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Liang, D.

Publications and source records attributed to Liang, D..

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Evaluating the Impact of Purifying Selection on Species-level Molecular Dating

The neutral theory of molecular evolution suggests that the constancy of the molecular clock relies on the neutral condition. Thus, purifying selection, the most common type of natural selection, could influence the constancy of the molecular clock, and the use of genes/sites under purifying selection may produce less reliable molecular dating results. However, in current practices of species-level molecular dating, some researchers prefer to select slowly evolving genes/sites to avoid the potential impact of substitution saturation. These genes/sites are generally under a strong influence of purifying selection. Here, from the data of 23 published mammal genomes, we constructed datasets under various selective constraints. We compared the differences in branch lengths and time estimates among these datasets to investigate the impact of purifying selection on species-level molecular dating. We found that as the selective constraint increases, terminal branches are extended, which introduces biases into the result of species-level molecular dating. This result suggests that in species-level molecular dating, the impact of purifying selection should be taken into consideration, and researchers should be more cautious with the use of genes/sites under purifying selection.

evolutionary biology

The genomic diversification of clonally propagated grapevines

Vegetatively propagated clones accumulate somatic mutations. The purpose of this study was to better understand the consequences of clonal propagation and involved defining the nature of somatic mutations throughout the genome. Fifteen Zinfandel winegrape clone genomes were sequenced and compared to one another using a highly contiguous genome reference produced from one of the clones, Zinfandel 03.\n\nThough most heterozygous variants were shared, somatic mutations accumulated in individual and subsets of clones. Overall, heterozygous mutations were most frequent in intergenic space and more frequent in introns than exons. A significantly larger percentage of CpG, CHG, and CHH sites in repetitive intergenic space experienced transition mutations than genic and non-repetitive intergenic spaces, likely because of higher levels of methylation in the region and the increased likelihood of methylated cytosines to spontaneously deaminate. Of the minority of mutations that occurred in exons, larger proportions of these were putatively deleterious when they occurred in relatively few clones.\n\nThese data support three major conclusions. First, repetitive intergenic space is a major driver of clone genome diversification. Second, clonal propagation is associated with the accumulation of putatively deleterious mutations. Third, the data suggest selection against deleterious variants in coding regions such that mutations are less frequent in coding than noncoding regions of the genome.

genomics

The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ

The female upper reproductive tract, including the uterus, fallopian tubes and ovaries, is believed to be a sterile environment. With the improvement of bacterial detection, the theory of the sterile female upper reproductive tract has been frequently challenged in recent years. However, thus far, no researchers have used ovaries as study targets. Six women who were diagnosed with ovarian cancer were included in the cancer group, and ten women who were diagnosed with a noncancerous ovarian condition (including three patients with uterine myoma and seven patients with uterine adenomyosis) were included in the control group. Immunohistochemistry staining using an antibacterial lipopolysaccharide (LPS) antibody was used to confirm the presence of bacteria in the ovarian tissues. In addition, 16S rRNA sequencing was used to compare the differences in the bacteria between ovarian cancer tissues and noncancerous ovarian tissues. BugBase and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to predict the functional composition of the bacteria. Bacterial LPS was present in ovarian cancer tissue and noncancerous ovarian tissue, which implied the presence of bacteria in ovarian tissue. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues. Author summaryAbdominal solid viscera have always been believed to be absolutely sterile. With the improvement of bacterial detection, this concept is being challenged. Researchers found some bacteria existed in endometrial diseases, the question of whether the ovaries are sterile is still unclear. Therefore, we assume that the bacteria in ovarian tissue are associated with ovarian cancer. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues.

microbiology

Hyocholic acid species and the risk of type 2 diabetes

Hyocholic acid (HCA) and its derivatives are found in only trace amounts in human blood, but constitute approximately 76 % of the bile acid (BA) pool in the pig, a species known for its exceptional resistance to type 2 diabetes mellitus (T2DM). Here we show that HCA species play a crucial role in maintaining glucose homeostasis and preventing T2DM. We found that in two cohort studies (n=1,213), both obesity and diabetes were associated with lower serum concentrations of HCA species. Serum HCA levels in apparently healthy individuals (n=132) were found to be strong predictors for metabolic health 10 years later. Oral administration of HCA increased serum fasting GLP-1, to a greater extent than metformin, in healthy and diabetic mouse models. HCA upregulated GLP-1 secretion in intestinal enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor, a unique mechanism that is not found in other BA species.

systems biology