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As the name states (Stated Clearly Videos)

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As the name states (Stated Clearly Videos)

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https://www.statedclearly.com/videos/

What is DNA? What is a gene? The differences between RNA and DNA are just a few clips worth watching.

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Our animations clarify scientific topics so everyone can understand. Great for use in the classroom and for learning on your own.

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Mind Map of DNA Structure and Replication

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Mind Map of DNA Structure and Replication

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Transgenic Technologies (Helpful Link for IA3)

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Transgenic Technologies (Helpful Link for IA3)

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https://learn.genetics.utah.edu/content/science/

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Genetic Science and Society [Internet]. Salt Lake City (UT): Genetic Science Learning Center; 2013 [cited 2022 Oct 10] Available from https://learn.genetics.utah.edu/content/science/

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https://www.youtube.com/watch?v=gbSIBhFwQ4s

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https://www.genome.gov/genetics-glossary

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Talking Glossary of Genetic Terms | NHGRI

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Use Padlet to support one another during Exam preparation.

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https://pdb101.rcsb.org/learn/flyers-posters-and-calendars/flyer/what-is-a-protein

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Types of Proteins (utah.edu)

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Anatomy of a Gene (utah.edu)

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TIP Start With: Cell Transcription & Translation

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TIP Start With: Cell Transcription & Translation

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https://contrib.pbslearningmedia.org/WGBH/conv20/lsps07-int-celltrans/index.html

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What are Traits? (utah.edu) (2 mins)

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Identical twins have exactly the same DNA, but they are not exactly alike. Each twin has his or her own personality, talents, likes, and dislikes. There are even diseases that appear in one twin but not the other, including arthritis, diabetes, autism, schizophrenia, cancer, and many others. The differences between identical twins don't come from DNA-they all come from external factors.

Scientists often study twins to understand how genes and the environment work together to affect traits. They compare traits in identical twins, who have identical DNA, and fraternal twins, who share half their DNA, just like any siblings. If a characteristic appears more frequently in identical twin pairs than in fraternal twin pairs, then it has an inherited component.

The differences between identical twins don't come from DNA-they all come from external factors.

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Identical twins have exactly the same DNA, but they are not exactly alike. Each twin has his or her own personality, talents, likes, and dislikes. There are even diseases that appear in one twin but not the other, including arthritis, diabetes, autism, schizophrenia, cancer, and many others.

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What are DNA and Genes? (utah.edu) (2 mins)

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The order of building blocks in a strand of DNA makes up a "sequence." We can read a DNA sequence like letters in a book. In fact, we know the sequence of the entire human genome-all 3 billion letters. That's enough information to fill roughly 1,000 200-page books!

Contained within the 3 billion letters of the human genome are about 21,000 genes. Most of our known genes code for proteins, but some code for RNA molecules.

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The order of building blocks in a strand of DNA makes up a "sequence." We can read a DNA sequence like letters in a book. In fact, we know the sequence of the entire human genome-all 3 billion letters. That's enough information to fill roughly 1,000 200-page books!

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What are Chromosomes? (utah.edu) (2 mins)

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Different organisms have different numbers of chromosomes. Organisms that appear more complex do not always have more chromosomes or genes than less-complex ones.

Humans have 23 pairs of chromosomes. The first 22 pairs are called autosomes. The last pair are called sex chromosomes, and they are different between males and females. Most females have two X chromosomes (XX), and most males have an X and a Y (XY).

Most other species have different numbers of chromosome pairs than we do. Species also vary in the number of chromosome sets they have. In some species of bees and ants, males have just one copy of every chromosome (they develop from unfertilized eggs), while females have two. Some species of plants have four or more copies of each chromosome. Bacteria have just a single chromosome, arranged in a ring.

Species also differ in how chromosomes specify sex. In birds, the sex chromosomes are called Z and W. Females are ZW and males are ZZ. The tiny roundworm C. elegans has just one type of sex chromosome called X. Those with one X chromosome (known as XO) become male, and those with two X chromosomes become hermaphrodites, meaning they make both eggs and sperm. The platypus has ten sex chromosomes. Females have five pairs of X chromosomes, and males have five X chromosomes and five Y chromosomes. Some turtles do not use sex chromosomes at all. The sex of a baby turtle depends on how warm it was during a critical period as it developed inside its egg.

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Humans have 23 pairs of chromosomes. The first 22 pairs are called autosomes. The last pair are called sex chromosomes, and they are different between males and females. Most females have two X chromosomes (XX), and most males have an X and a Y (XY).

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Transcribe and Translate a Gene (utah.edu)

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RNA: The Versatile Molecule (utah.edu)

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Even though RNA molecules are made from just 4 simple building blocks, RNA
can take on a variety of shapes and carry out many different functions.

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RNA's Role in the Central Dogma (utah.edu)

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https://www.youtube.com/watch?v=mBq1ULWJp_M

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Beyond the Central Dogma (utah.edu)

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Some RNA molecules can silence specific genes, turning off the production of proteins
that are not needed at a certain place or time. This job is especially important during
development, when cells begin to differentiate into specific types, such as muscle, skin,
and liver. Each cell type needs only…

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PDB-101: Home Page (rcsb.org)

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The brain orchestrates everything we do, sending signals through the nervous system to control different parts of our body. The brain is also the home of our thoughts and consciousness, as neurons process the input from our senses and store what they find as memories. Many drugs are available to help tune the function of the brain and nervous system when there are problems. Unfortunately, the effects of some drugs are hard to control and can lead to abuse and addiction. Explore PDB-101 Resources to learn about proteins related to our nervous system and mental health.

