Landmark papers from the past 60 years

Landmark papers from the past 60 years

Since the discovery of the structure of DNA in the middle of the last century, the study of the genetic code has undergone enormous technical and conceptual developments. The Max Planck Institute for Molecular Genetics has led many of these developments. On the occasion of the institute’s 60th anniversary, we take a look at the key discoveries at the institute that shaped our understanding of the intricacies of the genetic code, its regulation, and its implications for human development, individuality, and disease.


Research Epochs

Viruses and Bacteria (1965-1995)
Ribosomes (1964-1990)
DNA methylation and epigenetics (1965-2000, 2017- now)
Human genetics (1994 - now)
High throughput genomics and computational biology (1994 - now)
Gene regulation, 3D genome and cancer (1964 - now)
Non-Mendelian inheritance (2003 - now )

Viruses and Bacteria (1965-1995)


The relationship between molecular structure and transformation efficiency of some S. aureus plasmids isolated from B. subtilis. Canosi U, Morelli G, Trautner TA. Molecular & General Genetics (1978)

10.1007/bf00267617                                                          PDF Download

The paper reported an unusual observation that concatemerized DNA is more efficient in transforming bacteria, and provided important clues for the design and use of modern plasmids as DNA cloning vectors.

     Labs: Thomas Trautner

Ribosomes (1964-1990)


Ribosomal proteins. VII. Two-dimensional polyacrylamide gel electrophoresis for fingerprinting of ribosomal proteins. Kaltschmidt E, Wittmann HG. Analytical Biochemistry (1970)                   PDF Download

The paper reported the an almost complete separation of ribosomal proteins by 2D gel electrophoresis, which represented a major breakthrough for the sequencing and identification of ribosomal proteins.

     Labs: Heinz-Günther Wittmann


Total reconstitution of functionally active 50S ribosomal subunits from Escherichia coli. Nierhaus KH, Dohme F. Proceedings of the National Academy of Sciences (1974)                               PDF Download

Reported the first in vitro assembly of the entire catalytically active large ribosomal subunit (50S) from purified E. coli components (33 proteins, 2 rRNAs). This spurred an entire domain of biochemical and structural research built on the ability to assemble the ribosome in a test tube.

     Labs: Knud Nierhaus


Three tRNA binding sites on Escherichia coli ribosomes. Rheinberger HJ, Sternbach H, Nierhaus KH. Proceedings of the National Academy of Sciences (1981)                                  PDF Download

An important paper for the mapping and identification of catalytic and regulatory sites on ribosomes.    

     Labs: Knud Nierhaus


A tunnel in the large ribosomal subunit revealed by three-dimensional image reconstruction. Yonath A, Leonard KR, Wittmann HG. Science (1987)                               PDF Download

A landmark paper that describes one of the first Cryo-EM structures of the ribosome with implications for our understanding of translational control.

     Labs: Heinz-Günther Wittmann


The Highly Conserved LepA Is a Ribosomal Elongation Factor that Back-Translocates the Ribosome. Qin Y, Polacek N, Vesper O, ... Wilson DN, Nierhaus KH. Cell (2006)

10.1016/j.cell.2006.09.037                                                  PDF Download

An important paper for the mapping and identification of catalytic and regulatory sites on ribosomes.

     Labs: Knud Nierhaus

DNA methylation and epigenetics (1965-2000, 2017 - now)


A gene essential for de novo methylation and development in ascobolus reveals a novel type of eukaryotic DNA methyltransferase structure. Malagnac F, Wendel B, Goyon C, ... Trautner TA, Walter J. Cell (1997)

10.1016/s0092-8674(00)80410-9                                     PDF Download

One of the first ever reports of cytosine DNA methylation having a function role in gene control and development of a model fungus.

     Labs: Thomas Trautner


'Pseudo' domains in phage-encoded DNA methyltransferases. Lange C, Jugel A, Walter J, Noyer-Weidner M & Trautner TA. Nature (1991)

10.1038/352645a0                                                               PDF Download

The paper reported the discovery of an accessory domain that plays a role in the genomic recruitment and function of a DNA-methyltransferase.

     Labs: Thomas Trautner


TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers. Charlton J, Jung EJ, Mattei AL, Bailly N, Liao J, Martin EJ, Giesselmann P, Brändl B, Stamenova, EK Müller FJ, Kiskinis E, Gnirke A, Smith ZD, Meissner A. Nature Genetics (2020)

10.1038/s41588-020-0639-9                                             PDF Download                                      Press Release

The paper provided importance evidence for a model that local competition between DNA-methyltransferases and TET methylcytosine dioxygenases controls DNA methylation levels in mammalian cells.

