Molecular Genetic Basis Research Articles

Small, but mitey: investigating the molecular genetic basis formite domatia development and intraspecific variation in Vitisriparia using transcriptomics.

Here, we investigated the molecular genetic basis of mite domatia, structures on the underside of leaves that house mutualistic mites, and intraspecific variation in domatia size in Vitis riparia (riverbank grape). Domatia and leaf traits were measured, and the transcriptomes of mite domatia from two genotypes of V. riparia with distinct domatia sizes were sequenced to investigate the molecular genetic pathways that regulate domatia development and intraspecific variation in domatia traits. Key trichome regulators as well as auxin and jasmonic acid are involved in domatia development. Genes involved in cell wall biosynthesis, biotic interactions, and molecule transport/metabolism are upregulated in domatia, consistent with their role in domatia development and function. This work is one of the first to date that provides insight into the molecular genetic bases of mite domatia. We identified key genetic pathways involved in domatia development and function, and uncovered unexpected pathways that provide an avenue for future investigation. We also found that intraspecific variation in domatia size in V. riparia seems to be driven by differences in overall leaf development between genotypes.

Genetic aspects of taste formation

The article discusses the molecular genetic basis of taste development which determines the peculiarity of perception of sweet, salty, sour, bitter and high-protein food (umami). The genes TAS1R3, FTO, GLUT2, FGF21, GNAT3 are responsible for individual perception of sugar volume. Serum FGF21 levels are significantly elevated in obese patients and in patients with type 2 diabetes mellitus which presumably indicates a state of resistance to FGF21. Given the role of refined sugars in the development of diseases, the use of foods with a reduced content or complete absence of added sugar is a worldwide trend, especially necessary in the nutrition of children. During genome-wide sequencing for 39 patients aged 15-18 years, FGF21 gene polymorphism was detected in 27 adolescents (69 %) without gender identity. Almost all patients with FGF21 gene polymorphism showed a high addiction to sweet foods. Currently, the existence of a sixth taste is being debated, it is ammonium chloride, whose receptors are regulated by the Otop1 gene which is also responsible for the identification of sour taste.

A Next-Generation Combinatorial Genomic Strategy Scans Genomic Loci Governing Heat Stress Tolerance in Chickpea.

In the wake of rising earth temperature, chickpea crop production is haunted by the productivity crisis. Chickpea, a cool season legume manifests tolerance in several agro-physiological level, which is complex quantitative in nature, and regulated by multiple genes and genetic networks. Understanding the molecular genetic basis of this tolerance and identifying key regulators can leverage chickpea breeding against heat stress. This study employed a genomics-assisted breeding strategy utilizing multi-locus GWAS to identify 10 key genomic regions linked to traits contributing to heat stress tolerance in chickpea. These loci subsequently delineated few key candidates and hub regulatory genes, such as RAD23b, CIPK25, AAE19, CK1 and WRKY40, through integrated genomics, transcriptomics and interactive analyses. The differential transcript accumulation of these identified candidates in contrasting chickpea accessions suggests their potential role in heat stress tolerance. Differential ROS accumulation along with their scavengers' transcript abundance aligning with the expression of identified candidates in the contrasting chickpea accessions persuade their regulatory significance. Additionally, their functional significance is ascertained by heterologous expression and subsequent heat stress screening. The high confidence genomic loci and the superior genes and natural alleles delineated here has great potential for swift genomic interventions to enhance heat resilience and yield stability in chickpea.

Integrated Phenotypic Physiology and Transcriptome Analysis Revealed the Molecular Genetic Basis of Anthocyanin Accumulation in Purple Pak-Choi

Purple Pak-choi is rich in anthocyanins, which have both ornamental and edible health functions, and has been used more and more widely in facility cultivation. In order to further clarify the molecular mechanism of purple Pak-choi, two Pak-choi inbred lines (‘PQC’ and ‘HYYTC’) were selected for the determination of pigment content and transcriptome analysis, and the key genes controlling the formation of purple character in leaves of Pak-choi were discovered. The results of pigment determination showed that the anthocyanin content of ‘PQC’ was 0.29 mg/g, which was about 100 times than ‘HYYTC’; The chlorophyll content of ‘HYYTC’ was 2.25 mg/g, while ‘PQC’ only contained 1.05 mg/g. A total of 20 structural genes related to anthocyanin biosynthesis and 28 transcriptional regulatory genes were identified by transcriptome analysis. Weighted gene co-expression network analysis (WGCNA) was used to construct the weight network analysis map of 14 genes. The results showed that the cinnamate hydroxylase gene (BraA04002213, BrC4H3), flavanone-3- hydroxylase (BraA09004531, BrF3H1), and chalcone synthetase (BraA10002265, BrCHS1) were the core genes involved in the anthocyanin synthesis pathway of purple Pak-choi. The results identified the key genes controlling the formation of purple leaf traits, which laid a foundation for further analysis of the molecular mechanism of anthocyanin accumulation in purple Pak-choi and provided a theoretical basis for leaf color regulation.

Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma.

Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely uncertain. This study aimed to investigate some novel prognostic biomarkers in HCC by using proteogenomic and transcriptomic analysis and explore the potential role of specific prognostic genes in HCC. Here, we have presented a proteogenomic analysis of 10 pairs of HCC. Protein co-expression and pathway analysis were performed to investigate the biological characteristics of HCC. Protein and mRNA expression profiles of multi-cohorts were integrated to detect novel prognostic protein markers of HCC. The carcinogenic roles of candidate prognostic markers were further evaluated by MTS assay, colony formation, monolayer wound healing assay, and xenograft models. A total of 2086 proteins with significantly different expressions were detected in HCC. Pathways related to oncogenic signaling and insulin-related metabolism have been found to be dysregulated and differentially regulated in HCC. We have identified the novel prognostic biomarkers, KIF5B, involved in liver metabolic reprogramming. The biomarkers were identified using multivariable COX regression analysis from two independent proteomic datasets (Fudan Cohort and our recruited cohort) and the TCGA mRNA database. Both the protein and mRNA up-regulation of KIF5B have been found to be associated with a poor clinical outcome in HCC. Insulin activated the protein expression of KIF5B in HCC. Knocking out KIF5B expression by sgRNA decreased the protein expression of FASN and SCD1 and the intracellular triglyceride concentration. Silencing KIF5B suppressed HCC cell proliferation and colony formation in vitro, as well as HCC growth in xenograft models. Our findings have suggested KIF5B protein to function as a novel prognostic biomarker in HCC. KIF5B expression has been found to activate the AKT/mTOR pathway and reprogram triglyceride metabolism, leading to HCC development. Targeting KIF5B may be an effective strategy in the clinical treatment of HCC.

Global research landscape of Peutz-Jeghers syndrome and successful endoscopic management of intestinal intussusception in patients with recurrent laparotomies.

Peutz-Jeghers syndrome (PJS) has brought significant physical, psychological and economic burdens on the patients and their families due to its early onset, diagnostic and therapeutic challenges and increased recurrence risk. To explore the current research status and emerging hotspots of PJS. Studies on PJS published during 1994-2023 were gathered based on Web of Science Core Collection. Additionally, a case of PJS-induced intestinal intussusception, successfully treated with endoscopic methods despite three laparotomies, was highlighted. Comprehensive bibliometric and visual analysis were conducted with VOSviewer, R and CiteSpace. Altogether 1760 studies were identified, indicating a steady increase in the publication number. The United States had the highest influence, whereas the University of Helsinki emerged as the leading institution, and Aaltonen LA from the University of Helsinki was the most prolific author. Cancer Research, Oncogene and Endoscopy were the top three journals based on H-index. Keyword burst direction analysis revealed that "cancer risk", "management", "surveillance" and "familial pancreatic cancer" were the potential hotspots for investigation. Additionally, "early detection", "capsule endoscopy", "clinical management", "double-balloon endoscopy", "familial pancreatic cancer" and "molecular genetic basis" were identified as the key clusters of co-cited references. Endoscopic polypectomy remained effective on resolving intestinal intussusception in patients who underwent three previous laparotomies. In the last three decades, global publications related to PJS show a steadily increasing trend in number. Endoscopic management is currently a research hotspot.

A Novel Molecular-Genetic Approach to the Monitoring of Dynamics of Mitochondrial Function Improvement during Treatment.

