Introducing Epigenetics E-Book

Cath Ennis

• Herausgeber: Icon Books
• Kategorie: Wissenschaft und neue Technologien
• Serie: Introducing...
• Sprache: Englisch

Seitenzahl: 119

Veröffentlichungsjahr: 2017

Beschreibung

Epigenetics is the most exciting field in biology today, developing our understanding of how and why we inherit certain traits, develop diseases and age, and evolve as a species.   This non-fiction comic book introduces us to genetics, cell biology and the fascinating science of epigenetics, which is rapidly filling in the gaps in our knowledge, allowing us to make huge advances in medicine. We'll look at what identical twins can teach us about the epigenetic effects of our environment and experiences, why certain genes are 'switched on' or off at various stages of embryonic development, and how scientists have reversed the specialization of cells to clone frogs from a single gut cell.   In Introducing Epigenetics, Cath Ennis and Oliver Pugh pull apart the double helix, examining how the epigenetic building blocks and messengers that interpret and edit our genes help to make us, well, us.

Leseprobe

Published by Icon Books Ltd, Omnibus Business Centre, 39–41 North Road, London N7 9DP Email: [email protected]

ISBN: 978-184831-903-5

Text copyright © 2017 Icon Books Ltd

Illustrations copyright © 2017 Icon Books Ltd

The author and illustrator have asserted their moral rights

Editor: Kiera Jamison

No part of this book may be reproduced in any form, or by any means, without prior permission in writing from the publisher.

Contents

Cover

Title Page

Copyright

Genes, RNA and Proteins

Chromosomes, Nucleosomes and Chromatin

DNA Replication and Mitosis

Meiosis and Inheritance

Beyond the DNA Sequence: Gene Regulation

Nature and Nurture

Twin Studies

The History of Epigenetics

The Modern Understanding of Epigenetic Modifications

DNA Methylation

Histone Modifications

Chromatin Remodelling

Nuclear Location

RNA

Interactions Between Different Epigenetic Modifications

Epigenetics Explains What Genetics Alone Cannot

Epigenetic Changes During Embryonic Development

X Chromosome Inactivation

How Our Environment Affects Our Genes

Not So Identical Twins

Epigenetic Inheritance

Epigenetic Inheritance in Animal Models

Human Epigenetic Inheritance: The Dutch Hunger Winter

Human Epigenetic Inheritance: Överkalix

Mechanisms of Epigenetic Inheritance

Epigenetics in Evolution

Epigenetics in Disease: Ageing

Epigenetics in Disease: Inherited Mutations in Epigenetic Regulators

Epigenetics in Disease: Imprinting Errors

The Epigenetics of Cancer

Epigenetics in Medicine

Stem Cell Therapies

Epigenetics and Pseudoscience

The Future of Epigenetics

Epigenomics

New Epigenetic Modifications

The Epitranscriptome

Epigenetic Editing

Epigen-Ethics

Looking Ahead

Glossary

Recommended Further Reading

Author’s Acknowledgements

Genes, RNA and Proteins

Epigenetics is about how the genes* we inherit from our parents are controlled, and how they interact with our environment: how our genes make us, well, us.

“Epi-” means upon, or in addition; epigenetics is the study of how additional factors interact with genes to direct the processes that make our cells* and bodies work.

Scientists have known about some of these factors for decades, but have only quite recently begun putting everything together to start explaining some of the gaps in our knowledge of genetics. From how embryos develop to how species evolve, from basic laboratory research to drug development – epigenetics is becoming a hot topic of conversation!

UNDERSTANDING EPIGENETICS – HOW OUR GENES INTERACT WITH OUR ENVIRONMENT AND OTHER FACTORS – IS CRUCIAL TO UNDERSTANDING MANY ASPECTS OF BIOLOGY.

* Words marked with an asterisk are defined in the glossary.

To understand epigenetics, we first need to know some basic genetics.

Genes are made of deoxyribonucleic acid (DNA)*. DNA consists of long strings of four component molecules*, called bases*: A, C, G and T. The order, or sequence, of these bases along the string serves as our genetic code.

Two long strings of DNA coil around each other to form the famous double helix structure. The bases on one strand form connections with the bases on the other strand; these connected pairs are the “rungs” in the twisted ladder-like structure of the helix. A always connects to T, and C always connects to G.

CONNECTIONS BETWEEN MATCHING, OR “COMPLEMENTARY”, BASES ON OPPOSITE STRANDS OF DNA – A-T AND C-G – HOLD THE STRUCTURE OF THE DOUBLE HELIX TOGETHER.

The first step in translating the DNA’s coded instructions is called transcription*. Part of the helix opens up, and the bases on one strand connect to new matching (“complementary”) base molecules. The new bases link together into a strand of ribonucleic acid (RNA)*. RNA is similar to DNA, but its short, single strands are less stable and more mobile than the DNA’s long double helix.

Some types of RNA can squeeze out through tiny holes in the membrane that surrounds the cell nucleus*. DNA is too big to get through, so these RNA molecules act as coded messages from the genes to the rest of the cell.

