Biology subjects

Lo, C.-Y.

Publications and source records attributed to Lo, C.-Y..

6 recordsLinked to original sources

bioRxiv2024

How weedy Arabidopsis thaliana dominated the world: ancestral variation and polygenic adaptation

The composition of a species could change with demographic turnovers, where dominant populations quickly expanded and replaced others. However, whether such events have a genetic basis remains to be investigated. Previous studies showed that Arabidopsis thaliana experienced a significant demographic turnover, where "non-relicts" replaced "relicts" throughout Eurasia. Here, we showed that non-relicts have smaller seeds, more seeds per fruit, and a higher germination rate, making them more competitive over relicts. Using a unique population enriching relict alleles while minimizing population structure, we identified candidate loci and showed that such trait divergence was caused by the divergent sorting of multiple ancient haplotypes in a Mendelian gene and joint allele frequency change of polygenes affecting single-trait divergence and multi-trait covariance. This study is one of the few genetic investigations of species-wide demographic turnover, emphasizing the importance of processes different from the much-focused hard selective sweep.

evolutionary biology↗

bioRxiv2022

The clock gene Per1 expression may exert diurnal control over hippocampal memory consolidation

The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brains central pacemaker, satellite clocks have also been identified in other brain regions, such as the memory-relevant dorsal hippocampus. Although it is unclear how these satellite clocks contribute to brain function, one possibility is that they may serve to exert diurnal control over local processes. Within the hippocampus, for example, the local clock may contribute to time-of-day effects on memory. Here, we used the hippocampus-dependent Object Location Memory task to determine how memory is regulated across the day/night cycle in mice. First, we systematically determined which phase of memory (acquisition, consolidation, or retrieval) is modulated across the 24h day. We found that mice show better long-term memory performance during the day than at night, an effect that was specifically attributed to diurnal changes in memory consolidation, as neither memory acquisition nor memory retrieval fluctuated across the day/night cycle. Using RNA-sequencing we identified the circadian clock gene Period1 (Per1) as a key mechanism capable of supporting this diurnal fluctuation in memory consolidation, as Per1 oscillates in tandem with memory performance. We then show that local knockdown of Per1 within the dorsal hippocampus has no effect on either the circadian rhythm or sleep behavior, although previous work has shown this manipulation impairs memory. Thus, Per1 may independently function within the dorsal hippocampus to regulate memory in addition to its known role in regulating the circadian rhythm within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the dorsal hippocampus.

neuroscience↗

bioRxiv2022

Structural and Dynamic Basis of DNA Capture and Translocation by Mitochondrial Twinkle Helicase

Twinkle is the sole helicase responsible for mitochondrial DNA replication. Twinkle can selfload onto and unwind mitochondrial DNA. Nearly 60 mutations on Twinkle have been linked to human mitochondrial diseases. Using cryo-electron microscopy (cryo-EM) and High-speed atomic force microscope (HS-AFM), we obtained the atomic-resolution structure of a vertebrate Twinkle homolog with DNA and captured in real-time how Twinkle is self-loaded onto DNA. Our data highlight the essential role of the non-catalytic N-terminal domain of Twinkle. The N-terminal domain interacts with the helicase domain to stabilize Twinkle hexamers during translocation and the new domain-domain interface is a hotspot for disease-related mutations. The N-terminal domains can protrude approximately 5 nm to capture nearby DNA and initialize Twinkle loading onto DNA. Moreover, structural analysis and subunit doping experiments suggest that Twinkle hydrolyzes ATP stochastically, which explains the low efficiency of Twinkle DNA unwinding and implicates additional regulations of Twinkle during mitochondrial DNA replication.

biochemistry↗

bioRxiv2022

The climatic constrains of the historical global spread of mungbean

While the domestication history has been investigated in many crops, the process of cultivation range expansion and factors governing this process received relatively little attention. Here using mungbean (Vigna radiata var. radiata) as a test case, we investigated the genomes of more than one thousand accessions to illustrate climatic adaptations role in dictating the unique routes of cultivation range expansion. Despite the geographical proximity between South and Central Asia, genetic evidence suggests mungbean cultivation first spread from South Asia to Southeast, East, and finally reached Central Asia. Combining evidence from demographic inference, climatic niche modeling, plant morphology, and records from ancient Chinese sources, we showed that the specific route was shaped by the unique combinations of climatic constraints and farmer practices across Asia, which imposed divergent selection favoring higher yield in the south but short-season and more drought-tolerant accessions in the north. Our results suggest that mungbean did not radiate from the domestication center as expected purely under human activity, but instead the spread of mungbean cultivation is highly constrained by climatic adaptation, echoing the idea that human commensals are more difficult to spread through the south-north axis of continents.