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The brain orchestrates everything we do, sending signals through the nervous system to control different parts of our body. The brain is also the home of our thoughts and consciousness, as neurons process the input from our senses and store what they find as memories.

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Augmented Reality iPhone Application that allows you to explore protein structures within the real environment.

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Paper Transcription & Translation (Practical)

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Paper Transcription & Translation (Practical)

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Basic Genetics (utah.edu)

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This hands-on activity reinforces the processes of transcription and translation. Usingpaper cut-outs, students follow the rules of complementary base pairing to build an mRNAmolecule, then translate the mRNA codons to assemble amino acids, building a protein. At theend, they learn which of 5 actual…

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https://www.genome.gov/about-genomics/teaching-tools/dna-origami

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NHGRI's Jenny Montooth provides a walkthrough of the step-by-step instructions.

NHGRI's Director Eric Green decided to challenge his toughest competitor, Cardboard Eric, to see who could fold our DNA origami the fastest. Take a look to see who won!

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Step-by-step instructions and printable folding paper included in the downloadable document.

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What are Proteins? (utah.edu) (1 min)

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A protein’s three-dimensional shape is uniquely suited to its function. The 20 different amino acid building blocks can be arranged in different ways to form a nearly infinite assortment of protein shapes.

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extension://elhekieabhbkpmcefcoobjddigjcaadp/https://teach.genetics.utah.edu/content/dna/Have-Your-DNA-and-Eat-It-Too.pdf

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extension://elhekieabhbkpmcefcoobjddigjcaadp/https://teach.genetics.utah.edu/content/dna/Reading-DNA.pdf

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(1) What is a Protein? (from PDB-101) - YouTube (7 mins)

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Can you provide a resource that explains Helicase better? or provide an explanation in our next class?

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This is a really good image that shows the difference in structure and nitrogenous bases.

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https://ib.bioninja.com.au/higher-level/topic-7-nucleic-acids/

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https://qcebiologyrevision.com/year12/unit4topic1/

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DNA structure and replication Cellular replication and variation Gene expression Mutations Inheritance Biotechnology

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Image sourced from https://teachmephysiology.com/biochemistry/cell-growth-death/dna-replication/

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https://www.genome.gov/genetics-glossary/Protein

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Your DNA, the Environment, & Epigenetics

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Your DNA, the Environment, & Epigenetics

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https://www.youtube.com/watch?v=ujLppvMqUOI&t=1s (3 mins)

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Your DNA, the Environment, and Epigenetics

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https://www.genome.gov/about-genomics/about-genomics/educational-resources/infographics/Your-Genome-You

# data[].attributes.body
https://dnalc.cshl.edu/resources/animations/

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DNALC animations feature stunning visualizations of cellular and molecular processes. Journey inside a cell as you follow proteins in Cell Signals. Zoom along a three-dimensional rendering of 650,000 nucleotides of human chromosome in Chromosome 11 Flyover. Processes like DNA translation, transcription, replication, and more are explained in interactive animations.

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DNALC animations feature stunning visualizations of cellular and molecular processes. Journey inside a cell as you follow proteins in Cell Signals. Zoom along a three-dimensional rendering of 650,000 nucleotides of human chromosome in Chromosome 11 Flyover. Processes like DNA translation, transcription, replication, and more are explained in interactive animations.

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https://www.biointeractive.org/planning-tools/resource-playlists/teaching-gene-expression-using-genetic-medicine

If you choose the CRISPR option for IA3 please use the interactive media (CRISPR-Cas9 Mechanism & Applications). It explains the process in detail and then interviews scientists that use CRISPR in the lab.

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Teaching Gene Expression Using Genetic Medicine

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This playlist can be used to teach several core topics in genetics and molecular biology by connecting students with case studies and multimedia about genetic medicine. It can be used in AP/IB Biology courses.

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A bit of healthy competition never hurt anyone! 

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Choice: Would you like weekly team quizzes?

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Choice: Would you like weekly team quizzes?

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Class vote YES or NO

- Form a team with 3-4 members
- Create a team name
- Carryout pre-readings & formative quiz will be scheduled each week.
- Formative performance quiz (provide a collective "team" verbal answer and/or individual mini-whiteboards for answers, like a game show).
- Weekly prize to the team that wins.
- The team quizzes can help prepare you for the culminating task which is a written quiz formatted like your external exam.

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https://learn.concord.org/protein-folding

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Interactive simulations and activities for learning about the linear structure of proteins and how they can fold to create more complex three-dimensional structures

Proteins are composed of linear chains of amino acids that are encoded within sequences of nucleotides found in the DNA of an organism. When proteins are needed by a cell, the DNA code is transcribed into messenger RNA (mRNA) molecules within the nucleus. The newly created mRNA molecules resemble the DNA in their nucleotide structure and carry a template of that structure into the cytoplasm where it is translated into the language of amino acids at the cell's ribosome.