Making a correct genetically based diagnosis in patients with diseases associated with mitochondrial dysfunction can be challenging both genetically and clinically, as can further management of such patients on the basis of molecular-genetic data assessing the state of their mitochondria. In this opinion article, we propose a novel approach (which may result in a clinical protocol) to the use of a precise molecular-genetic tool in order to monitor the state of mitochondria (which reflects their function) during treatment of certain conditions, by means of not only signs and symptoms but also the molecular-genetic basis of the current condition. This is an example of application of personalized genomic medicine at the intersection of a person's mitochondrial genome information and clinical care. Advantages of the proposed approach are its relatively low cost (compared to various types of sequencing), an ability to use samples with a low input amount of genetic material, and rapidness. When this approach receives positive outside reviews and gets an approval of experts in the field (in terms of the standards), it may then be picked up by other developers and introduced into clinical practice.

Metabolism of 2,4-D in plants: comparative analysis of metabolic detoxification pathways in tolerant crops and resistant weeds.

The commercialization of 2,4-D (2,4-dichlorophenoxyacetic acid) latifolicide in 1945 marked the beginning of the selective herbicide market, with this active ingredient playing a pivotal role among commercial herbicides due to the natural tolerance of monocots compared with dicots. Due to its intricate mode of action, involving interactions within endogenous auxin signaling networks, 2,4-D was initially considered a low-risk herbicide to evolve weed resistance. However, the intensification of 2,4-D use has contributed to the emergence of 2,4-D-resistant broadleaf weeds, challenging earlier beliefs. This review explores 2,4-D tolerance in crops and evolved resistance in weeds, emphasizing an in-depth understanding of 2,4-D metabolic detoxification. Nine confirmed 2,4-D-resistant weed species, driven by rapid metabolism, highlight cytochrome P450 monooxygenases in Phase I and glycosyltransferases in Phase II as key enzymes. Resistance to 2,4-D may also involve impaired translocation associated with mutations in auxin/indole-3-acetic acid (Aux/IAA) co-receptor genes. Moreover, temperature variations affect 2,4-D efficacy, with high temperatures increasing herbicide metabolism rates and reducing weed control, while drought stress did not affect 2,4-D efficacy. Research on 2,4-D resistance has primarily focused on non-target-site resistance (NTSR) mechanisms, including 2,4-D metabolic detoxification, with limited exploration of the inheritance and genetic basis underlying these traits. Resistance to 2,4-D in weeds is typically governed by a single gene, either dominant or incompletely dominant, raising questions about gain-of-function or loss-of-function mutations that confer resistance. Future research should unravel the physiological and molecular-genetic basis of 2,4-D NTSR, exploring potential cross-resistance patterns and assessing fitness costs that may affect future evolution of auxin-resistant weeds. © 2024 Society of Chemical Industry.

Quantitative Trait Loci Mapping and Candidate Gene Analysis for Fiber Quality Traits in Upland Cotton

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 13 major effect QTLs that contributed more than 10% toward phenotypic variation (PV) and 9 stable QTLs that could be repeatedly mapped in different generations. Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosomes D1 and D11. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18–21.45% of PV and qFS-A11-1 in F2:3, F2:4, and F2:5 with 6.05–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, while Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

The genetic basis of incipient sexual isolation in Drosophila melanogaster.

Speciation is a fundamental evolutionary process but the genetic changes accompanying speciation are difficult to determine since true species do not produce viable and fertile offspring. Partially reproductively isolated incipient species are useful for assessing genetic changes that occur prior to speciation. Drosophila melanogaster from Zimbabwe, Africa are partially sexually isolated from other D. melanogaster populations whose males have poor mating success with Zimbabwe females. We used the North American D. melanogaster Genetic Reference Panel (DGRP) to show that there is significant genetic variation in mating success of DGRP males with Zimbabwe females, to map genetic variants and genes associated with variation in mating success and to determine whether mating success to Zimbabwe females is associated with other quantitative traits previously measured in the DGRP. Incipient sexual isolation is highly polygenic and associated with the common African inversion In(3R)K and the amount of the sex pheromone 5,9-heptacosadiene in DGRP females. We functionally validated the effect of eight candidate genes using RNA interference to provide testable hypotheses for future studies investigating the molecular genetic basis of incipient sexual isolation in D. melanogaster.

Optix and cortex/ivory/mir-193 again: the repeated use of two mimicry hotspot loci.

