Genome research最新文献_第10页

Characterization of DNA methylation reader proteins of Arabidopsis thaliana 拟南芥DNA甲基化解读蛋白的研究

IF 7 2区生物学

Genome research Pub Date : 2024-12-04 DOI: 10.1101/gr.279379.124

Jonathan Cahn, James P.B. Lloyd, Ino D. Karemaker, Pascal W.T.C. Jansen, Jahnvi Pflueger, Owen Duncan, Jakob Petereit, Ozren Bogdanovic, A. Harvey Millar, Michiel Vermeulen, Ryan Lister

{"title":"Characterization of DNA methylation reader proteins of Arabidopsis thaliana","authors":"Jonathan Cahn, James P.B. Lloyd, Ino D. Karemaker, Pascal W.T.C. Jansen, Jahnvi Pflueger, Owen Duncan, Jakob Petereit, Ozren Bogdanovic, A. Harvey Millar, Michiel Vermeulen, Ryan Lister","doi":"10.1101/gr.279379.124","DOIUrl":"https://doi.org/10.1101/gr.279379.124","url":null,"abstract":"In plants, cytosine DNA methylation (mC) is largely associated with transcriptional repression of transposable elements, but it can also be found in the body of expressed genes, referred to as gene body methylation (gbM). gbM is correlated with ubiquitously expressed genes; however, its function, or absence thereof, is highly debated. The different outputs that mC can have raise questions as to how it is interpreted—or read—differently in these sequence and genomic contexts. To screen for potential mC-binding proteins, we performed an unbiased DNA affinity pull-down assay combined with quantitative mass spectrometry using methylated DNA probes for each DNA sequence context. All mC readers known to date preferentially bind to the methylated probes, along with a range of new mC-binding protein candidates. Functional characterization of these mC readers, focused on the MBD and SUVH families, was undertaken by ChIP-seq mapping of genome-wide binding sites, their protein interactors, and the impact of high-order mutations on transcriptomic and epigenomic profiles. Together, these results highlight specific context preferences for these proteins, and in particular the ability of MBD2 to bind predominantly to gbM. This comprehensive analysis of Arabidopsis mC readers emphasizes the complexity and interconnectivity between DNA methylation and chromatin remodeling processes in plants.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"28 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts 利用PlatinumCRISPr进行结构优化的sgRNA选择，实现Cas9基因敲除的高效产生

IF 7 2区生物学

Genome research Pub Date : 2024-12-03 DOI: 10.1101/gr.279479.124

Irmgard U. Haussmann, Thomas C. Dix, David W.J. McQuarrie, Veronica Dezi, Abdullah I. Hans, Roland Arnold, Matthias Soller

{"title":"Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts","authors":"Irmgard U. Haussmann, Thomas C. Dix, David W.J. McQuarrie, Veronica Dezi, Abdullah I. Hans, Roland Arnold, Matthias Soller","doi":"10.1101/gr.279479.124","DOIUrl":"https://doi.org/10.1101/gr.279479.124","url":null,"abstract":"A single guide RNA (sgRNA) directs Cas9 nuclease for gene-specific scission of double-stranded DNA. High Cas9 activity is essential for efficient gene editing to generate gene deletions and gene replacements by homologous recombination. However, cleavage efficiency is below 50% for more than half of randomly selected sgRNA sequences in human cell culture screens or model organisms. We used in vitro assays to determine intrinsic molecular parameters for maximal sgRNA activity including correct folding of sgRNAs and Cas9 structural information. From the comparison of over 10 data sets, we find major constraints in sgRNA design originating from defective secondary structure of the sgRNA, sequence context of the seed region, GC context, and detrimental motifs, but we also find considerable variation among different prediction tools when applied to different data sets. To aid selection of efficient sgRNAs, we developed web-based PlatinumCRISPr, an sgRNA design tool to evaluate base-pairing and sequence composition parameters for optimal design of highly efficient sgRNAs for Cas9 genome editing. We applied this tool to select sgRNAs to efficiently generate gene deletions in Drosophila Ythdc1 and Ythdf, that bind to N6 methylated adenosines (m6A) in mRNA. However, we discovered that generating small deletions with sgRNAs and Cas9 leads to ectopic reinsertion of the deleted DNA fragment elsewhere in the genome. These insertions can be removed by standard genetic recombination and chromosome exchange. These new insights into sgRNA design and the mechanisms of CRISPR–Cas9 genome editing advance the efficient use of this technique for safer applications in humans.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"2 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The rate and spectrum of new mutations in mice inferred by long-read sequencing 通过长读测序推断小鼠新突变的速率和谱

