Genomes and Their Organization PDF

Genomes and their organization All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Lecture overview Eukaryotic...

Genomes and their organization All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Lecture overview Eukaryotic chromosomes Organelles with their own genomes Eukaryotic MGEs Viruses and virus-like elements Genomes = nuclear genome (chromosomes) + organellar genomes + MGEs All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Eukaryotes DNA is folded into chromatin DNA double helical structure coils round histones. DNA bound to histones forms NUCLEOSOMES (10nm FIBRES) DNA wound around histone protein octamers (each histone consist of eight proteins) This structure is often compared to thread wrapped around a spool All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer. All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Histones x2 5 Canonical histones H1/H5, H2A, H2B, H3, and H4 Octamer core H2A, H2B, H3, and H4 α helices + loops Net + charge Yao Z, Chen Y, Cao W, Shyh‐Chang N. Chromatin ‐ modifying drugs and metabolites in cell fate control. Cell Proliferation. 2020 Nov;53(11):e12898. All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Histones 5 Canonical histones H1/H5, H2A, H2B, H3, and H4 Linker H1/H5 Determines nucleosomal repeat length Stabilize chromatin Fyodorov, D., Zhou, BR., Skoultchi, A. et al. Emerging roles of linker histones in regulating chromatin structure and function. Nat Rev Mol Cell Biol 19, 192–206 (2018). https://doi.org/10.1038/nrm.2017.94 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Histones’ interactions with DNA Mainly use positively charged amino acids (Arg and Lys) for electrostatic interactions with negative DNA Can be post-translationally modified Affects replication, transcription, and repair processes E.g., positively charged lysine forms salt bridge with negatively charged DNA backbone => stability Lysine acetylation results in lower binding affinity => less stability ~ 150 bp wound around core octamer structure = nucleosome Linker histone bound ~ 10 bp of DNA at entry and exit points of nucleosome = chromatosome Fyodorov, D., Zhou, BR., Skoultchi, A. et al. Emerging roles of linker histones in regulating chromatin structure and function. Nat Rev Mol Cell Biol 19, 192–206 (2018). https://doi.org/10.1038/nrm.2017.94 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  The 10-nm chromatin fibre Initially thought to only be observed to be present in localized areas of the chromosome => not the default state of chromatin Recent evidence suggest that 10- nm fibre may be bulk packaged in a disordered “polymer-melt” state Hansen JC, Connolly M, McDonald CJ, Pan A, Pryamkova A, Would allow fibres to constantly Ray K, Seidel E, Tamura S, Rogge R, Maeshima K. The 10-nm chromatin fiber and its relationship to interphase chromosome move around and be rearranged organization. Biochemical Society Transactions. 2018 Feb 19;46(1):67-76. All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  The 30-nm chromatin fibre 10-nm fibre coiled upon itself to form a helical chromatin fibre Solenoid helix or zigzag helix? Six nucleosomes (chromatosomes?) compacted into a single helix turn Typically thought to be the default state, but several experiments have led to no 30-nm fibres being observed in vivo Do they even exist in vivo? Maeshima K, Hihara S, Eltsov M. Chromatin structure: does the 30-nm fibre exist in vivo?. Current opinion in cell biology. 2010 Jun 1;22(3):291-7. All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Looped domains Also called topologically associated domains Poorly understood and still actively studied Seems to be conserved structures over generations Related to co-regulation of expression in certain areas of the genome? Associated with different expression patterns, e.g., tissue types? Dixon JR, Gorkin DU, Ren B. Chromatin domains: the unit of chromosome organization. Molecular cell. 2016 Jun 2;62(5):668-80. All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Chromosomes Condensing through Topoisomerase II and condensin complex Usually multiple pairs of linear chromosomes Located inside cell nucleus Autosomes and allosomes Interphase results in looser packaging => access for transcription Metaphase results in tighter packaging Each chromatid is a double-stranded DNA double helix Sister chromatids joined with centromere All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Chromosome numbers Differ drastically Not necessarily associated with complexity of organism All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Organellar genomes Primary endosymbiosis Early Asgardarchaeon in close association (syntrophy) with early alphaproteobacterium Genomes look similar to those organisms from which they were derived Vosseberg, J., van Hooff, J.J.E., Köstlbacher, S. et al. The emerging view on the origin and early evolution of eukaryotic cells. Nature 633, 295–305 (2024). https://doi.org/10.1038/s41586-024- 07677-6 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Organellar genomes Mitochondria Evidence suggest it was derived Amorim A, Fernandes T, Taveira N. Mitochondrial from an early alphaproteobacterium DNA in human identification: a review. PeerJ. 