THE DNA'S CODE IS COPIED, OR “TRANSCRIBED”, INTO A STRAND OF RNA, WHICH PASSES THE MESSAGE ON TO THE REST OF THE CELL.

Some of the RNAs that leave the nucleus are called messenger RNAs (mRNAs)*. mRNAs are copies of those sections of the DNA that code for large molecules called proteins*.

Proteins are extremely important. There are thousands of different types, each with a specific function. Many proteins help to control the chemical reactions that keep our cells alive and healthy. For example, proteins are needed to open up the DNA double helix and to join individual bases together into RNA strands during transcription. Other proteins are involved in digesting food, fighting infections, carrying oxygen around the body, and thousands of other diverse functions.

HEY, PANCREAS CELL, MY BOSS GENE NEEDS YOU TO MAKE SOME MORE INSULIN!

The process of converting mRNA sequences into proteins is called translation*.

Each three-base unit – called a “codon”* – of mRNA connects to a transfer RNA (tRNA)* strand that has three complementary bases at one end. The other end is attached to a molecule called an amino acid*. There are different types of amino acid, and each type can only attach to tRNAs that match specific codons.

Just as bases are the building blocks of DNA and RNA, amino acids are the building blocks of proteins. As tRNAs connect to their matching codons along an mRNA strand, their amino acids join up in the same order.

CCC, MEET PROLINE. PROLINE, THIS IS CCC.

The sequence of amino acids in each protein is specified by the sequence of codons in the corresponding mRNA, which in turn matches the sequence of bases in the DNA. The very specific relationship between a given mRNA codon and its matching tRNA molecule, which is only ever attached to a single type of amino acid, is essential to the conversion of the DNA’s code into proteins.

The sequence of amino acids in a protein determines its function. As we saw before, protein functions are essential for life. This is why DNA is so important – it contains all the instructions needed to make our cells and bodies work.

I FIGHT INFECTIONS! I MAKE MRNAS! I CONTROL IT ALL!

Chromosomes, Nucleosomes and Chromatin

Our complete DNA sequence is called our genome*. All humans have extremely similar genomes, although we each have a slightly different version of the sequence. Almost every cell in your body contains its own copy of your unique version of the human genome.

The human genome is divided into 23 sections called chromosomes*. Chromosomes come in pairs: we each inherit one chromosome of each pair from our mother, and the other from our father. The longest human chromosome contains about 2,600 protein-coding genes; the smallest, just 140. Genes are separated by stretches of non-protein-coding DNA.

THERE ARE TWO STRANDS OF DNA PER DOUBLE HELIX, AND ONE DOUBLE HELIX PER CHROMOSOME. THERE ARE 23 CHROMOSOMES FROM EACH PARENT, SO 46 CHROMOSOMES PER CELL. WHICH MEANS 92 STRANDS OF DNA PER CELL!

There are about 21,000 protein-coding genes in the human genome, which contains 3 billion individual bases (A, C, G and T). Laid out end-to-end, the DNA contained in a single cell would be about 1.8 metres (five feet) long. The DNA has to be twisted, folded and compacted to fit into a tiny cell nucleus.

The double helix first wraps around a cluster of eight small proteins called histones*, which bind very tightly to DNA. Each individual unit of eight histone proteins plus DNA is called a nucleosome*. The nucleosomes that assemble along a stretch of DNA look like beads on a string.

EACH NUCLEOSOME “BEAD” CONSISTS OF 8 HISTONE PROTEINS – 2 EACH OF 4 DIFFERENT TYPES OF HISTONE – AND 146 BASES OF DNA.

Four types of histone protein make up the nucleosome beads. A fifth type of histone protein attaches to the linker DNA between nucleosomes, and also to the histones inside each adjacent nucleosome. These connections compact the “beads on a string” into a thicker strand. Additional proteins, called scaffolds, bind to this strand and loop, fold and bend it into even denser structures.

The combination of DNA, histones and scaffold proteins, plus other proteins and RNAs that bind to the overall structure, is called chromatin*.

The density of the chromatin varies along the length of each chromosome. You can actually see this variation in photographs of dyed cells – chromosomes are stripy, with the darker bands corresponding to regions of denser chromatin.

HISTONES AND OTHER PROTEINS HELP TO COMPACT THE DNA INTO INCREASINGLY DENSE STRUCTURES.

DNA Replication and Mitosis

New cells are constantly being created in our bodies, via a process called cell division*.

Before a cell can divide in two, it has to make a second copy of its genome. This DNA replication process happens in a similar way to RNA transcription. The double helix opens up, breaking the connections between the two strands. The bases on each strand reconnect to complementary new partners, which link together into new strands of DNA.

The result at the end of the process is two double helices, each comprising one old strand of DNA from the original cell, and one newly formed strand.

ALL SPIN WITH NEW PARTNERS!

Most cell divisions are of the type called mitosis*, a process that creates two new cells which each have the same number of chromosomes as the original cell.

