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A new hypothesis to explain disease dominance. 一个解释疾病优势的新假说。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-03-01 Epub Date: 2025-01-08 DOI: 10.1016/j.tig.2024.11.009
Brian Juvik, Lara Falcucci, Pia R Lundegaard, Didier Y R Stainier
{"title":"A new hypothesis to explain disease dominance.","authors":"Brian Juvik, Lara Falcucci, Pia R Lundegaard, Didier Y R Stainier","doi":"10.1016/j.tig.2024.11.009","DOIUrl":"10.1016/j.tig.2024.11.009","url":null,"abstract":"<p><p>The onset and progression of dominant diseases are thought to result from haploinsufficiency or dominant negative effects. Here, we propose transcriptional adaptation (TA), a newly identified response to mRNA decay, as an additional cause of some dominant diseases. TA modulates the expression of so-called adapting genes, likely via mRNA decay products, resulting in genetic compensation or a worsening of the phenotype. Recent studies have challenged the current concepts of haploinsufficiency or poison proteins as the mechanisms underlying certain dominant diseases, including Brugada syndrome, hypertrophic cardiomyopathy, and frontotemporal lobar degeneration. We hypothesize that for these and other dominant diseases, when the underlying mutation leads to mRNA decay, the phenotype is due at least partly to the dysregulation of gene expression via TA.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"187-193"},"PeriodicalIF":13.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958929","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
Advances in euglenoid genomics: unravelling the fascinating biology of a complex clade. 曙光基因组学的进展：揭开一个复杂支系迷人的生物学面纱。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-03-01 Epub Date: 2024-08-14 DOI: 10.1016/j.tig.2024.07.007
Oskar Fields, Michael J Hammond, Xiao Xu, Ellis C O'Neill
{"title":"Advances in euglenoid genomics: unravelling the fascinating biology of a complex clade.","authors":"Oskar Fields, Michael J Hammond, Xiao Xu, Ellis C O'Neill","doi":"10.1016/j.tig.2024.07.007","DOIUrl":"10.1016/j.tig.2024.07.007","url":null,"abstract":"<p><p>Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"251-260"},"PeriodicalIF":13.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989529","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 ABCs of the H2Bs: The histone H2B sequences, variants, and modifications.
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-20 DOI: 10.1016/j.tig.2025.01.003
Anna J Voss, Erica Korb
{"title":"The ABCs of the H2Bs: The histone H2B sequences, variants, and modifications.","authors":"Anna J Voss, Erica Korb","doi":"10.1016/j.tig.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.tig.2025.01.003","url":null,"abstract":"<p><p>Histone proteins are the building blocks of chromatin, and function by wrapping DNA into complex structures that control gene expression. Histone proteins are regulated by post-translational modifications (PTMs) and by histone variant exchange. In this review, we will provide an overview of one of these histones: H2B. We will first define the sequences of human and mouse H2B proteins and discuss potential designations for canonical H2B. We will also describe the differential functions of H2B variants compared with canonical H2B. Finally, we will summarize known H2B modifications and their functions in regulating transcription. Through review of H2B genes, proteins, variants, and modifications, we aim to highlight the importance of H2B for epigenetic and transcriptional regulation of the cell.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473214","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
Transposon-host arms race: a saga of genome evolution.
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-19 DOI: 10.1016/j.tig.2025.01.009
Yuka W Iwasaki, Keisuke Shoji, Shinichi Nakagwa, Tomoichiro Miyoshi, Yukihide Tomari
{"title":"Transposon-host arms race: a saga of genome evolution.","authors":"Yuka W Iwasaki, Keisuke Shoji, Shinichi Nakagwa, Tomoichiro Miyoshi, Yukihide Tomari","doi":"10.1016/j.tig.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.tig.2025.01.009","url":null,"abstract":"<p><p>Once considered 'junk DNA,' transposons or transposable elements (TEs) are now recognized as key drivers of genome evolution, contributing to genetic diversity, gene regulation, and species diversification. However, their ability to move within the genome poses a potential threat to genome integrity, promoting the evolution of robust host defense systems such as Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KRAB-ZFPs), the human silencing hub (HUSH) complex, 4.5SH RNAs, and PIWI-interacting RNAs (piRNAs). This ongoing evolutionary arms race between TEs and host defenses continuously reshapes genome architecture and function. This review outlines various host defense mechanisms and explores the dynamic coevolution of TEs and host defenses in animals, highlighting how the defense mechanisms not only safeguard the host genomes but also drive genetic innovation through the arms race.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470015","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
Empowering continuous evolution of proteins by in vivo mutagenesis.
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-11 DOI: 10.1016/j.tig.2025.01.007
Zhanzhi Liu, Jing Wu
{"title":"Empowering continuous evolution of proteins by in vivo mutagenesis.","authors":"Zhanzhi Liu, Jing Wu","doi":"10.1016/j.tig.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.tig.2025.01.007","url":null,"abstract":"<p><p>In vivo mutagenesis enriches genetic polymorphism within cells, which is pivotal for triggering continuous evolution. Remarkable strides have been made in this field. Here, we summarize the current in vivo mutagenesis methods focusing on the theme of mutation range and provide an outlook on their future directions, offering inspiration to relevant researchers.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411462","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 Genomic Code: the genome instantiates a generative model of the organism.