2019 Aug Symbionts undergo genome 13;7:e7314. reductions Many genes transferred to proto- eukaryote nuclear genome Usually single dsDNA, circular Need some precursors encoded on nuclear genome ~15 to 60 kbp Vosseberg, J., van Hooff, J.J.E., Köstlbacher, S. et al. The emerging view on the origin and early evolution of eukaryotic cells. Nature 633, 295–305 (2024). https://doi.org/10.1038/s41586-024-07677-6 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Organellar genomes Chloroplasts Likely from an early cyanobacterium Similar to mitochondria – genome reductions Single, dsDNA, circular molecule Some precursors encoded in nuclear genome Usually encode 120-130 genes Photosynthesis, transcription, translation Range in size (110-220 kbp) Daniell, H., Lin, CS., Yu, M. et al. Chloroplast genomes: diversity, evolution, and applications in genetic engineering. Genome Biol 17, 134 (2016). https://doi.org/10.1186/s13059-016-1004-2 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Eukaryotic plasmids Mainly found in fungi, algae, and higher plants Origins unclear and poorly understood Some at least derived from prokaryotic plasmids Plasmid genes often found in organellar genomes and vice versa Lee, J., Kim, K., Yang, E. et al. Reconstructing the complex evolutionary history of mobile plasmids in red algal genomes. Sci Rep 6, 23744 (2016). https://doi.org/10.1038/srep23744 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Eukaryotic viruses Six established realms of viruses – only no known eukaryotic Adnaviria currently No known eukaryotic Adnaviria yet Eugene V Koonin, Jens H Kuhn, Valerian V Dolja, Mart Krupovic, Megataxonomy and global ecology of the virosphere, The ISME Journal, Volume 18, Issue 1, January 2024, wrad042, https://doi.org/10.1093/ismejo/wrad042 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  dsDNA dsDNA ssDNA and dsDNA dsDNA in A-form ssRNA (+ or -), dsRNA, and dsDNA - ssRNA Eugene V Koonin, Jens H Kuhn, Valerian V Dolja, Mart Krupovic, Megataxonomy and global ecology of the virosphere, The ISME Journal, Volume 18, Issue 1, January 2024, wrad042, https://doi.org/10.1093/ismejo/wrad042 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  How are viruses and plasmids related? Viruses and plasmids are vessels of cargo genes that facilitate HGT Some recent evidence suggest that numerous ssDNA viruses could be derived from plasmids? Kazlauskas, D., Varsani, A., Koonin, E.V. et al. Multiple origins of prokaryotic and eukaryotic single-stranded DNA viruses from bacterial and archaeal plasmids. Nat Commun 10, 3425 (2019). https://doi.org/10.1038/s41467-019-11433-0 All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Example of eukaryotic genome architecture: Marchantia polymorpha Ohyama K, Takemura M, Oda K, 8 Autosomes + 1 allosome Fukuzawa H, Kohchi T, Nakayama S, Ishizaki K, Fujisawa M, Yamato K. Gene content, organization and molecular evolution of plant Mitochondrial genome organellar genomes and sex chromosomes—insights from the case of the liverwort Marchantia Chloroplast genome polymorpha. Proceedings of the Japan Academy, Series B. 2009 Mar 30;85(3):108-24. ⃰ Can house plasmid for transformation Diop SI, Subotic O, Giraldo‐Fonseca A, Waller M, Kirbis A, Neubauer A, Potente G, Murray‐Watson R, Boskovic F, Bont Z, Hock Z. A pseudomolecule‐scale genome assembly of the liverwort Marchantia polymorpha. The Plant Journal. 2020 Seo, D.H., Kim, S., Seo, H.J. et al. A Simple Protocol for Thallus Culture-Based Genetic Mar;101(6):1378-96. Transformation of the Liverwort Marchantia polymorpha. J. Plant Biol. 65, 11–19 (2022). https://doi.org/10.1007/s12374-021-09339-w All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.  Quick lecture recap Eukaryotic DNA has complex DNA Mitochondria and chloroplasts are condensing processes organelles that possess their own Several histones with different structures and genomes functions are present Rampant transfer of genes between Unclear whether 10 nm or 30 nm fibres are organelles and nuclear genomes dominant/naturally occurring during evolution Looped domains of chromatin fibres still Eukaryotic plasmids derived from poorly understood prokaryotic plasmids Could be associated with co-regulated regions on the genome Many different eukaryotic viruses Further condensation leads to chromosomes Some ssDNA viruses derived from plasmids? All course content is copyrighted and remains the intellectual property of Dr. Marike Palmer. Please do not distribute this material without the express permission of Dr. Marike Palmer.