evolutionary biology↗

bioRxiv2018

On the post-glacial spread of human commensal Arabidopsis thaliana: journey to the east

With the availability of more sequenced genomes, our understanding of the evolution and demographic history of the model plant Arabidopsis thaliana is rapidly expanding. Here we compile previously published data to investigate global patterns of genetic variation. While the Southeast African accessions were reported to be the most divergent among worldwide populations, we found accessions from Yunnan, China to be genetically close to the sub-Saharan accessions. Our further investigation of worldwide chloroplast genomes identified several deeply diverged haplogroups existing only in Eurasia, and the African populations have lower variation in many haplogroups they shared with the Eurasian populations. Bayesian inferences of chloroplast demography showed that representative haplogroups of Africa exhibited long-term stable population size, suggesting recent selective sweep or bottleneck is not able to explain the lower chloroplast variation in Africa. Taken together, these patterns cannot be easily explained by a single out-of-Africa event. Several Eurasian chloroplast haplogroups had rapid population growth since 10 kya, presumably reflecting the recent expansion of the weedy non-relicts across Eurasia. Our demographic analysis on a chromosomal region un-affected by relict introgression also suggested the European, Central Asian, and Chinese Yangtze populations diverged no earlier than 15 kya, in contrast to previous estimates of 45 kya inferred from whole genome that likely contains relict admixture. The most recent expansion is observed in the Yangtze population of China less than 2000 years ago. Similar to Iberia, the western end of non-relict expansion reported in our previous study, in this eastern end of Eurasia we find clear traces of gene flow between the Yangtze non-relicts and the Yunnan relicts. Genes under strong selection and previously suggested to contribute to adaptation in the Yangtze valley are enriched for traces of relict introgression, especially those related with biotic and immune responses. The results suggest the ability of non-relicts to obtain locally adaptive alleles through admixture with relicts is an important factor contributing to the rapid expansion across the environmental gradients spanning the eastern to the western coast of Eurasia.

evolutionary biology↗

bioRxiv2018

Topographic diversity of structural connectivity in schizophrenia

The neurobiological heterogeneity of schizophrenia is widely accepted, but it is unclear how mechanistic differences converge to produce the observed phenotype. Establishing a pathophysiological model that accounts for both heterogeneity and phenotypic similarity is essential to inform stratified treatment approaches. In this cross-sectional diffusion tensor imaging (DTI) study, we recruited 77 healthy controls (HC), and 71 patients with DSM-IV diagnosis of schizophrenia (SCZ), and reconstructed the structural connectivity of 90 brain regions covering entire cerebral cortex. We first confirmed the heterogeneity in structural connectivity by showing a reduced inter-individual similarity in SCZ compared with HC. Moreover, we found it was not possible to cluster patients into subgroups with shared patterns of dysconnectivity, indicating a high degree of mechanistic divergence in schizophrenia. Instead of the strength of connectivity between any particular brain regions, we investigated the diversity (or statistically, the variance) of the topographic distribution of the strength was reduced. HC had higher topographic diversity in whole brain structural connectivity compared to the patient group\n\n(P = 2 x 10-6, T = 4.96, Cohen'S d = 0.87). In 62 of the 90 brain regions, the topographic diversity was significantly reduced in patients compared to controls after FDR correction (<0.05). When topographic diversity was used as a discriminant feature for classification between patients and controls, we significantly (P = 4.29 x 10-24) improved the classification accuracy to 79.6% (sensitivity 78.3%, specificity 81.3%). This finding suggests highly individualized pattern of structural dysconnectivity underlying the heterogeneity of schizophrenia converges to a convergent common pathway as reduced topographic diversity for the clinical construct of the disease.

neuroscience↗