Biology subjects

Meng, D.

Publications and source records attributed to Meng, D..

24 records · Page 2Linked to original sources

bioRxiv2022

A refined characterization of large-scale genomic differences in the first complete human genome

The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release was a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet. Here, we identify 590 discrepant regions ([~]226 Mbp) in total. In addition to the previously reported non-syntenic regions, we identify 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool (SynPlotter). The discrepant regions ([~]20.4 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where copy number variation are likely associated with various human disease and disease susceptibility, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region--the KLRC gene cluster--shows that the depletion of KLRC2 by a single deletion event is associated with natural killer cell differentiation in [~]20% of humans. Meanwhile, the rapid amino acid replacements within KLRC3 is consistent with the action of natural selection during primate evolution. Our study furthers our understanding of the large-scale structural variation differences between these two crucial human reference genomes and future interpretation of studies of human genetic variation.

genomics↗

bioRxiv2021

Local and global chemical shaping of bacterial communities by redox potential

Thermodynamics predicts a positive correlation between environmental redox potential and oxidation state of molecules; if found for microbial communities it would imply a new kind of deterministic eco-evolutionary process. This study examines evidence for local- and global-scale correlations between oxidation-reduction potential (ORP or Eh) in environmental samples and carbon oxidation state (ZC) of estimated bacterial and archaeal community proteomes. Seventy-nine public datasets for seven environment types (river & seawater, lake & pond, alkaline spring, hot spring, groundwater, sediment, and soil) were analyzed. Taxonomic abundances inferred from high-throughput 16S rRNA gene sequences were combined with NCBI Reference Sequence (RefSeq) proteomes to estimate the amino acid compositions and chemical formulas (CcHhNnOoSs) of community proteomes, which yield ZC. Alkaline hot springs have the lowest ZC for both bacterial and archaeal domains of any environment. Positive global correlations between redox potential and ZC are found for bacterial communities in lake & pond, groundwater, and soil environments, but not archaeal communities, suggesting a broad ecological signal of chemical shaping in Bacteria.

ecology↗

bioRxiv2021

Generalizable predictive modeling of semantic processing ability from functional brain connectivity

Semantic processing (SP) is one of the critical abilities of humans for representing and manipulating meaningful and conceptual information. Neuroimaging studies of SP typically collapse data from many subjects, but both its neural organization and behavioral performance vary between individuals. It is not yet understood whether and how the individual variabilities in neural organizations contribute to the individual differences in SP behaviors. Here we aim to identify the neural signatures underlying SP variabilities by analyzing individual functional connectivity (FC) patterns based on a large-sample Human Connectome Project (HCP) dataset and rigorous predictive modeling. We used a two-stage predictive modeling approach to build an internally cross-validated model and to test the models generalizability with unseen data from different HCP sub-populations and task states as well as other out-of-sample datasets that are independent of the HCP. FC patterns within a putative semantic brain network were significantly predictive of individual SP scores summarized from five semantic tasks. This cross-validated predictive model can be used to predict unseen HCP data. The model generalizability was enhanced with FCs in language tasks than resting state and other task states and was better for females than males. The model constructed from the HCP dataset can be generalized to two independent cohorts that participated in different semantic tasks. FCs connecting to the Perisylvian language network show the most reliable contributions to predictive modeling and the out-of-sample generalization. These findings contribute to our understanding of the neural sources of individual differences in SP, which potentially lay the foundation for personalized education and improve intervention practice for patients with SP and language deficits.

neuroscience↗

bioRxiv2018

Adaptive Reduction of Male Gamete Number in a Selfing Species

The number of male gametes produced is critical for reproductive success and varies greatly between and within species1-3. Evolutionary reduction of male gamete production has been widely reported in plants as a hallmark of the selfing syndrome, as well as in humans. Such a reduction may simply represent deleterious decay4-7, but evolutionary theory predicts that breeding systems could act as a major selective force on male gamete number: while large numbers of sperm should be produced in highly promiscuous species because of male-male gamete competition1, reduced sperm numbers may be advantageous at lower outcrossing rates because of the cost of gamete production. Here we used genome-wide association study (GWAS) to show a signature of polygenic selection on pollen number in the predominantly selfing plant Arabidopsis thaliana. The top associations with pollen number were significantly more strongly enriched for signatures of selection than those for ovule number and 107 phenotypes analyzed previously, indicating polygenic selection8. Underlying the strongest association, responsible for 20% of total pollen number variation, we identified the gene REDUCED POLLEN NUMBER 1 affecting cell proliferation in the male germ line. We validated its subtle but causal allelic effects using a quantitative complementation test with CRISPR-Cas9-generated null mutants in a nonstandard wild accession. Our results support polygenic adaptation underlying reduced male gamete numbers.