The extent to which evolution is repeatable has been a debated topic among evolutionary biologists. Although rewinding the tape of life perhaps would not lead to the same outcome every time, repeated evolution of analogous genes for similar functions has been extensively reported. Wing phenotypes of butterflies and moths have provided a wealth of examples of gene re-use, with certain 'hotspot loci' controlling wing patterns across diverse taxa. Here, we present an example of convergent evolution in the molecular genetic basis of Batesian wing mimicry in two Hypolimnas butterfly species. We show that mimicry is controlled by variation near cortex/ivory/mir-193, a known butterfly hotspot locus. By dissecting the genetic architecture of mimicry in Hypolimnas misippus and Hypolimnas bolina, we present evidence that distinct non-coding regions control the development of white pattern elements in the forewing and hindwing of the two species, suggesting independent evolution, and that no structural variation is found at the locus. Finally, we also show that orange coloration in H. bolina is associated with optix, a well-known patterning gene. Overall, our study once again implicates variation near the hotspot loci cortex/ivory/mir-193 and optix in butterfly wing mimicry and thereby highlights the repeatability of adaptive evolution.

Transformation of Terpenoids and Steroids Using Actinomycetes of the Genus Rhodococcus.

Terpenoids and steroids are secondary plant and animal metabolites and are widely used to produce highly effective pharmacologically significant compounds. One of the promising approaches to the transformation of these compounds to form bioactive metabolites is their transformation using microorganisms. Rhodococcus spp. are one of the most developed objects in biotechnology due to their exceptional metabolic capabilities and resistance to extreme environmental conditions. In this review, information on the processes of biotransformation of terpenoid and steroid compounds by actinomycetes of the genus Rhodococcus and their molecular genetic bases are most fully collected and analyzed for the first time. Examples of the use of both native whole-cell catalysts and mutant strains and purified enzyme systems for the production of derivatives of terpenoids and steroids are given.

Pathological Defects in a Drosophila Model of Alzheimer's Disease and Beneficial Effects of the Natural Product Lisosan G.

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize the onset of the disease pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on amyloid β (Aβ)-peptide production and accumulation and, consequently, on AD pathogenesis. We exploited the fruit fly Drosophila melanogaster model of AD to evaluate in vivo the beneficial properties of Lisosan G, a fermented powder obtained from organic whole grains, on the intracellular Aβ-42 peptide accumulation and related pathological phenotypes of AD. Our data showed that the Lisosan G-enriched diet attenuates the production of neurotoxic Aβ peptides in fly brains and reduces neuronal apoptosis. Notably, Lisosan G exerted anti-oxidant effects, lowering brain levels of reactive oxygen species and enhancing mitochondrial activity. These aspects paralleled the increase in autophagy turnover and the inhibition of nucleolar stress. Our results give support to the use of the Drosophila model not only to investigate the molecular genetic bases of neurodegenerative disease but also to rapidly and reliably test the efficiency of potential therapeutic agents and diet regimens.

Build-A-Genome and the “awesome power of undergraduates”

Abstract The Elizabeth W. Jones Award for Excellence in Education recognizes individuals or groups who have had significant, sustained impact on genetics education at any level, from K-12 through graduate school and beyond. The 2024 Elizabeth W. Jones Award for Excellence in Education recipient Jef Boeke considers himself a geneticist turned engineer. He transformed his landmark synthetic yeast genome project into a research-heavy teaching course, revolutionizing molecular biology and genetics education. The Build-A-Genome course was developed to teach students basic practical molecular genetics while also providing the raw materials for a global genome synthesis project, Yeast 2.0. The course evolved over two decades to reflect the changing needs and opportunities for the project and the development of new technologies. In addition to educating a generation of college and high school students in a new way, it also developed a cadre of educators who developed similar courses and projects at a wide variety of research and educational institutions.

Molecular Genetic Basis of Collagen Used in Chronic Diabetic Wounds

The review of the world literature, is devoted to the role of collagen in the process of wound healing. The problems of epidemiology of chronic wounds and ulcers of various genesis, physiology and pathophysiology of wound healing phases are considered. The pathogenetic role of different types of collagen, as well as the mechanisms of collagen, macrophage, fibroblasts, matrix metalloproteinases and other cytokines in healing ulcers are discussed. The prospects of development and use of medical products and preparations based on collagen in the treatment of patients with chronic wounds and ulcers are shown. The results of clinical studies on the effectiveness of collagen with preserved (native) and unsaved (fractionated) structure are presented. The advantages of using native collagen in the treatment of diabetic foot syndrome are demonstrated

Genetics of Hypertension: From Monogenic Analysis to GETomics.