IF 7 2区生物学

Genome research Pub Date : 2024-12-02 DOI: 10.1101/gr.279982.124

Eugenio López-Cortegano, Jobran Chebib, Anika Jonas, Anastasia Vock, Sven Künzel, Peter D. Keightley, Diethard Tautz

{"title":"The rate and spectrum of new mutations in mice inferred by long-read sequencing","authors":"Eugenio López-Cortegano, Jobran Chebib, Anika Jonas, Anastasia Vock, Sven Künzel, Peter D. Keightley, Diethard Tautz","doi":"10.1101/gr.279982.124","DOIUrl":"https://doi.org/10.1101/gr.279982.124","url":null,"abstract":"All forms of genetic variation originate from new mutations, making it crucial to understand their rates and mechanisms. Here, we use long-read PacBio sequencing to investigate de novo mutations that accumulated in 12 inbred mouse lines derived from three commonly used inbred strains (C3H, C57BL/6, and FVB) maintained for 8-15 generations in a mutation accumulation (MA) experiment. We built chromosome-level genome assemblies based on the MA line founders' genomes, and then employed a combination of read and assembly-based methods to call the complete spectrum of new mutations. On average, there are ~45 mutations per haploid genome per generation, about half of which (54%) are insertions and deletions shorter than 50 bp (indels). The remainder are single nucleotide mutations (SNMs, 44%) and large structural mutations (SMs, 2%). We found that the degree of DNA repetitiveness is positively correlated with SNM and indel rates, and that a substantial fraction of SMs can be explained by homology-dependent mechanisms associated with repeat sequences. Most (90%) indels can be attributed to microsatellite contractions and expansions, and there is a marked bias towards 4 bp indels. Among the different types of SMs, tandem repeat mutations have the highest mutation rate, followed by insertions of transposable elements (TEs). We uncover a rich landscape of active TEs, and notable differences in their spectrum among MA lines and strains, and a high rate of gene retroposition. Our study offers novel insights into mammalian genome evolution, and highlights the importance of repetitive elements in shaping genomic diversity.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"45 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inferring disease progressive stages in single-cell transcriptomics using a weakly-supervised deep learning approach 使用弱监督深度学习方法推断单细胞转录组学中的疾病进展阶段

IF 7 2区生物学

Genome research Pub Date : 2024-12-02 DOI: 10.1101/gr.278812.123

Fabien Wehbe, Levi Adams, Jordan Babadoudou, Samantha Yuen, Yoon-Seong Kim, Yoshiaki Tanaka

引用次数: 0

A low-abundance class of Dicer-dependent siRNAs produced from a variety of features in C. elegans 一种低丰度的dicer依赖性sirna，由秀丽隐杆线虫的多种特征产生

IF 7 2区生物学

Genome research Pub Date : 2024-12-02 DOI: 10.1101/gr.279083.124

Thiago L. Knittel, Brooke E. Montgomery, Alex J. Tate, Ennis W. Deihl, Anastasia S. Nawrocki, Frederic J. Hoerndli, Taiowa A. Montgomery

{"title":"A low-abundance class of Dicer-dependent siRNAs produced from a variety of features in C. elegans","authors":"Thiago L. Knittel, Brooke E. Montgomery, Alex J. Tate, Ennis W. Deihl, Anastasia S. Nawrocki, Frederic J. Hoerndli, Taiowa A. Montgomery","doi":"10.1101/gr.279083.124","DOIUrl":"https://doi.org/10.1101/gr.279083.124","url":null,"abstract":"Canonical small interfering RNAs (siRNAs) are processed from double-stranded RNA (dsRNA) by Dicer and associate with Argonautes to direct RNA silencing. In Caenorhabditis elegans, 22G-RNAs and 26G-RNAs are often referred to as siRNAs but display distinct characteristics. For example, 22G-RNAs do not originate from dsRNA and do not depend on Dicer, whereas 26G-RNAs require Dicer but derive from an atypical RNA duplex and are produced exclusively antisense to their messenger RNA (mRNA) templates. To identify canonical siRNAs in C. elegans, we first characterized the siRNAs produced via the exogenous RNA interference (RNAi) pathway. During RNAi, dsRNA is processed into ∼23 nt duplexes with ∼2 nt, 3′-overhangs, ultimately yielding siRNAs devoid of 5′G-containing sequences that bind with high affinity to the Argonaute RDE-1, but also to the microRNA (miRNA) pathway Argonaute, ALG-1. Using these characteristics, we searched for their endogenous counterparts and identified thousands of endogenous loci representing dozens of unique elements that give rise to mostly low to moderate levels of siRNAs, called 23H-RNAs. These loci include repetitive elements, putative coding genes, pseudogenes, noncoding RNAs, and unannotated features, many of which adopt hairpin (hp) structures reminiscent of the hpRNA/RNAi pathway in flies and mice. RDE-1 competes with other Argonautes for binding to 23H-RNAs. When RDE-1 is depleted, these siRNAs are enriched in ALG-1 and ALG-2 complexes. Our results expand the known repertoire of C. elegans small RNAs and their Argonaute interactors, and demonstrate that key features of the endogenous siRNA pathway are relatively unchanged in animals.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"45 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression 单核CUT&RUN阐明了内在和基因组学驱动的表观遗传异质性在头颈癌进展中的作用