Individual amino acids have side chains with varying properties of electrical charge. When suspended in water, chains of amino acids can move, bend, and interact with one another along the chain and with the surrounding environment. Forces of electrical attraction and repulsion cause the chain to eventually settle into a conformation that maximizes the molecule's stability.

Log in to gain access to these supplemental teacher resources!

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Interactive simulations and activities for learning about the linear structure of proteins and how they can fold to create more complex three-dimensional structures Proteins are composed of linear chains of amino acids that are encoded within sequences of nucleotides found in the DNA of an organism.

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Please provide a learning activity that allows us to explore the details of transcription. As I feel you moved through the content too quickly.

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https://www.teaching.unsw.edu.au/group-work
Read about the benefits of Team based learning.
These are just some of the workforce skills that you can develop.

adoption of group roles and responsibilities

negotiation

delegation

leadership

questioning and analysis

creative problem solving

reflection and evaluation

conflict management and resolution

constructive feedback and reflective listening

organisation and time management

group facilitation

(UNSW Sydney, 2023).

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Group Work | UNSW Teaching Staff Gateway

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Overview Group work or cooperative learning is a method of instruction that gets students to work together in groups. Employers value a person’s ability to work cooperatively. Indeed, studies show that they value it more highly than the ability to work independently. This is because, in most contemp…

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https://quizlet.com/au/797572260/biology-chapter-52-flash-cards/

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https://create.kahoot.it/search-results/all?query=Genes&orderBy=relevance#course=6f75df88-e5d8-48d9-8df1-d8a4d8e8f318

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Topoisomerase (5 mins) in DNA Replication

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Topoisomerase (5 mins) in DNA Replication

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https://www.youtube.com/watch?v=wQ5oPL0PqYE

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Untangler of Knots: The Amazing Topoisomerase Molecular Machine

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Each episode is approximately 45 minutes. This series is thought provoking as it explores the ethical boundaries of gene therapy.

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Just a 2 minute taste.

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Unnatural Selection: Season 1 | Main Trailer | Netflix

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Interesting Blog explaining Gene Editing

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Interesting Blog explaining Gene Editing

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https://jibraankadri.medium.com/its-a-prime-time-for-gene-editing-prime-editing-4361a07c6cbe

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https://www.genome.gov/genetics-glossary

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https://www.youtube.com/watch?v=YO244P1e9QM

Carbs: (CHO) made of Carbon, Hydrogen, Oxygen. Polysaccharides made of Monosaccharides (glucose).
Lipids: (CHO) made of Carbon, Hydrogen, Oxygen. Glycerol and fatty acids.
Proteins: (CHON) made of Carbon, Hydrogen, Oxygen, Nitrogen. Polypeptide chain made of amino acids.
Nucleic Acids: (CHONP) made of Carbon, Hydrogen, Oxygen, Nitrogen, Phosphate. Nucleic Acid made of nucleotides.

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https://www.youtube.com/watch?v=6tSIbSKacXA

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https://www.biotopics.co.uk/A15/Monomers_and_polymers.html

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Site author Richard Steane

The BioTopics website gives access to interactive resource material, developed to support the learning and teaching of Biology at a variety of levels.

Your browser does not support this audio format.

Poly- means many -
Mono- means one or single

Polymers are substances made up from many smaller sub-units, chemically joined together.

These smaller sub-units are molecules called monomers.

This diagram represents a number of monomers.

Biological molecules are joined together using a chemical reaction calledcondensation.

This forms a chemical bond between the 2 molecules with the elimination of water, so a molecule of water is produced for each bond. Actually, -H is taken from one side and -OH from the other.

This animation shows a small polymer being built up from six monomers. Tip: keep the mouse pointer off the space above - it resets the display until it is clicked on.

hydro- means water
- lysis means splitting

The opposite process to condensation is hydrolysis, which breaks the bond(s) in the polymer to release smaller molecules (often individual monomers).

This requires a water molecule to split the bond. This adds -H to one side and -OH to the other. This is what happens in digestion.

This animation shows a polymer being broken down into dimers.

Examples of biological monomers and polymers:

Click here to see things differently

Polymers are broken down
by hydrolysis into: Monomers

Poly saccharides

Mono saccharides
(simple sugars)

Polypeptides
and proteins

Amino-acids

Nucleic acids

Nucleotides

The processes of condensation and hydrolysis, and biological molecules are dealt with in different ways on this site:

Condensation and hydrolysis - leading to other webpages with several animations of the processes
Molecular structure of glucose and other carbohydrates - leading to other webpages with 3-D interactive molecules
Amino acid structure - a simple webpage with more mouseover interaction

Other topics in this series (Biological Chemicals)
Carbohydrates - Monosaccharides, disaccharides, polysaccharides
Lipids - Fatty acids, triglycerides, phospholipids
Proteins - Amino acids, polypeptides
Enzymes - Hydrolysis and synthesis of biological chemicals all take place under enzyme control
pH and hydrogen ion concentration [H⁺] - All to do with dissociation of water and resulting ionic concentrations
ATP - The energy currency of the cell
Nucleic acids - Nucleotides, DNA, RNA, and of course Ribose and deoxyribose
DNA replication - Doubling of the double helix
Water - The Biological Significance of Water, and Molecular Explanation
Inorganic ions - Hydrogen, iron, sodium, phosphate

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examples of biological monomers and polymers

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Site author Richard Steane The BioTopics website gives access to interactive resource material, developed to support the learning and teaching of Biology at a variety of levels. Your browser does not support this audio format. Poly- means many - Mono- means one or single Polymers are substances made up from many smaller sub-units, chemically joined together.