Arterial hypertension is the most frequent cardiovascular risk factor all over the world, and it is one of the leading drivers of the risk of cardiovascular events and death. It is a complex trait influenced by heritable and environmental factors. To date, the World Health Organization estimates that 1.28 billion adults aged 30-79 years worldwide have arterial hypertension (defined by European guidelines as office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg), and 7.1 million die from this disease. The molecular genetic basis of primary arterial hypertension is the subject of intense research and has recently yielded remarkable progress. In this review, we will discuss the genetics of arterial hypertension. Recent studies have identified over 900 independent loci associated with blood pressure regulation across the genome. Comprehending these mechanisms not only could shed light on the pathogenesis of the disease but also hold the potential for assessing the risk of developing arterial hypertension in the future. In addition, these findings may pave the way for novel drug development and personalized therapeutic strategies.

Evolutionary history and biological adaptation of Han Chinese people on the Mongolian Plateau

Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis of adaptive traits or complex diseases. Recent ancient genome data allow us to trace how key traits evolved in different human populations over time, connecting ancient population history with disease susceptibility in western Eurasians. To fill this gap in eastern Eurasians and provide deep insights into the evolutionary history of the population-specific genetic basis of complex biological traits, we explored the evolutionary basis of adaptive traits in one integrative modern and ancient genomic database, including 225 out of 5583 genomes first reported here. We comprehensively characterized the demographic history and biological adaptation of Han Chinese individuals on the Mongolian Plateau based on the allele frequency spectrum and haplotype-resolved fragments. We found strong genetic homogeneity among geographically different Han populations from Inner Mongolia (IMH). We reconstructed their admixture models and demographic events, revealing that IMH had a close genetic relationship with ancient millet farmers and obtained additional gene flow from Altaic-speaking populations. The enrichment of selected candidate genes suggested that essential metabolism-related genes promoted the rapid adaptation of eastern Eurasians to ancient environmental shifts and dietary changes during agricultural innovations. Evolutionary trajectory reconstruction of metabolism-related genes of methylenetetrahydrofolate reductase (MTHFR) and fatty acid desaturase 1 (FADS1) suggested that ancient dietary shifts during the Neolithic transition period promoted the differentiated metabolic rate of folate and fatty acid. We revealed the polygenicity of biological adaptation traits and the pleiotropy of adaptive genes, indicating that complex recent polygenic adaptations, genetic interactions, and genotype–phenotype correlations have contributed to the genetic architecture of complex traits in eastern Eurasians.

The construction of genetics teaching resources related to colour blindness and their application in genetics teaching.

Red-green colour blindness is a classic example for the teaching of X-linked recessive inheritance in genetics course. However, there are lots of types of color vision deficiencies besides red-green colour blindness. Different color vision deficiencies caused by different genes may have different modes of inheritance. In recent years, many research achievements on colour blindness have been made. These achievements could be used as teaching resources in genetics course. Here, we summarize the construction of genetics teaching resources related to colour blindness and their application in genetics teaching in several chapters such as introduction, cellular and molecular basis of genetics, sex-linked inheritance, chromosomal aberration, gene mutation and advances in genetics. Teacher could use the resources in class or after class with different teaching methods such as questioning teaching method and task method. It may expand students' academic horizons and inspire students' interest in genetics besides grasping basic genetic knowledge.

Pleiotropy, epistasis and the genetic architecture of quantitative traits.

Pleiotropy (whereby one genetic polymorphism affects multiple traits) and epistasis (whereby non-linear interactions between genetic polymorphisms affect the same trait) are fundamental aspects of the genetic architecture of quantitative traits. Recent advances in the ability to characterize the effects of polymorphic variants on molecular and organismal phenotypes in human and model organism populations have revealed the prevalence of pleiotropy and unexpected shared molecular genetic bases among quantitative traits, including diseases. By contrast, epistasis is common between polymorphic loci associated with quantitative traits in model organisms, such that alleles at one locus have different effects in different genetic backgrounds, but is rarely observed for human quantitative traits and common diseases. Here, we review the concepts and recent inferences about pleiotropy and epistasis, and discuss factors that contribute to similarities and differences between the genetic architecture of quantitative traits in model organisms and humans.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation.

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.