IF 7 2区生物学

Genome research Pub Date : 2024-12-02 DOI: 10.1101/gr.279105.124

Howard Womersley, Daniel Muliaditan, Ramanuj DasGupta, Lih Feng Cheow

{"title":"Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression","authors":"Howard Womersley, Daniel Muliaditan, Ramanuj DasGupta, Lih Feng Cheow","doi":"10.1101/gr.279105.124","DOIUrl":"https://doi.org/10.1101/gr.279105.124","url":null,"abstract":"Interrogating regulatory epigenetic alterations during tumor progression at the resolution of single cells has remained an understudied area of research. Here we developed a highly sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in isogenic primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived tumor cell lines. We find that the epigenome can be involved in diverse modes to contribute towards HNSCC progression. First, we demonstrate that gene expression changes during HNSCC progression can be comodulated by alterations in both copy number and chromatin activity, driving epigenetic rewiring of cell states. Furthermore, intratumour epigenetic heterogeneity (ITeH) may predispose subclonal populations within the primary tumour to adapt to selective pressures and foster the acquisition of malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to the existing toolkit of single-cell epigenomic assays and can be used to dissect the functionality of the epigenome during cancer progression.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"13 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging 嵌合线粒体 RNA 转录本预测线粒体遗传疾病和衰老中的线粒体基因组缺失突变

IF 7 2区生物学

Genome research Pub Date : 2024-11-27 DOI: 10.1101/gr.279072.124

Amy R Vandiver, Allen Herbst, Paul Stothard, Jonathan Wanagat

{"title":"Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging","authors":"Amy R Vandiver, Allen Herbst, Paul Stothard, Jonathan Wanagat","doi":"10.1101/gr.279072.124","DOIUrl":"https://doi.org/10.1101/gr.279072.124","url":null,"abstract":"While it is well understood that mitochondrial DNA (mtDNA) deletion mutations cause incurable diseases and contribute to aging, little is known about the transcriptional products that arise from these DNA structural variants. We hypothesized that mitochondrial genomes containing deletion mutations express chimeric mitochondrial RNAs. To test this, we analyzed human and rat RNA sequencing data to identify, quantitate, and characterize chimeric mitochondrial RNAs. We observed increased chimeric mitochondrial RNA frequency in samples from patients with mitochondrial genetic diseases and in samples from aged humans. The spectrum of chimeric mitochondrial transcripts reflected the known pattern of mtDNA deletion mutations. To test the hypothesis that mtDNA deletions induce chimeric RNA transcripts, we treated 18 mo and 34 mo rats with guanidinopropionic acid to induce high levels of skeletal muscle mtDNA deletion mutations. With mtDNA deletion induction, we demonstrate that the chimeric mitochondrial transcript frequency also increased and correlated strongly with an orthogonal DNA-based mutation assay performed on identical samples. Further, we show that the frequency of chimeric mitochondrial transcripts predicts expression of both nuclear and mitochondrial genes central to mitochondrial function, demonstrating the utility of these events as metrics of age-induced metabolic change. Mapping and quantitation of chimeric mitochondrial RNAs provides an accessible, orthogonal approach to DNA-based mutation assays, offers a potential method for identifying mitochondrial pathology in widely accessible datasets, and opens a new area of study in mitochondrial genetics and transcriptomics.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"25 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A deconvolution framework that uses single-cell sequencing plus a small benchmark dataset for accurate analysis of cell type ratios in complex tissue samples 利用单细胞测序和小型基准数据集精确分析复杂组织样本中细胞类型比例的解卷积框架

IF 7 2区生物学

Genome research Pub Date : 2024-11-25 DOI: 10.1101/gr.278822.123

Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A. Owen, Ivana K. Kim, Ana Aparicio, Sanghoon Lee, Anil K. Sood, Scott Kopetz, John Paul Shen, John N. Weinstein, Margaret M. DeAngelis, Rui Chen, Wenyi Wang

