The Basics of Molecular Biology

188 Pages·2022·9.562 MB·English

by  Alexander Vologodskii

Alexander Vologodskii
The Basics
of Molecular
Biology
The Basics of Molecular Biology
Alexander Vologodskii
The Basics of Molecular
Biology
Alexander Vologodskii
New York University
New York, NY, USA
ISBN 978-3-031-19403-0 ISBN 978-3-031-19404-7 (eBook)
https://doi.org/10.1007/978-3-031-19404-7
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Preface
This book represents an attempt to describe the major features of life in a very short
volume. It is addressed to people who have an education in areas different from
biology and who want to receive some ideas about the world of molecular and cell
biology. The book assumes a certain knowledge of physics, chemistry, and mathe-
matics that corresponds to the level of high school. The primary attention is paid
here to the most fundamental features of life. The book also briefly considers the
developing areas of biology, which are especially important for medicine and the
future of humankind.
Recommended Literature
There are many excellent textbooks on molecular and cell biology which describe
the subject in detail. Three of these popular titles are shown below. Two other refer-
ences are covering new fast-growing topics related to human genetics.
1. Alberts B, Heald R, Johnson A et al. (2022). Molecular biology of the cell. 7th
ed. New York, NY: Norton & Company.
2. Watson J, Baker T, Bell S et al. (2013). Molecular biology of the gene. 7th ed.
Menlo Park, CA: Benjamin Cummings.
3. Zlatanova J & van Holde K (2015). Molecular Biology: Structure and Dynamics
of Genomes and Proteomes. New York, NY: Garland Science.
4. Reich D (2018). Who we are and how we got here. Ancient DNA and the new
science of the human past. New York, NY: Pantheon Books.
5. Plomin R. (2019). Blueprint: How DNA Makes Us Who We Are. Cambridge,
MA: The MIT Press.
New York, NY, USA Alexander Vologodskii
v
Introduction
We do not know how life appeared on our planet. However, we do know a lot about
the organization of this life, and the goal of this book is to give a brief outline of its
major features. Among natural sciences, biology stays apart from physics and
chemistry in one very important respect. We can deduce, at least qualitatively, prop-
erties of physical objects from the small number of the basic laws of physics. We
can predict the motion of planets around the Sun, the magnetic field around electric
current, the way light passes through the lens, and so on. Although it is technically
difficult to deduce the properties of atoms and molecules from the laws of quantum
mechanics, we are confident that this is possible in principle. Biology is different.
There is no way to deduce the way of life from general principles. There is an enor-
mous amount of specific complex problems that have to be solved by living organ-
isms, and these problems have many different solutions. Although each of these
solutions has to follow the laws of physics and chemistry, it is impractical to search
for all possible solutions to a particular problem in the biological world. Life could
happen in many different ways. We, however, want to know the way of life on our
planet, the one very special choice of many possibilities. To learn about this way, we
have to study life experimentally. It makes the task more difficult. However, the
evolution of life always had certain logic behind it, and finding this logic greatly
helps in the study. We will try to articulate this logic through this book.
Although we cannot deduce much knowledge about life from the general laws of
physics and chemistry, we are confident that life follows these laws. This belief will
be at the base of the book. Analyzing basic processes of life, we will try to consider
them as physical phenomena, wherever such consideration is useful.
Complexity is not the only striking feature of life. It is also incredibly diverse.
Indeed, trees do not resemble animals, and animals seem to have little in common
with bacteria. We know today, however, that the most fundamental features of all
living organisms are nearly identical. All living organisms consist of cells. Some of
them, like animals, have many trillions of cells in their bodies, while others consist
of a single cell. But in all cases, the cell represents a unit of life. It has all the neces-
sary elements for self-reproduction, and new cells can be only formed by the divi-
sion of the existing cells. All basic elements involved in cell reproduction are
vii
viii Introduction
essentially identical in all organisms living on our planet. Through all living organ-
isms, hereditary information is kept in DNA molecules (molecules of deoxyribo-
nucleic acid), and this information is coded in the same way! The same intracellular
mechanisms are used to read this information and to use it for cell growth and repro-
duction. And all cells use the same mechanism for another major process, duplica-
tion of the hereditary information before the cell division. All cells are fundamentally
similar inside, regardless of the striking difference in their appearances. These fun-
damental features of life clearly manifest that all living cells originate from a single
colony that somehow emerged on Earth more than 3 billion years ago.
Acknowledgments
