Biology subjects

Pienaar, J.

Publications and source records attributed to Pienaar, J..

3 recordsLinked to original sources

bioRxiv2025

Co-mutation based genetic networks to infer temporal mutation dynamics in ancient human mitochondrial genomes

The evolution of modern humans is as fascinating as it is complicated. Various environmental and socio-political factors have played a significant role in shaping different migratory paths and lifestyles in ancient times and the establishment of current sub-populations around the globe. These factors have impacted the molecular evolution of mitochondrial DNA (mtDNA). To account for the role of genetic background and variable sites in shaping the migratory and evolutionary paths, we analyzed the ancient mtDNA as spatiotemporal co-mutation networks. Haplogroup-based analysis of the variable sites suggests a transition from hunter-gatherer to agrarian lifestyle during the Copper-Bronze transition period. Furthermore, the genetic interaction networks showed that COX and CYB genes behaved diversely with time and that there is an interplay of the genetic interactions with NADH Dehydrogenase genes specific to each age. We performed a phylogeny (tree) based gene network analysis and examined polymorphism to divergence ratios to complement the co-mutation networks. The tree-based gene networks exhibit similar topology with reduced co-mutation among the genes. The more traditional polymorphism/divergence analysis indicated that the CYB gene has been under long-term purifying selection. In contrast, other genes (ATP6, COX, NADH hydrogenases) have undergone episodes of purifying selection corresponding to different ages. We believe this network-based exploratory study provides insights into early lifestyle transitions and haplogroup establishment of the current human population.

evolutionary biology↗

bioRxiv2022

Genome size changes by duplication, insertion and divergence in Caenorhabditis worms

Genome size has been measurable since the 1940s but we still do not understand the basis of genome size variation. Caenorhabditis nematodes show strong conservation of chromosome number but vary in genome size between closely related species. Androdioecy, where populations are composed of males and self-fertile hermaphrodites, has evolved from outcrossing, female-male dioecy, three times in this group. Androdioecious genomes are 10-30% smaller than dioecious species but large phylogenetic distances and rapid protein evolution have made it difficult to pinpoint the basis of these changes. Here, we analyze the genome sequences of Caenorhabditis and and test three hypotheses explaining genome evolution: 1) genomes evolve through deletions and genome shrinkage in androdioecious species; 2) genome size is determined by transposable element (TE) expansion and DNA loss through large deletions (the accordion model); and 3) TE dynamics differ in androdioecious and dioecious species. We find no evidence for these hypotheses in Caenorhabditis. Across both short and long evolutionary distances Caenorhabditis genomes evolve through small structural variant (SV) mutations including frequent duplications and insertions, predominantly in genic regions. Caenorhabditis have rapid rates of gene family expansion and contraction and we identify 71 protein families with significant, parallel decreases across self-fertile Caenorhabditis. These include genes involved in the sensory system, regulatory proteins and membrane-associated immune responses, reflecting the shifting selection pressures that result from self-fertility. Our results suggest that the rules governing genome evolution differ between organisms based on ecology, life style and reproductive system.

evolutionary biology↗

bioRxiv2021

Neurovascular unit alterations in the growth restricted newborn are improved following ibuprofen treatment

Fetal brain development is particularly vulnerable to the effects of fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant. Adverse outcomes range from behavioural and learning disorders through to cerebral palsy. Unfortunately, no treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, a non-steroidal anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. We used a preclinical piglet model of growth restriction in which FGR occurs spontaneously. Newborn FGR (birthweight <10th centile) and normally grown piglets were collected on day of birth and oral ibuprofen was administered daily for 3 days (20mg/kg/day, day 1 and 10mg/kg/day days 2 and 3). FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident in the microvasculature where leakage was present, suggestive of structural deficits to the NVU. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen treatment also attenuated albumin and IgG leakage. There were no alterations to angiogenesis, or blood vessel proliferation in treated-FGR piglets. These findings suggest postnatal administration of ibuprofen on day of birth modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.

neuroscience↗