{"title":"A deconvolution framework that uses single-cell sequencing plus a small benchmark dataset for accurate analysis of cell type ratios in complex tissue samples","authors":"Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A. Owen, Ivana K. Kim, Ana Aparicio, Sanghoon Lee, Anil K. Sood, Scott Kopetz, John Paul Shen, John N. Weinstein, Margaret M. DeAngelis, Rui Chen, Wenyi Wang","doi":"10.1101/gr.278822.123","DOIUrl":"https://doi.org/10.1101/gr.278822.123","url":null,"abstract":"Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using this well-matched, i.e., benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using two benchmark datasets of healthy retinas and ovarian cancer tissues suggest much-improved deconvolution accuracy. Leveraging tissue-specific benchmark datasets, we applied DeMixSC to a large cohort of 453 age-related macular degeneration patients and a cohort of 30 ovarian cancer patients with various responses to neoadjuvant chemotherapy. Only DeMixSC successfully unveiled biologically meaningful differences across patient groups, demonstrating its broad applicability in diverse real-world clinical scenarios. Our findings reveal the impact of technological discrepancy on deconvolution performance and underscore the importance of a well-matched dataset to resolve this challenge. The developed DeMixSC framework is generally applicable for accurately deconvolving large cohorts of disease tissues, including cancers, when a well-matched benchmark dataset is available.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"35 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay 哺乳动物宿主和嵌套基因对的全球鉴定揭示了组织特异性转录相互作用

IF 7 2区生物学

Genome research Pub Date : 2024-11-22 DOI: 10.1101/gr.279430.124

Bertille Montibus, James A. Cain, Rocio T. Martinez-Nunez, Rebecca J. Oakey

{"title":"Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay","authors":"Bertille Montibus, James A. Cain, Rocio T. Martinez-Nunez, Rebecca J. Oakey","doi":"10.1101/gr.279430.124","DOIUrl":"https://doi.org/10.1101/gr.279430.124","url":null,"abstract":"Nucleotide sequences along a gene provide instructions to transcriptional and cotranscriptional machinery allowing genome expansion into the transcriptome. Nucleotide sequence can often be shared between two genes and in some occurrences, a gene is located completely within a different gene; these are known as host/nested gene pairs. In these instances, if both genes are transcribed, overlap can result in a transcriptional crosstalk where genes regulate each other. Despite this, a comprehensive annotation of where such genes are located and their expression patterns is lacking. To address this, we provide an up-to-date catalog of host/nested gene pairs in mouse and human, showing that over a tenth of all genes contain a nested gene. We discovered that transcriptional co-occurrence is often tissue specific. This coexpression was especially prevalent within the transcriptionally permissive tissue, testis. We use this developmental system and scRNA-seq analysis to demonstrate that the coexpression of pairs can occur in single cells and transcription in the same place at the same time can enhance the transcript diversity of the host gene. In agreement, host genes are more transcript-diverse than the rest of the transcriptome. Host/nested gene configurations are common in both human and mouse, suggesting that interplay between gene pairs is a feature of the mammalian genome. This highlights the relevance of transcriptional crosstalk between genes which share nucleic acid sequence. The results and analysis are available on an Rshiny application (https://hngeneviewer.sites.er.kcl.ac.uk/hn_viewer/).","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"34 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets 食草动物分子约束的趋同性放松揭示了肝脏和肾脏功能在哺乳动物饮食中不断变化的作用

IF 7 2区生物学

Genome research Pub Date : 2024-11-22 DOI: 10.1101/gr.278930.124

Matthew D. Pollard, Wynn K. Meyer, Emily E. Puckett

{"title":"Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets","authors":"Matthew D. Pollard, Wynn K. Meyer, Emily E. Puckett","doi":"10.1101/gr.278930.124","DOIUrl":"https://doi.org/10.1101/gr.278930.124","url":null,"abstract":"Mammalia comprises a great diversity of diet types and associated adaptations. An understanding of the genomic mechanisms underlying these adaptations may offer insights for improving human health. Comparative genomic studies of diet that employ taxonomically restricted analyses or simplified diet classifications may suffer reduced power to detect molecular convergence associated with diet evolution. Here, we use a quantitative carnivory score—indicative of the amount of animal protein in the diet—for 80 mammalian species to detect significant correlations between the relative evolutionary rates of genes and changes in diet. We have identified six genes—ACADSB, CLDN16, CPB1, PNLIP, SLC13A2, and SLC14A2—that experienced significant changes in evolutionary constraint alongside changes in carnivory score, becoming less constrained in lineages evolving more herbivorous diets. We further consider the biological functions associated with diet evolution and observe that pathways related to amino acid and lipid metabolism, biological oxidation, and small molecule transport experienced reduced purifying selection as lineages became more herbivorous. Liver and kidney functions show similar patterns of constraint with dietary change. Our results indicate that these functions are important for the consumption of animal matter and become less important with the evolution of increasing herbivory. So, genes expressed in these tissues experience a relaxation of evolutionary constraint in more herbivorous lineages.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"5 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0