I would like to thank my friends Anshel Gorokhovsky and Igor Kulikov, and my
sister Elena Vologodskaia for their remarks and suggestions which helped me
greatly in preparing this book.
ix
Contents
1 The Major Processes in the Biological World . . . . . . . . . . . . . . . . . . . . 1
1.1 Cells as Basic Units of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Important Facts from Chemistry and Physics . . . . . . . . . . . . . . . . . 2
1.2.1 The Flexibility of Polymer Chains . . . . . . . . . . . . . . . . . . . . 2
1.2.2 Noncovalent Interactions Between Atoms . . . . . . . . . . . . . . 3
1.3 Structure of DNA and Inheritance of Genetic Information . . . . . . . 5
1.3.1 The General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3.2 Chemical Structure of DNA . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3.3 The Double Helix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.4 RNA Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.5 Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.5.1 The General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.5.2 Structure of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.6 Genetic Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.7 From DNA to Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.8 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2 Enzymes, Conformational Changes, Energy,
and Molecular Motors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1 The Motion of Macromolecules in Water . . . . . . . . . . . . . . . . . . . . 23
2.2 Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3 Conformational Flexibility of Proteins and Allosteric
Transitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.4 The Energy in Cell Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.5 Molecular Motors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.6 Energy Transfer from Food to ATP . . . . . . . . . . . . . . . . . . . . . . . . . 34
3 The Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.1 The Lipid Membrane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.2 Membrane Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
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3.2.1 General View . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.2.2 Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.2.3 Osmotic Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.2.4 Transporters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
3.3 Prokaryotic and Eukaryotic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3.4 The Cell Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4 Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.1 Preliminary Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2 Prokaryotic Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.3 Eukaryotic Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.3.1 RNA Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
4.3.2 Mobile Genetic Elements . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
4.4 Chromosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.4.1 General Features of Eukaryotic Chromosomes . . . . . . . . . . 55
4.4.2 Nucleosomes and Epigenetic Inheritance . . . . . . . . . . . . . . 56
4.4.3 Higher Orders of Chromatin Structure . . . . . . . . . . . . . . . . 58
4.5 DNA Sequencing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
4.6 Genome Editing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
4.6.1 Plasmids and Genetic Engineering . . . . . . . . . . . . . . . . . . . 61
4.6.2 CRISPR-Cas9 and Editing of Large Genomes . . . . . . . . . . 63
5 Regulation of Gene Expression and Protein Activity. . . . . . . . . . . . . . 67
5.1 Regulation of Transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
5.1.1 Transcription Regulation in Prokaryotes . . . . . . . . . . . . . . . 68
5.1.2 Eukaryotic Transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
5.1.3 Cell Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
5.2 Posttranscriptional Changes of mRNAs . . . . . . . . . . . . . . . . . . . . . 76
5.2.1 Degradation of mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
5.2.2 Alternative RNA Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . 76
5.2.3 Editing of mRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
5.3 Suppression of Gene Expression by Small
Noncoding RNA Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
6 DNA Replication, Its Fidelity, Mutations, and Repair . . . . . . . . . . . . 81
6.1 Replication of the Double Helix . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
6.1.1 Directionality and Proofreading of DNA Synthesis . . . . . . 81
6.1.2 Replication of Leading and Lagging Strands. . . . . . . . . . . . 83
6.1.3 Telomeres and the Organism Aging . . . . . . . . . . . . . . . . . . . 85
6.1.4 Replication Complex and Epigenetic Inheritance . . . . . . . . 85
6.2 DNA Damage and Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
6.3 Evolution of Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
6.3.1 The Theory of Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
6.3.2 The Evolution Tree . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
6.3.3 Conserved Regions of Eukaryotic Genomes . . . . . . . . . . . . 91
6.3.4 Genomes and the Human History . . . . . . . . . . . . . . . . . . . . 92