scholarly journals Tissue-specific impacts of aging and genetics on gene expression patterns in humans

2021 ◽  
Author(s):  
Ryo Yamamoto ◽  
Ryan Chung ◽  
Juan Manuel Vazquez ◽  
Huanjie Sheng ◽  
Philippa Steinberg ◽  
...  

Age is the primary risk factor for many common human diseases including heart disease, Alzheimer's dementias, cancers, and diabetes. Determining how and why tissues age differently is key to understanding the onset and progression of such pathologies. Here, we set out to quantify the relative contributions of genetics and aging to gene expression patterns from data collected across 27 tissues from 948 humans. We show that gene expression patterns become more erratic with age in several different tissues reducing the predictive power of expression quantitative trait loci. Jointly modelling the contributions of age and genetics to transcript level variation we find that the heritability (h2) of gene expression is largely consistent among tissues. In contrast, the average contribution of aging to gene expression variance varied by more than 20-fold among tissues with R2age > h2 in 5 tissues. We find that the coordinated decline of mitochondrial and translation factors is a widespread signature of aging across tissues. Finally, we show that while in general the force of purifying selection is stronger on genes expressed early in life compared to late in life as predicted by Medawar's hypothesis, a handful of highly proliferative tissues exhibit the opposite pattern. In contrast, gene expression variation that is under genetic control is strongly enriched for genes under relaxed constraint. Together we present a novel framework for predicting gene expression phenotypes from genetics and age and provide insights into the tissue-specific relative contributions of genes and the environment to phenotypes of aging.

1970 ◽  
Vol 27 (2) ◽  
pp. 131
Author(s):  
D K Ayer, K G Modha, V B Parekh, R K Patel, V Ramtekey, A P Bhuriya

Two turmeric (Curcuma longa L.) cultivars differing in curcumin content viz GNT-2 (4.6 % curcumin) and NDH-98 (1.6% curcumin) were selected for comparative gene expression study in association with total curcumin contents. Sampling was done at six months after planting in open field condition. Differential gene expression patterns were observed between two cultivars by reverse transcription quantitative real time polymerase chain reaction (RT-qPCR), and total curcumin contents were quantified using high performance liquid chromatography (HPLC). Low curcumin yielding cultivar, NDH-98, exhibited higher expression of DCS and CURS3 whereas lower expression of CURS1 and CURS2. However, opposite pattern was observed in a high curcumin yielding cultivar, GNT-2, where DCS and CURS3 expressions were lower but CURS1 and CURS2 expressions were higher. CURS3 showed similar expression between both cultivars. CURS1 and CURS2 expression patterns showed more closer association than DCS and CURS3 gene expression patterns with each other. Differential gene expression patterns could be predictively associated with differential curcuminoids concentrations in turmeric cultivars.


2020 ◽  
Author(s):  
Timothy J. Durham ◽  
Riza M. Daza ◽  
Louis Gevirtzman ◽  
Darren A. Cusanovich ◽  
William Stafford Noble ◽  
...  

AbstractRecently developed single cell technologies allow researchers to characterize cell states at ever greater resolution and scale. C. elegans is a particularly tractable system for studying development, and recent single cell RNA-seq studies characterized the gene expression patterns for nearly every cell type in the embryo and at the second larval stage (L2). Gene expression patterns are useful for learning about gene function and give insight into the biochemical state of different cell types; however, in order to understand these cell types, we must also determine how these gene expression levels are regulated. We present the first single cell ATAC-seq study in C. elegans. We collected data in L2 larvae to match the available single cell RNA-seq data set, and we identify tissue-specific chromatin accessibility patterns that align well with existing data, including the L2 single cell RNA-seq results. Using a novel implementation of the latent Dirichlet allocation algorithm, we leverage the single-cell resolution of the sci-ATAC-seq data to identify accessible loci at the level of individual cell types, providing new maps of putative cell type-specific gene regulatory sites, with promise for better understanding of cellular differentiation and gene regulation in the worm.


Author(s):  
Jacques Serizay ◽  
Yan Dong ◽  
Jürgen Jänes ◽  
Michael Chesney ◽  
Chiara Cerrato ◽  
...  

AbstractDespite increasingly detailed knowledge of gene expression patterns, the regulatory architectures that drive them are not well understood. To address this, we compared transcriptional and regulatory element activities across five adult tissues of C. elegans, covering ∼90% of cells, and defined regulatory grammars associated with ubiquitous, germline and somatic tissue-specific gene expression patterns. We find architectural features that distinguish two major promoter types. Germline-specific and ubiquitously-active promoters have well positioned +1 and −1 nucleosomes associated with a periodic 10-bp WW signal. Somatic tissue-specific promoters lack these features, have wider nucleosome depleted regions, and are more enriched for core promoter elements, which surprisingly differ between tissues. A 10-bp periodic WW signal is also associated with +1 nucleosomes of ubiquitous promoters in fly and zebrafish but is not detected in mouse and human. Our results demonstrate fundamental differences in regulatory architectures of germline-active and somatic tissue-specific genes and provide a key resource for future studies.


2021 ◽  
Author(s):  
Meng-Ying Lin ◽  
Urte Schlueter ◽  
Benjamin Stich ◽  
Andreas P.M. Weber

Altered transcript abundances and cell specific gene expression patterns that are caused by regulatory divergence play an important role in the evolution of C4 photosynthesis. How these altered gene expression patterns are achieved and whether they are driven by cis- or trans-regulatory changes is mostly unknown. To address this question, we investigated the regulatory divergence between C3 and C3-C4 intermediates, using allele specific gene expression (ASE) analyses of Moricandia arvensis (C3-C4), M. moricandioides (C3) and their interspecific F1 hybrids. ASE analysis on SNP-level showed similar relative proportions of regulatory effects among hybrids: 36% and 6% of SNPs were controlled by cis-only and trans-only changes, respectively. GO terms associated with metabolic processes and the positioning of chloroplast in cells were abundant in transcripts with cis-SNPs shared by all studied hybrids. Transcripts with cis-specificity expressed bias toward the allele from the C3-C4 intermediate genotype. Additionally, ASE evaluated on transcript-level indicated that ~27% of transcripts show signals of ASE in Moricandia hybrids. Promoter-GUS assays on selected genes revealed altered spatial gene expression patterns, which likely result from regulatory divergence in their promoter regions. Assessing ASE in Moricandia interspecific hybrids contributes to the understanding of early evolutionary steps towards C4 photosynthesis and highlights the impact and importance of altered transcriptional regulations in this process.


2014 ◽  
Author(s):  
Michael Kuhn ◽  
Andreas Beyer

Following the increase in available sequenced genomes, tissue-specific transcriptomes are being determined for a rapidly growing number of highly diverse species. Traditionally, only the transcriptomes of related species with equivalent tissues have been compared. Such an analysis is much more challenging over larger evolutionary distances when complementary tissues cannot readily be defined. Here, we present a method for the cross-species mapping of tissue-specific and developmental gene expression patterns across a wide range of animals, including many non-model species. Our approach maps gene expression patterns between species without requiring the definition of homologous tissues. With the help of this mapping, gene expression patterns can be compared even across distantly related species. In our survey of 36 datasets across 27 species, we detected conserved expression programs on all taxonomic levels, both within animals and between the animals and their closest unicellular relatives, the choanoflagellates. We found that the rate of change in tissue expression patterns is a property of gene families. Our findings open new avenues of study for the comparison and transfer of knowledge between different species.


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