The chromosomes enter mitosis all jumbled up together like a bowl of spaghetti. As mitosis begins, they separate, condense and form pairs with their newly replicated copies. Fibres then extend out from opposite ends of the cell. Each chromosome attaches to a single fibre. As the fibres contract, one partner from each pair of chromosomes is pulled to each end of the cell. The cell membrane then pinches in at the middle to form two new cells, each surrounded by its own membrane.

I’LL MISS YOU WHEN I’M IN MY NEW CELL! I’LL NEVER FORGET YOU!

Meiosis and Inheritance

Egg and sperm cells are created via a specialized form of cell division called meiosis*. Meiosis involves two rounds of chromosome separation and cell division after DNA replication. Each of the four new cells created during a single meiosis event therefore receives 23 chromosomes, rather than the 23 pairs of chromosomes found in most other cells.

At conception, one egg and one sperm fuse to form a single cell. The 23 chromosomes inherited from each parent pair back up in this fertilized zygote*, so that each new generation starts life with the same amount of DNA as its parents.

WE'RE DIVIDING AGAIN? YES. WE’RE GONNA BE SPERM CELLS! WE ONLY NEED ONE OF EACH CHROMOSOME! THE EGG CELL WILL PROVIDE A MATCHING SET!

As chromosomes pair up for the first meiotic cell division, they swap segments of DNA with their partners. This genetic recombination* occurs when a chromosome breaks, and one of the two broken strands forms a double helix with the complementary sequence on the intact partner chromosome. The second intact strand is displaced by this intruder, and pairs instead with the other broken strand. Any gaps get filled in, and the pieces get stitched back together in their new locations. No information is lost – it’s just remixed. The second round of meiotic cell division starts immediately after the first; no further recombination occurs.

HERE COMES THAT CRAZY CHROMOSOME REMIX! BUT I WON’T DROP THE BASE!

The number and locations of the chromosome breaks that trigger recombination are essentially random, so different pieces of DNA are swapped every time. This is why every sperm and egg cell is unique: they all get some of their DNA from each of the parent’s two chromosomes, but in different combinations.

Unique eggs and sperm create unique offspring. You don’t look exactly like your parents because their genetic material was shuffled before it was dealt to you; you don’t look exactly like your siblings because their shuffle was different. The exception, identical twins, come from a single fertilized zygote that splits in two.

After conception, the fertilized zygote divides by mitosis to create all the different types of cells it will need as it matures into an embryo. This wonderfully intricate and complex process requires the zygote’s genes to be transcribed and translated in carefully coordinated ways.

Twentieth-century biologists learned a lot about how this developmental process works, especially after the structure of DNA was characterized in 1953 by Watson, Crick, Wilkins and Franklin. However, as they put the pieces of the puzzle together, they also identified some gaps. Clearly, there are aspects of genetics that can’t be explained by studying gene sequences alone.

I THINK I SHOULD HAVE STUDIED SOMETHING EASIER, LIKE QUANTUM PHYSICS.

Beyond the DNA Sequence: Gene Regulation

The human body comprises hundreds of different types of cell. Each type has specialized functions, mediated by its unique combination of proteins. Some proteins are produced in every cell; others are abundant in some cell types and present at low levels – or completely absent – in others.

The process by which the original fertilized zygote produces all of the body’s cell types is called cell differentiation*. Some cells differentiate as they undergo mitosis, becoming progressively more specialized, while others (called stem cells*) stay in a less specialized, more versatile state. The cell’s combination of proteins changes as it differentiates.

I’M GOING TO MAKE A BABY! CUE CELL DIVISION! TIME TO START EXPERIMENTING WITH NEW PROTEIN COMBINATIONS … HOORAY FOR CELL DIFFERENTIATION!

Normal cell differentiation is a one-way process that converts versatile stem cells into more specialized mature cells. This ensures that mature brain cells, for example, don’t spontaneously revert to being stem cells and start filling the skull with bone or muscle!

In 1962, John Gurdon (b. 1933) became the first scientist to artificially reverse cell differentiation. He took the nucleus of a fully differentiated tadpole gut cell and transferred it into a frog’s egg from which the nucleus had been removed. The cloned egg matured into a new, healthy frog. This experiment proved that fully differentiated cells retain all the genetic material needed to produce every cell in the body.

A WHOLE, HEALTHY FROG, CLONED FROM A SINGLE MATURE GUT CELL! CELL DIFFERENTIATION CAN BE REVERSED! I COULD KISS YOU!

Gurdon’s work disproved an earlier hypothesis that cells gradually discard unnecessary pieces of DNA as they differentiate, leaving behind only the genes they need to carry out their specialized functions. Modern science has since confirmed that with a few exceptions (some blood cells are weird), every cell in the human body contains exactly the same DNA as the original fertilized zygote. However, different cells transcribe and translate different parts of the genome, and it wasn’t clear at the time how the same DNA sequence could be used to produce such diverse combinations of RNAs and proteins in different cell types.