     Labs: Alexander Meissner


Epigenetic regulator function through mouse gastrulation. Grosswendt S, Kretzmer H, Smith ZD, Kumar AS, Hetzel S, Wittler L, Klages S, Timmermann B, Mukherji S, Meissner A. Nature (2020)

10.1038/s41586-020-2552-x                                              PDF Download                                    Press Release

The paper reported single cell resolution maps of mouse embryos that lack specific DNA-modifying enzymes and epigenetic regulators.

     Labs: Alexander Meissner

Human genetics (1994 - now)


Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE. Cell (1997)

10.1016/s0092-8674(00)80514-0                                      PDF Download

One of the original studies that reported protein aggregation as the potential underlying cause of Huntington’s disease, the first disease linked to a specific genetic variant in humans.

     Labs: Erich Wanker, Hans Lehrach


Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Najmabadi H, Motazacker MM, Garshasbi M, Kahrizi K, Tzschach A, Chen W, Behjati F, Hadavi V, Nieh SE, Abedini SS, Vazifehmand R, Firouzabadi SG, Jamali P, Falah M, Seifati SM, Grüters A, Lenzner S, Jensen LR, Rüschendorf F, Kuss AW, Ropers HH. Human Genetics (2006)

10.1007/s00439-006-0292-0                                               PDF Download

This paper was the starting point for systematic studies to identify the underlying genetic cause of autosomal recessive intellectual disability.

     Labs: Hans-Hilger Ropers


Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Ullmann R, Turner G, Kirchhoff M, Chen W, Tonge B, Rosenberg C, Field M, Vianna-Morgante AM, Christie L, Krepischi-Santos AC, Banna L, Brereton AV, Hill A, Bisgaard AM, Müller I, Hultschig C, Erdogan F, Wieczorek G, Ropers HH. Human Mutation (2007)

10.1002/humu.20546                                                            PDF Download

One of the first studies that established the high-resolution array Comparative Genome Hybridization (array CGH) technology, which for the following decade became as essential tool to detect small submicroscopic deletions and duplications everywhere in the genome.

      Labs: Hans-Hilger Ropers


Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, O'Donovan MC, Erdogan F, Owen MJ, Ropers HH, Ullmann R. Human Molecular Genetics. 2008

10.1093/hmg/ddm323                                                            PDF Download

A key study reporting a link between genomic copy number variants and schizophrenia.

Labs: Hans-Hilger Ropers


A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Tarpey P.S, Smith R, Pleasance E, ... Futreal P.A, Stratton M.R. Nature Genetics (2009)

10.1038/ng.367                                                                      PDF Download

The paper reported on a large consortium effort to map the genetic components of mental retardation in humans.

     Labs: Hans-Hilger Ropers


Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Najmabadi H, Hu H, Garshasbi M, ...Kahrizi K, Ropers H.H. Nature (2011)

10.1038/nature10423                                                           PDF Download

The paper reported the discovery of genetic variants thar are associated with cognitive disorders.

     Labs: Hans-Hilger Ropers


X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Hu H, Haas S.A, Chelly J, ... Ropers H.-H, Kalscheuer V.M. Molecular Psychiatry (2016)

10.1038/mp.2014.193                                                          PDF Download

The paper reported genetic variants associated with intellectual disability.

     Labs: Hans-Hilger Ropers, Vera Kalscheuer

High throughput genomics and computational biology (1994 - now)


The DNA sequence of human chromosome 21. Hattori M, Fujiyama A, Taylor T.D, ...Reinhardt R, Yaspo M.-L. Nature (2000)

10.1038/35012518                                                                PDF Download

A large consortium effort, co-ordinated by the MPI-MG, that reported the second complete sequence of an entire human chromosome.

     Labs: Marie-Laure Yaspo, Hans Lehrach

A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Sultan M, Schulz M.H, Richard H, ...Lehrach H, Yaspo M.-L. Science (2008)

10.1126/science.1160342                                                    PDF Download

One of the first ever use of RNA-Sequencing technology for the assembly of entire transcriptomes, including splice isoforms.

     Labs: Marie-Laure Yaspo, Hans Lehrach, Martin Vingron, Stefan Haas

ConsensusPathDB--a database for integrating human functional interaction networks. Kamburov A, Wierling C, Lehrach H, Herwig H. Nucleic Acids Research (2009)

10.1093/nar/gkn698                                                              PDF Download

One of the first databases that annotated functional gene-gene interactions on a genome-wide scale in humans.

     Labs: Ralf Herwig, Hans Lehrach

Histone modification levels are predictive for gene expression. Karlić R, Chung H, Lasserre J, Vlahovicek K, Vingron M. Proceeding of the National Academy of Sciences (2010)

10.1073/pnas.0909344107                                                   PDF Download

Stereotypic histone modifications decorate genes and non-coding cis-elements. This paper is one of the first reports demonstrating that such epigenetic marks predict the activity of genes.