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https://www.youtube.com/watch?v=pLdZJAc3bGQ

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Lesson Plan that explains CRISPR (IA3 Resource)

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Lesson Plan that explains CRISPR (IA3 Resource)

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http://pged.org/lesson-plans/#CRISPR

If you chose CRISPR for your Research Investigation please Download the lesson plan and slideshow as it has many links to additional resources.

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The Personal Genetics Education Project raises awareness and sparks conversation about the potential benefits as well as the ethical, legal, and social implications of personal genetics. We strive to be inclusive of all voices in these discussions, regardless of socioeconomic or educational background, cultural or religious affiliation, and ethnic or personal identity.

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https://www.youtube.com/watch?v=FGnS-Xk0ZqU

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https://www.youtube.com/watch?v=YqUjDzcmVFs&t=1s

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Why is DNA right-handed? – with Turi King

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https://www.youtube.com/watch?v=vl6Vlf2thvI

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https://www.youtube.com/watch?v=pv3Kj0UjiLE

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https://www.youtube.com/watch?v=nB98RvVLqMs

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Not All Genetic Diseases are Inherited: Germline and Somatic Variants

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https://www.youtube.com/watch?v=TNKWgcFPHqw

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https://www.youtube.com/watch?v=Qqe4thU-os8

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Year 11 Revision: Eukaryotic vs Prokaryotic cells

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Year 11 Revision: Eukaryotic vs Prokaryotic cells

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Create a Venn diagram that compares and contrasts the features of each cell.

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Interactive Resources from Biology Animations

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Interactive Resources from Biology Animations

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https://dnalc.cshl.edu/resources/animations/

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DNALC animations feature stunning visualizations of cellular and molecular processes. Journey inside a cell as you follow proteins in Cell Signals. Zoom along a three-dimensional rendering of 650,000 nucleotides of human chromosome in Chromosome 11 Flyover. Processes like DNA translation, transcription, replication, and more are explained in interactive animations.

# data[].attributes.attachment_link.description
DNALC animations feature stunning visualizations of cellular and molecular processes. Journey inside a cell as you follow proteins in Cell Signals. Zoom along a three-dimensional rendering of 650,000 nucleotides of human chromosome in Chromosome 11 Flyover. Processes like DNA translation, transcription, replication, and more are explained in interactive animations.

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https://www.yourgenome.org/activities/yummy-gummy-dna/

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This tasty activity helps you to explore the shape and structure of DNA. Four colours of gummy sweets represent the four bases that make up DNA. Using the toothpicks you can pair the bases correctly and make up the ladder-like shape of the DNA helix.

And the best part of the activity - it's edible!

DNA has the shape of a 'double helix'. It is comprised of two single strands that join and twist together. The strands contain four bases (adenine, cytosine, guanine and thymine), which bind together in complementary pairs (A with T, C with G). These bases act as the rungs of the ladder-like structure.

Age: All years

Which of these best describes your occupation?

how old are students / how old are you?

How has the site influenced you (or others)?

Thankyou, we value your feedback!

If you have any other comments or suggestions, please let us know at comment@yourgenome.org

Can you spare 5-8 minutes to tell us what you think of this website? Open survey

# data[].attributes.attachment_link.description
This tasty activity helps you to explore the shape and structure of DNA. Four colours of gummy sweets represent the four bases that make up DNA. Using the toothpicks you can pair the bases correctly and make up the ladder-like shape of the DNA helix. And the best part of the activity - it's edible!

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https://www.yourgenome.org/facts/timeline-organisms-that-have-had-their-genomes-sequenced/

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To develop techniques for DNA sequencing, scientists began by sequencing the genomes of small, simple organisms. As techniques improved it became possible to sequence the genomes of more complex organisms, such as the human genome. Now, we have a large catalogue of genomes that have been sequenced that we can study and compare.

1976

Bacteriophage MS2
Common name: Bacteriophage MS2

What is it? A single-stranded RNA virus that infects the family of bacteria that includes E. coli.

Why was it sequenced? This was the first genome to be completely sequenced.

Who sequenced it: Walter Fiers and his team" at the Laboratory of Molecular Biology at the University of Ghent, Belgium.

How many bases? 3,569 (one of the smallest genomes known)

How many chromosomes? 1

PhiX174
Common name: PhiX174

1995

Haemophilus influenza
Common name: Haemophilus influenza

Methanococcus jannaschii
​Common name: Methanococcus jannaschii

What is it? A heat-loving, methane-producing, single-celled organism.

Why was it sequenced? This was the first archaeon to be sequenced.

Who sequenced it? Craig Venter and his team" at The Institute for Genomic Research in Rockville, Maryland, USA.

How many bases? 1.7 million

How many chromosomes? 1 circular chromosome

1996

What is it? A species of yeast used in winemaking, baking and brewing.

