bioRxiv Science⌕ Search

Biology subjects

Sidhu, K.

Publications and source records attributed to Sidhu, K..

3 recordsLinked to original sources

Genome-wide association for loci influencing thermal performance curves in Neurospora crassa

Temperature poses a unique challenge to ectothermic species, as it affects all biochemical reactions in the cell and causes physiological stress. The effect of temperature on an organism can be described by a thermal performance curve (TPC), which displays organismal performance, such as growth rate, as a function of temperature. Previous studies on thermal performance have revealed different amounts of genetic variation and trade-offs in TPC shape and position within species and populations. However, very little is known about the genetic architecture of TPCs on the level of individual loci and alleles. We asked what is the identity of loci contributing to genetic variation in TPCs, and do the alleles exhibit trade-offs or thermodynamic scaling across the temperature range? We used genome-wide association mapping to find loci influencing growth rate at different temperatures and TPC traits in the filamentous fungus Neurospora crassa. We also evaluated the directions and magnitudes of allelic effects to investigate possible trade-offs. We observed both unique associations at specific temperatures, as some loci affected growth rate only at low, intermediate, or high temperatures, and associations that were shared across multiple temperatures. However, only weak evidence of trade-offs was detected, indicating that the evolution of TPCs in N. crassa is not constrained by allelic effects in opposite directions at hot and cold temperatures. Our findings indicate that trade-offs contribute little to variation in TPCs.

genetics↗

Alzheimer's disease induced neurons bearing PSEN1 mutations exhibit reduced excitability

Alzheimers disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in PSEN1 (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD progression, the link between PSEN1 mutations and neuronal excitability remains to be fully elucidated. This study examined induced pluripotent stem cell (iPSC)-derived NGN2 induced neurons (iNs) from fAD patients with PSEN1 mutations S290C or A246E, alongside CRISPR-corrected isogenic cell lines, to investigate early changes in excitability. Electrophysiological profiling revealed reduced excitability in both PSEN1 mutant iNs compared to their isogenic controls. Neurons bearing S290C and A246E mutations exhibited divergent passive membrane properties compared to isogenic controls, suggesting distinct effects of PSEN1 mutations on neuronal excitability. Additionally, both PSEN1 backgrounds exhibited higher current density of voltage-gated potassium (Kv) channels relative to their isogenic iNs, while displaying comparable voltage-gated sodium (Nav) channel current density. This suggests that the Nav/Kv imbalance contributes to impaired neuronal firing in fAD iNs. Deciphering these early cellular and molecular changes in AD is crucial for understanding the disease pathogenesis.

cell biology↗

Quantitative genetics of temperature performance curves of Neurospora crassa

Earths temperature is increasing due to anthropogenic CO2 emissions; and organisms need either to adapt to higher temperatures, migrate into colder areas, or face extinction. Temperature affects nearly all aspects of an organisms physiology via its influence on metabolic rate and protein structure, therefore genetic adaptation to increased temperature may be much harder to achieve compared to other abiotic stresses. There is still much to be learned about the evolutionary potential for adaptation to higher temperatures, therefore we studied the quantitative genetics of growth rates in different temperatures that make up the thermal performance curve of the fungal model system Neurospora crassa. We studied the amount of genetic variation for thermal performance curves and examined possible genetic constraints by estimating the G-matrix. We observed a substantial amount of genetic variation for growth in different temperatures, and most genetic variation was for performance curve elevation. Contrary to common theoretical assumptions, we did not find strong evidence for genetic trade-offs for growth between hotter and colder temperatures. We also simulated short term evolution of thermal performance curves of N. crassa, and suggest that they can have versatile responses to selection.

evolutionary biology↗