evolutionary biology↗

bioRxiv2017

SLFL Genes Participate in the Ubiquitination and Degradation of S-RNase in Self-Compatible Chinese Peach

The gametophytic self-incompatibility (SI) mediated by S-RNase of Rosaceae, Solanaceae and Plantaginaceae, is controlled by two tightly linked genes located at highly polymorphic S-locus: the S-RNase for pistil specificity and the F-box gene (SFB/SLF) for pollen specificity, respectively. The F-box gene of peach (Prunus persica) is S haplotype-specific F-box (SFB). In this study, we selected 37 representative varieties according to the evolution route of peach and identified their S genotypes. We cloned pollen determinant genes mutant PperSFB1m, PperSFB2m, PperSFB4m and normal PperSFB2, and style determinant genes S1-RNase, S2-RNase, S2m-RNase and S4-RNase. Mutant PperSFBs were translated terminated prematurely because of fragment insertion. Yeast two-hybrid showed that mutant PperSFBs and normal PperSFB2 interacted with all S-RNases. Normal PperSFB2 was divided into four parts: box, box-V1, V1-V2 and HVa-HVb. Protein interaction analyses showed that the box portion did not interact with S-RNases, both of the box-V1 and V1-V2 had interactions with S-RNases, while the hypervariable region of PperSFB2 HVa-HVb only interacted with S2-RNase. Bioinformatics analysis of peach genome revealed that there were other F-box genes located at S-locus, and of which three F-box genes were specifically expressed in pollen, namely PperSLFL1, PperSLFL2 and PperSLFL3, respectively. Phylogenetic analysis showed that PperSFBs and PperSLFLs were classified into two different clades. Yeast two-hybrid analysis revealed that as with PperSFBs, the three F-box proteins interacted with PperSSK1. Yeast two-hybrid and BiFC showed that PperSLFLs interacted with S-RNases with no allelic specificity. In vitro ubiquitination assay showed that PperSLFLs could tag ubiquitin molecules to PperS-RNases. In all, the above results suggest that three PperSLFLs are the appropriate candidates for the general inhibitor, which would inactivate the S-RNases in pollen tubes, and the role of three PperSLFL proteins is redundant, as S-RNase repressors involved in the self-incompatibility of peach.

molecular biology↗

bioRxiv2017

Patterns of polymorphism at the self-incompatibility locus in 1,083 Arabidopsis thaliana genomes

Although the transition to selfing in the model plant Arabidopsis thaliana involved the loss of the self-incompatibility (SI) system, it clearly did not occur due to the fixation of a single inactivating mutation at the locus determining the specificities of SI (the S-locus). At least three groups of divergent haplotypes (haplogroups), corresponding to ancient functional S-alleles, have been maintained at this locus, and extensive functional studies have shown that all three carry distinct inactivating mutations. However, the historical process of loss of SI is not well understood, in particular its relation with the last glaciation. Here, we took advantage of recently published genomic re-sequencing data in 1,083 Arabidopsis thaliana accessions that we combined with BAC sequencing to obtain polymorphism information for the whole S-locus region at a species-wide scale. The accessions differed by several major rearrangements including large deletions and inter-haplogroup recombinations, forming a set of haplogroups that are widely distributed throughout the native range and largely overlap geographically. Relict A. thaliana accessions that directly derive from glacial refugia are polymorphic at the S-locus, suggesting that the three haplogroups were already present when glacial refugia from the last Ice Age became isolated. Inter-haplogroup recombinant haplotypes were highly frequent, and detailed analysis of recombination breakpoints suggested multiple independent origins. These findings suggest that the complete loss of SI in A. thaliana involved independent self-compatible mutants that arose prior to the last Ice Age, and experienced further rearrangements during post-glacial colonization.

evolutionary biology↗