Why was it sequenced? This was the first fungi to be sequenced.

Who sequenced it? The International Collaboration for the Yeast Genome Sequencing.

How many bases? 12.1 million

How many chromosomes? 32

1998

2000

2001

Why was it sequenced? Understanding the human genome will help us to improve human health.

Who sequenced it? The Human Genome Organisation (HUGO) and Celera Genomics.

How many bases? 3.2 billion

How many chromosomes? 23

2002

Why was it sequenced? Over 95 per cent of the mouse genome is similar to our own, so studying it is really useful for discovering more about human health and disease.

Who sequenced it? The Mouse Genome Sequencing Consortium (the Wellcome Trust Sanger Institute, The Whitehead Center for Genome Research, The Whitehead Center for Genome Research and The Genome Institute at Washington University in St Louis and The Broad Institute at MIT).

How many bases? 3.48 billion

How many chromosomes? 20

What is it? It is a flying insect which feeds" on the blood of animals.

Why was it sequenced? This species of mosquito is the principal vector of malaria, which kills over 1 million people each year.

Who s equenced it? Celera Genomics, USA and Genoscope, France.

How many bases? 278 million

How many chromosomes? 5

Common name: Rice

What is it? Rice is a staple food for millions of people across the globe.

Why was it sequenced? Rice is one of the most important crops so it is important to understand its genetics.

Who sequenced it? The Beijing Genomics Institute, Zhejiang University and the Chinese Academy of Sciences, China.

How many bases? 374 million

How many chromosomes? 12

2004

What is it? It is a recent ancestor of the domestic chicken.

Why was it sequenced? This is the first egg-laying animal to have its genome sequenced.

Who sequenced it? The International Chicken Genome Sequencing Consortium.

How many bases? 1 billion

How many chromosomes? 78

2005

What is it? Chimpanzee is one of the great apes along with gorilla, orangutan, bonobo and human.

Why was it sequenced? It was the first non-human primate genome to be sequenced.

Who sequenced it? The Chimpanzee Genome Project (Broad Institute at MIT and The Genome Institute at Washington University in St Louis).

How many bases? 3.3 billion

Number of chromosomes: 23

2010

What is it? Is a small frog native to Africa.

Why was it sequenced? Xenopus is a model organism commonly used to study early development.

Who sequenced it? The US Department of Energy's Joint Genome Institute and the University of California.

How many bases? 1.5 million

Number of chromosomes: 10

2013

Which of these best describes your occupation?

how old are students / how old are you?

How has the site influenced you (or others)?

Thankyou, we value your feedback!

If you have any other comments or suggestions, please let us know at comment@yourgenome.org

Can you spare 5-8 minutes to tell us what you think of this website? Open survey

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Timeline: Organisms that have had their genomes sequenced

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To develop techniques for DNA sequencing, scientists began by sequencing the genomes of small, simple organisms. As techniques improved it became possible to sequence the genomes of more complex organisms, such as the human genome. Now, we have a large catalogue of genomes that have been sequenced that we can study and compare.

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Wellbeing Activities: Biology Colouring In 

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Wellbeing Activities: Biology Colouring In 

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https://www.cell.com/comics

If you find Unit 4 a little overwhelming, take some time out and colour in eukaryotic cells, prokaryotic cells, the DNA double helix or the DNA replication fork (just to name a few).

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Good for Revision of Cell organelles & DNA

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Good for Revision of Cell organelles & DNA

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https://www.unlockinglifescode.org/resources-for-teaching-cells-organelles-and-dna

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Article on non-coding DNA (referred to as the Genome's Dark Matter)

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Article on non-coding DNA (referred to as the Genome's Dark Matter)

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https://www.bbc.com/future/article/20230412-the-mystery-of-the-human-genomes-dark-matter

If you are interested in learning more about 98% of the human genome (non-coding component) read this article published by BBC.

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When the 13-year-long effort to sequence the entire "book of life" encoded within the human genome was declared "complete" in April 2003, there were high expectations. It was hoped that the Human Genome Project, at a cost of around $3bn (£2.5bn), would yield treatments for chronic illnesses, and shed light on everything that is genetically determined about our lives.

But even as the press conferences were being held to herald the triumph of this new era of biological understanding, this instruction manual for human life had already thrown up an unexpected surprise.

At the time, the prevailing belief was that the vast majority of the human genome would consist of instructions for making proteins, the building blocks of all living organisms that perform a bewildering range of roles within and between our cells. With over 200 different types of cells in the human body, it seemed to make sense that each would need its own genes to carry out its necessary functions. The appearance of unique sets of proteins were thought to have been vital in the evolution of our species and our cognitive powers. (We are, after all, the only species capable of sequencing our own genome.)

Instead, it transpired that less than 2% of the three billion letters of the human genome are dedicated to proteins. Only around 20,000 distinct protein-coding genes were found to exist in the long lines of molecules known as base pairs that make up our DNA sequences. Geneticists were astonished to find that humans have similar numbers of protein-making genes to some of the simplest creatures on the planet. Suddenly the scientific world was faced with an uncomfortable truth: perhaps much of our understanding of what makes us human was actually wrong?