     Labs: Martin Vingron

A global reference for human genetic variation. The 1000 Genomes Project Consortium. Nature (2015)

10.1038/nature15393                                                            PDF Download

The MPIMG has played an important role in the 1000 Genomes Project that aimed to describe common genetic variants in humans.

     Labs: Marie-Laure Yaspo, Hans Lehrach, Ralf Herwig

Gene regulation, 3D genome, and cancer (1964 - now)


Multiple repressor binding sites in the genome of bacteriophage P1. Velleman M, Dreiseikelmann B, Schuster H. Proceedings of the National Academy of Sciences (1987)

10.1073/pnas.84.16.5570                                                    PDF Download

The paper reported that multiple repressor binding sites in the phage P1 are necessary its activity, which is one of the first examples of combinatorial gene control.

     Labs: Heinz Schuster

The c4 repressors of bacteriophages P1 and P7 are antisense RNAs. Citron M, Schuster H. Cell (1990)

10.1016/0092-8674(90)90023-8                                         PDF Download

The paper reported the discovery that a repressive trans-factor in bacteriophages is in anti-sense RNA. It is one of the first ever reports on a non-coding RNA with regulatory function.

     Labs: Heinz Schuster

Serine- and threonine-specific protein kinase activities of purified gag-mil and gag-raf proteins. Moelling K, Heimann B, Beimling P, Rapp UR, Sander T. Nature (1984)

10.1038/312558a0                                                               PDF Download

A landmark discovery that the viral B-raf oncogene encodes a protein kinase with specific activity on serines and threonines. This paper played a key role in the realization that cancer can be caused by deregulated kinase pathways.

     Labs: Karin Mölling

A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A. Developmental Cell (2001)

10.1016/s1534-5807(01)00085-5                                        PDF Download

This paper reported provided compelling evidence that gene activity and lifespan in nematodes is controlled through nuclear hormonal signaling.

     Labs: Adam Antebi

The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Macura K, Bläss G, Kellis M, Werber M, Herrmann BG. Developmental Cell (2013)

10.1016/j.devcel.2012.12.012                                              PDF Download

This paper demonstrated that a long non-coding RNA (lncRNA) acts as an essential regulator of organogenesis. One of the first reports on a lncRNA with in vivo function.

     Labs: Bernhard Herrmann

Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R, Santos-Simarro F, Gilbert-Dussardier B, Wittler L, Borschiwer M, Haas SA, Osterwalder M, Franke M, Timmermann B, Hecht J, Spielmann M, Visel A, Mundlos S. Cell (2015)

10.1016/j.cell.2015.04.004                                                    PDF Download

This landmark study provided for the first time experimental evidence that the rearrangement of the 3D organization of the genome disrupts enhancer-promoter interactions, dysregulates genes, and causes genetic disease.

     Labs: Stefan Mundlos


Formation of new chromatin domains determines pathogenicity of genomic duplications. Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V, Schöpflin R, Kraft K, Kempfer R, Jerković I, Chan WL, Spielmann M, Timmermann B, Wittler L, Kurth I, Cambiaso P, Zuffardi O, Houge G, Lambie L, Brancati F, Pombo A, Vingron M, Spitz F, Mundlos S. Nature (2016)

10.1038/nature19800                                                            PDF Download

This paper reported astonishing examples how disease-associated DNA variants variant create new topological domains in mammalian genomes.

     Labs: Stefan Mundlos, Martin Vingron

Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites. Veenvliet JV, Bolondi A, Kretzmer H, Haut L, Scholze-Wittler M, Schifferl D, Koch F, Guignard L, Sampath Kumar A, Pustet A, Heimann S, Buschow R, Wittler L, Timmermann B, Meissner A, Herrmann BG. Science (2020)

10.1126/science.aba4937                                                    PDF Download                                     Press Release

This paper reported trunk-like structures (TLS), organoids derived from embryonic stem cells that recapitulate development of the trunk of a mouse embryo.

     Labs: Bernhard Herrmann, Alexander Meissner

Non-Mendelian inheritance (2003 - now)


The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice. Bauer H, Willert J, Koschorz B, Herrmann BG. Nature Genetics (2005)

10.1038/ng1617                                                                     PDF Download

One of the first reports that identified as gene linked to non-Mendelian inheritance by the mouse T/t complex, called “transmission ratio distortion”.

     Labs: Bernhard Herrmann

Retention of gene products in syncytial spermatids promotes non-Mendelian inheritance as revealed by the t complex responder. Véron N, Bauer H, Weiße AY, Lüder G, Werber M, Herrmann BG. Genes & Development (2009)

10.1101/gad.553009                                                             PDF Download

This paper provided key evidence that the pathway controlling non-Mendelian inheritance is operational in in syncytial spermatids in mice.

     Labs: Bernhard Herrmann




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