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-10 DOI: 10.1016/j.tig.2025.01.008
Kevin J Mitchell, Nick Cheney
{"title":"The Genomic Code: the genome instantiates a generative model of the organism.","authors":"Kevin J Mitchell, Nick Cheney","doi":"10.1016/j.tig.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.tig.2025.01.008","url":null,"abstract":"<p><p>How does the genome encode the form of the organism? What is the nature of this genomic code? Inspired by recent work in machine learning and neuroscience, we propose that the genome encodes a generative model of the organism. In this scheme, by analogy with variational autoencoders (VAEs), the genome comprises a connectionist network, embodying a compressed space of 'latent variables', with weights that get encoded by the learning algorithm of evolution and decoded through the processes of development. The generative model analogy accounts for the complex, distributed genetic architecture of most traits and the emergent robustness and evolvability of developmental processes, while also offering a conception that lends itself to formalization.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400890","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
Mitochondrial-derived microproteins: from discovery to function. 线粒体来源的微蛋白：从发现到功能。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-01 Epub Date: 2024-12-16 DOI: 10.1016/j.tig.2024.11.010
Kelvin Yen, Brendan Miller, Hiroshi Kumagai, Ana Silverstein, Pinchas Cohen
{"title":"Mitochondrial-derived microproteins: from discovery to function.","authors":"Kelvin Yen, Brendan Miller, Hiroshi Kumagai, Ana Silverstein, Pinchas Cohen","doi":"10.1016/j.tig.2024.11.010","DOIUrl":"10.1016/j.tig.2024.11.010","url":null,"abstract":"<p><p>Given the uniqueness of the mitochondria, and the fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery of an increasing number of microproteins from this organelle and the importance of mitochondria to cellular and organismal health make it a priority to study this novel class of proteins in search of possible therapeutic targets and cures. In this review, we discuss the history of MDP discovery, describe the function of each MDP, and conclude with future goals and techniques to help discover more MDPs.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"132-145"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the world of small proteins in plant biology and bioengineering. 探索植物生物学和生物工程中的小蛋白质世界。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-14 DOI: 10.1016/j.tig.2024.09.004
Louise Petri, Anne Van Humbeeck, Huanying Niu, Casper Ter Waarbeek, Ashleigh Edwards, Maurizio Junior Chiurazzi, Ylenia Vittozzi, Stephan Wenkel
{"title":"Exploring the world of small proteins in plant biology and bioengineering.","authors":"Louise Petri, Anne Van Humbeeck, Huanying Niu, Casper Ter Waarbeek, Ashleigh Edwards, Maurizio Junior Chiurazzi, Ylenia Vittozzi, Stephan Wenkel","doi":"10.1016/j.tig.2024.09.004","DOIUrl":"10.1016/j.tig.2024.09.004","url":null,"abstract":"<p><p>Small proteins are ubiquitous in all kingdoms of life. MicroProteins, initially characterized as small proteins with protein interaction domains that enable them to interact with larger multidomain proteins, frequently modulate the function of these proteins. The study of these small proteins has contributed to a greater comprehension of protein regulation. In addition to sequence homology, sequence-divergent small proteins have the potential to function as microProtein mimics, binding to structurally related proteins. Moreover, a multitude of other small proteins encoded by short open reading frames (sORFs) and peptides, derived from diverse sources such as long noncoding RNAs (lncRNAs) and miRNAs, contribute to a variety of biological processes. The potential of small proteins is evident, offering promising avenues for bioengineering that could revolutionize crop performance and reduce reliance on agrochemicals in future agriculture.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"170-180"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481007","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
Finding functional microproteins. 寻找功能性微蛋白。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1016/j.tig.2024.12.001
Sikandar Azam, Feiyue Yang, Xuebing Wu
{"title":"Finding functional microproteins.","authors":"Sikandar Azam, Feiyue Yang, Xuebing Wu","doi":"10.1016/j.tig.2024.12.001","DOIUrl":"10.1016/j.tig.2024.12.001","url":null,"abstract":"<p><p>Genome-wide translational profiling has uncovered the synthesis in human cells of thousands of microproteins, a class of proteins traditionally overlooked in functional studies. Although an increasing number of these microproteins have been found to play critical roles in cellular processes, the functional relevance of the majority remains poorly understood. Studying these low-abundance, often unstable proteins is further complicated by the challenge of disentangling their functions from the noncoding roles of the associated DNA, RNA, and the act of translation. This review highlights recent advances in functional genomics that have led to the discovery of >1000 human microproteins required for optimal cell proliferation. Ongoing technological innovations will continue to clarify the roles and mechanisms of microproteins in both normal physiology and disease, potentially opening new avenues for therapeutic exploration.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"107-118"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cis to trans: small ORF functions emerging through evolution. 从顺式到反式：进化过程中出现的小型 ORF 功能。
IF 13.6 2区 生物学
Trends in Genetics Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tig.2024.10.012
Casimiro Baena-Angulo, Ana Isabel Platero, Juan Pablo Couso
{"title":"Cis to trans: small ORF functions emerging through evolution.","authors":"Casimiro Baena-Angulo, Ana Isabel Platero, Juan Pablo Couso","doi":"10.1016/j.tig.2024.10.012","DOIUrl":"10.1016/j.tig.2024.10.012","url":null,"abstract":"<p><p>Hundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5' leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated, while characterised smORF functions have risen from anecdotal to identifiable trends: smORFs can either have a cis-noncoding regulatory function (involving low translation of nonfunctional peptides) or full coding function mediated by robustly translated peptides, often having cellular and physiological roles as membrane-associated regulators of canonical proteins. The evolutionary context reveals that many smORFs represent new genes emerging de novo from noncoding sequences. We suggest a mechanism for this process, where cis-noncoding smORF functions provide niches for the subsequent evolution of full peptide functions.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"119-131"},"PeriodicalIF":13.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741061","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
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