"I just remember the incredible shock," says Samir Ounzain, a molecular biologist and chief executive of a company called Haya Therapeutics, which is attempting to use our understanding of human genetics to develop new treatments for cardiovascular disease, cancer and other chronic illnesses. "That was the moment where people started wondering, 'maybe we have the wrong conceptualisation of biology?'"

The remaining 98% of our DNA became known as dark matter, or the dark genome, a mysterious melee of letters with no obvious meaning or purpose. Initially some geneticists suggested that the dark genome was simply junk DNA or the rubbish bin of human evolution - the remnants of broken genes which had long ceased to be relevant.

For others though, it was always obvious that the dark genome was crucial to our understanding of humanity. "Evolution has absolutely no tolerance for junk," says Kári Stefánsson, chief executive of the Icelandic company deCODE genetics, which has sequenced more whole genomes than any other institution in the world. "There must be an evolutionary reason to maintain the size of the genome."

Now, two decades on, we have the first inklings of the role of the dark genome. Its primary function appears to be regulating the decoding process, or expression, of protein-making genes. It helps to control how our genes behave in response to all the environmental pressures our bodies face throughout our lives, ranging from diet to stress, pollution, exercise, and how much we sleep, a field known as epigenetics.

Although the Human Genome Project was 'completed' 20 years ago, it was quickly clear that a great deal of the information contained in our DNA was missing (Credit: Alamy)

Ounzain says he likes to think of proteins as the hardware components of life, while the dark genome is the software, processing and responding to external information. As a result, the more we learn about the dark genome, the more we understand human complexity, and how we became who we are.

"If you think of us as a species, we're master adapters to the environment at every level," says Ounzain. "And that adaptation is the information processing. When you go back to the question of what makes us different to a fly or a worm, we've increasingly realised that the answers lie in the dark genome."
Transposons and our evolutionary past
As scientists first began sifting through the book of life in the mid 2000s, one of the biggest challenges was that the non-protein coding regions of the human genome appeared to be littered with sequences of repetitive DNA known as transposons. These repetitive sequences are so ubiquitous that they comprise nearly half the genome in all living mammals.

"Even assembling the first human genome was made more problematic by the presence of these repetitive sequences," says Jef Boeke, who runs the Dark Matter Project at New York University Langone, an academic medical centre in New York City. "Just analysing any kind of sequence is much easier if it's a unique sequence."

Initially, transposons were ignored by geneticists. Most genetic studies choose to focus purely on the exome - the small, protein-coding region of the genome. But over the past decade, the rise of more sophisticated DNA sequencing technologies have allowed geneticists to study the dark genome in greater detail than ever before. One experiment, where researchers deleted a specific transposon fragment in mice leading to half of the animal's pups dying before birth, illustrated that some transposon sequences may be critical to our survival.

Perhaps the best explanation for why transposons exist in our genomes could be that they are extremely ancient, dating back to the earliest life forms, says Boeke. Other scientists have suggested that they come from viruses which have invaded our DNA over the course of human history, before gradually being repurposed in the body to confer some useful purpose.

"Most of the time, transposons are pathogens which infect us, and they can infect cells in the germline, the type of cells that we pass on to the next generation," says Dirk Hockemeyer, assistant professor of cell biology at University of California, Berkeley. "Then they can get inherited, and lead to the stable integration into the genome."

Boeke describes the dark genome as acting like a living fossil record of crucial alterations in our DNA which occurred long ago in ancient history. One of the most fascinating elements of transposons is that they can move from one part of the genome to another - a behaviour which gives them their name - creating or reversing mutations in genes, sometimes with dramatic consequences.

The movement of a transposon into a different gene may have been responsible for the loss of the tail in the great ape family, which led to our species developing the ability to walk upright. "Here you have this one-time thing that happened which had a huge effect on evolution, giving rise to a whole lineage of great apes including us," says Boeke.

But just as our growing understanding of the dark genome is explaining more about evolution, it can also shed new light on why diseases emerge. Ounzain points out that if you look at genome-wide association studies (GWAS), which search for genetic variations among large numbers of people to identify those linked to disease, the vast majority linked to chronic illnesses like Alzheimer's, diabetes, and heart disease are not in the protein-coding regions, but in the dark genome.
The dark genome and disease
Panay in the Philippines is best known for shimmering white sands and a regular influx of tourists, but this idyllic setting hides a tragic secret. The island has the highest number of cases in the world of an incurable movement disorder called X-linked dystonia Parkinsonism (XDP). Like Parkinson's disease, people with XDP develop a range of symptoms affecting their ability to walk, as well as their capacity to respond quickly to various situations.

Since XDP was first discovered in the 1970s, it has only ever been found in people of Filipino descent, something which had long been a mystery until geneticists found that these individuals all have the same unique variant of a gene called TAF1. The onset of symptoms seems to be driven by a transposon in the middle of the gene, which is able to regulate its function in a way which causes harm to the body over time. It is thought that this gene variant first emerged around 2,000 years ago, before being passed on and becoming established in the population.

"The TAF1 gene is an essential gene, meaning it's required for the growth and multiplication of all cell types," says Boeke. "When you tweak its expression, you get this very specific defect that manifests as this horrible form of Parkinsonism."

This is a simple example of how some DNA sequences in the dark genome can control the function of various genes, either activating or repressing the process of turning genetic information into proteins in response to environmental cues.

