of the periplasmic model protein MBP from Escherichia coli in situ, confined in the native lumen of bacterial outer membrane vesicles. To this end we determine the dynamics of side-chain methyl groups of MBP across several timescales and compare them to purified in vitro MBP. We find that the inherent dynamics of MBP are surprisingly insensitive to the native cellular environment and that the molecular motion of the protein is mainly impacted on a global level.

biophysics↗

bioRxiv2020

Persistence and invasiveness of high-level heteroplasmy through biparental transmission of a selfish mitochondrion in Drosophila.

Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre- and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name and {beta}. Identification and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an -like mitochondrial ancestor and indicate that both the and {beta} mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mitochondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.

evolutionary biology↗

bioRxiv2020

Structural basis of DegP-protease temperature-dependent activation

Protein quality control is an essential cellular function mainly executed by a vast array of different proteases and molecular chaperones. One of the bacterial HtrA (high temperature requirement A) protein family members, the homo-oligomeric DegP-protease, plays a crucial role in the Escherichia coli (E. coli) protein quality control machinery by removing unfolded proteins or preventing their aggregation and chaperoning them to their final folded state within the periplasm. DegP contains two regulatory PDZ domains, which play key roles in substrate recognition and in the transformation of DegP between inactive hexameric and proteolytic active cage-like structures. Here, we analyze the interaction and dynamics of the DegP PDZ-domains underlying this transformation by high-resolution NMR spectroscopy complemented with biochemical cleavage assays. We identify an interdomain molecular lock, which controls the interactions between the two PDZ domains, regulated by fine-tuned temperature-dependent protein dynamics, and which is potentially conserved in proteins harboring tandem PDZ domains.

biophysics↗