Biomedical subjects

Dan Liang

Publications and source records attributed to Dan Liang.

3 recordsLinked to original sources

PubMed2026

Disruption of mitonuclear coadaptation and compensatory evolution after an extreme dietary shift in carnivorous butterflies.

Mitochondrial function depends on tight coordination between mitochondrial and nuclear genomes, which requires long-term coevolution to maintain mitonuclear coadaptation. While mitonuclear incompatibility is typically studied in the context of hybridization, other evolutionary scenarios that may disrupt coadaptation between the two genomes remain less explored. Here, we propose that extreme ecological niche shifts may disrupt mitonuclear coadaptation, which we test in carnivorous Miletinae butterflies with an extreme dietary transition. By generating high-quality genome assemblies, we found that Miletinae exhibit extensive chromosomal rearrangements. Comparative phylogenomic analyses revealed a striking asymmetric mitonuclear evolutionary response: Miletinae exhibit elevated mitochondrial nucleotide substitution rates compared to phytophagous relatives, whereas nuclear rates remain stable. This shift reverses the typical lepidopteran pattern where nuclear rates exceed mitochondrial rates. Interestingly, this mitochondrial acceleration is driven primarily by relaxed purifying selection rather than positive selection. To sustain mitochondrial function, the nuclear genome of Miletinae underwent pervasive, multilayered compensatory evolution. We detected strong signatures of positive selection and accelerated evolution in nuclear genes directly interacting with mitochondrial components across oxidative phosphorylation (OXPHOS) complexes, the mitochondrial translation, and replication and transcription machinery. Furthermore, this nuclear compensatory response extends to systems governing mitochondrial homeostasis, including protein quality control and RNA degradation and stabilization. Our results support a model in which extreme ecological transitions can disrupt ancestral mitonuclear coadaptation and promote the emergence of a new coadapted state through systemic nuclear compensation. This study broadens the conceptual framework of mitonuclear coevolution and highlights its role in facilitating evolutionary persistence after major ecological shifts.

Animals↗

PubMed2025

Human-specific features of the cerebellum and ZP2-regulated synapse development.

Understanding the unique features of the human brain compared to non-human primates has long intrigued humankind. The cerebellum refines motor coordination and cognitive functions, contributing to the evolutionary development of human adaptability and dexterity. To identify shared and divergent features across primates, we conducted single-nucleus transcriptomic and chromatin accessibility profiling of the adult cerebellar cortex in humans, chimpanzees, macaques, and marmosets. We revealed human-specific transcriptomic and regulatory features, particularly those involved in synaptogenesis. Notably, we identified an enrichment of the sperm receptor zona pellucida glycoprotein 2 (ZP2) and its potential interactors, known for their roles in gamete interaction, in human granule cells. Experimental data show that ZP2 expression in human granule cells is induced by pontine mossy fibers, reducing synaptic proteins at pontocerebellar glomerular synapses, and decreasing cerebellar neuron electrophysiological activity. This unexpected co-option of ZP2 in human-specific synapse regulation provides insights into the evolutionary specialization of the human cerebellum.

Brain evolution↗

PubMed2025

Dysregulation of mTOR signalling is a converging mechanism in lissencephaly.

Cerebral cortex development in humans is a highly complex and orchestrated process that is under tight genetic regulation. Rare mutations that alter gene expression or function can disrupt the structure of the cerebral cortex, resulting in a range of neurological conditions1. Lissencephaly ('smooth brain') spectrum disorders comprise a group of rare, genetically heterogeneous congenital brain malformations commonly associated with epilepsy and intellectual disability2. However, the molecular mechanisms underlying disease pathogenesis remain unknown. Here we establish hypoactivity of the mTOR pathway as a clinically relevant molecular mechanism in lissencephaly spectrum disorders. We characterized two types of cerebral organoid derived from individuals with genetically distinct lissencephalies with a recessive mutation in p53-induced death domain protein 1 (PIDD1) or a heterozygous chromosome 17p13.3 microdeletion leading to Miller-Dieker lissencephaly syndrome (MDLS). PIDD1-mutant organoids and MDLS organoids recapitulated the thickened cortex typical of human lissencephaly and demonstrated dysregulation of protein translation, metabolism and the mTOR pathway. A brain-selective activator of mTOR complex 1 prevented and reversed cellular and molecular defects in the lissencephaly organoids. Our findings show that a converging molecular mechanism contributes to two genetically distinct lissencephaly spectrum disorders.

Humans↗