How your genes shape who you are

The dark genome also provides instructions for the formation of various kinds of molecules, known as non-coding RNAs, which can have various roles ranging from helping to assemble proteins, blocking the process of protein production, or helping to regulate gene activity. "The RNAs produced by the dark genome act as the conductors in the orchestra, conducting how your DNA responds to the environment," says Ounzain.

It is these non-coding RNAs which are now increasingly being seen as the link between the dark genome and various chronic illnesses. The thinking goes that if we consistently give the dark genome the wrong signals, for example through a lifestyle of smoking, poor diet, and inactivity, the RNA molecules it produces can send the body into a disease state, altering gene activity in a way which increases inflammation in the body or promotes cell death. It is thought that certain non-coding RNAs can enhance the activity of or switch off a gene called p53, which normally acts to prevent the formation of tumours. In complex diseases like schizophrenia or depression, an entire cacophony of non-coding RNAs may be acting in synchrony to decrease or increase the expression of certain genes.
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But our growing appreciation of the dark genome's importance is already leading to new approaches for treating these illnesses. While the drug development industry has typically fixated on targeting proteins, some are realising that it may prove more effective to try and disrupt the non-coding RNAs which are controlling the genes in charge of these processes.

Beyond the Genome

It has been 20 years since the Human Genome Project was "completed", but this enormous effort to sequence and map the human "book of life" was only just the beginning. Far from closing the question of what makes our bodies tick and why they do so differently, research on the human genome has revealed a far more complex picture than anyone could have imagined. Beyond the Genome examines just how far our understanding of our genetics has come in the past two decades.
Other pieces in the series:

In the field of cancer vaccines, where companies conduct DNA sequencing on a patient's tumour sample to try and identify a suitable target for the immune system to attack, the majority of approaches have focused only on the protein-coding regions of the genome. However, German-based biotech CureVac is pioneering an approach where they analyse the non-protein coding regions as well in the hope of finding a target which can disrupt the cancer at its source.

Ounzain's company, Haya Therapeutics, are currently pursuing a drug development programme targeting a series of non-coding RNAs which drive scar tissue formation, or fibrosis, in the heart, a process which can lead to heart failure. One of the hopes is that this approach could minimise the side effects which come with many common medicines.

"The problem with drugging proteins is that there are only 20,000 or so in your body, and most of them are expressed in many different cells and pathways which are unrelated to the disease," says Ounzain. "But the dark genome is exquisitely specific in its activity. There are non-coding RNAs which regulate fibrosis only in the heart, so by drugging them, you have a potentially very safe medicine."
The unknowns
At the same time, some of the excitement has to be tempered by the fact that we have barely scratched the surface in terms of understanding how the dark genome functions. We know very little about what geneticists describe as the basic rules - how do these non-protein coding sequences communicate with each other to regulate gene activity? And how exactly do these complex webs of interactions manifest over long periods of time into disease traits, such as the neurodegeneration seen in Alzheimer's?

Vaccines and drugs that target the dark genome could offer new way of treating cancers and other diseases (Credit: Alamy)

"We're just at the beginning right now," says Hockemeyer. "The next 15 to 20 years will be all that - identifying specific behaviours in cells that could lead to disease, and then trying to identify the parts of the dark genome which could be involved in modifying these behaviours. But we now have tools to probe into this, which we didn't have before."

One such tool is gene editing. Boeke and his team are currently attempting to learn more about how the symptoms of XDP develop by replicating the TAF1 gene transposon insertion in mice. In future, a more ambitious version of this project could attempt to understand how non-protein coding DNA sequences regulate genes by building chunks of synthetic DNA from scratch and transplanting it into mouse cells.

"We are now involved in at least two projects where we take a huge chunk of DNA that does nothing, and then we try and install all these elements into it," says Boeke. "We place a gene there, put a non-coding sequence just in front of it, and another one far away, and see how this gene now behaves. We now have the tools to actually build bits of the dark genome from the bottom up and try to understand it."

Hockemeyer predicts that as we learn more, the genetic book of life will continue to throw up unexpected surprises, just as it did when the first genome was sequenced 20 years ago.

"There are a lot of questions," he says. "Is our genome still evolving over time? Will we be able to completely decode it? We are still in this dark, open space that we're venturing into, and there are a lot of really cool discoveries to be made."

--
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The mystery of the human genome's dark matter

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When the 13-year-long effort to sequence the entire "book of life" encoded within the human genome was declared "complete" in April 2003, there were high expectations. It was hoped that the Human Genome Project, at a cost of around $3bn (£2.5bn), would yield treatments for chronic illnesses, and shed light on everything that is genetically determined about our lives.

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YouTube clip on "Genome's Dark Matter" 5 mins

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YouTube clip on "Genome's Dark Matter" 5 mins

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https://www.youtube.com/watch?v=AJLxyp5PDeU&t

The clip explains how humans have mapped out the human genome but only know what 2% does.

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‘Dark DNA’ Is the Latest Mystery in the World of Genetics… But What Is It?

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https://www.sciencelearn.org.nz/resources/1651-nanometres-and-nanoscale#:~:text=As%20part%20of%20the%20International,a%20billionth%20of%20a%20metre.

This website has two interactive media that help students understand the scale of DNA in relation to other objects.

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A nanometre is a billionth of a metre. Nanoscale can refer to things less than 100 nanometres in size, or to materials so small that they behave differently to normal.

What is a nanometre?

Your fingernails grow about a nanometre every second. That means they grow 86,400 nanometres in a day, but that's still too small for you to notice a difference.

Look at it another way. If a nanometre was as long as your foot, a centimetre would be the distance from New Zealand to Australia.

A nanometre is very, very small - there are a million of them in a millimetre.

'Nano' means 'a billionth' (a billion is a thousand million), so:

a nanometre is a billionth of a metre

a nanosecond is a billionth of a second.

Compare a nanometre with some measurements you are more familiar with:

a metre

a centimetre (a hundredth of a metre)

a millimetre (a thousandth of a metre)

a micrometre (a millionth of a metre)

As part of the International System of Units (SI), the standard symbol for nanometre is nm.

You can measure metres, centimetres and millimetres with a ruler, but measuring anything smaller than that is harder. In fact, it is hard trying to even imagine something as small as a billionth of a metre. It helps if you compare things of different sizes.

The head of a pin

1,000,000 nm across

You can see these with your eyes unaided

A red blood cell

7000 nm across

You can see these using a light microscope

Transistor on latest computer chips

(there are up to 100 million of them)

You need an electron microscope or other device to see these

What is nanoscale?

There is no fixed definition for what nanoscale is, but there are a couple of things that are very important - small size and different properties.

Nanoparticle size

At least one dimension (height, length or depth) is less than 100 nm:

A nanotube can be much longer than 100 nm, but it is still called a nanoparticle because it is only about 3 nm wide.

A very thin film of material can be many centimetres wide, but if it is less than 100 nm thick, it is still called a nanofilm.

This definition of nanoscale tends to be used by people who create tiny devices such as pumps and motors out of a few atoms, or by people who deal with very thin surface coatings.

Nature of science

Many nanoparticles are ball-shaped, so all dimensions are small.

Nanoparticle properties

To many scientists, things are at the nanoscale if they are so small that they display different properties to the large scale material. This mostly happens when particles are only a few nanometres across.

For example, you may know that water boils at 100ºC (at a pressure of 1 atmosphere), but that is only true for large amounts of water. A drop of water only 5 nm across boils at 95.9ºC.

One nanoparticle can behave differently to another nanoparticle even if it is only slightly a different size. It may be a different colour, it may have a different melting point, or it may conduct electricity differently.

So, there is more than one definition of what is meant by nanoscale. Learning to understand and make use of these different properties of matter at the nanoscale is what nanoscience is about.

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A nanometre is a billionth of a metre. Nanoscale can refer to things less than 100 nanometres in size, or to materials so small that they behave differently to normal.

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https://learn.genetics.utah.edu/content/cells/scale/

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Some cells are visible to the unaided eye

The smallest objects that the unaided human eye can see are about 0.1 mm long. That means that under the right conditions, you might be able to see an amoeba proteus, a human egg, and a paramecium without using magnification. A magnifying glass can help you to see them more clearly, but they will still look tiny.

Smaller cells are easily visible under a light microscope. It's even possible to make out structures within the cell, such as the nucleus, mitochondria and chloroplasts. Light microscopes use a system of lenses to magnify an image. The power of a light microscope is limited by the wavelength of visible light, which is about 500 nm. The most powerful light microscopes can resolve bacteria but not viruses.

To see anything smaller than 500 nm, you will need an electron microscope. Electron microscopes shoot a high-voltage beam of electrons onto or through an object, which deflects and absorbs some of the electrons. Resolution is still limited by the wavelength of the electron beam, but this wavelength is much smaller than that of visible light. The most powerful electron microscopes can resolve molecules and even individual atoms.

Adenine

The label on the nucleotide is not quite accurate. Adenine refers to a portion of the molecule, the nitrogenous base. It would be more accurate to label the nucleotide deoxyadenosine monophosphate, as it includes the sugar deoxyribose and a phosphate group in addition to the nitrogenous base. However, the more familiar "adenine" label makes it easier for people to recognize it as one of the building blocks of DNA.

How can an X chromosome be nearly as big as the head of the sperm cell?

No, this isn't a mistake. First, there's less DNA in a sperm cell than there is in a non-reproductive cell such as a skin cell. Second, the DNA in a sperm cell is super-condensed and compacted into a highly dense form. Third, the head of a sperm cell is almost all nucleus. Most of the cytoplasm has been squeezed out in order to make the sperm an efficient torpedo-like swimming machine.

The X chromosome is shown here in a condensed state, as it would appear in a cell that's going through mitosis. It has also been duplicated, so there are actually two identical copies stuck together at their middles. A human sperm cell contains just one copy each of 23 chromosomes.

A chromosome is made up of genetic material (one long piece of DNA) wrapped around structural support proteins (histones). Histones organize the DNA and keep it from getting tangled, much like thread wrapped around a spool. But they also add a lot of bulk. In a sperm cell, a specialized set of tiny support proteins (protamines) pack the DNA down to about one-sixth the volume of a mitotic chromosome.

Carbon

The size of the carbon atom is based on its van der Waals radius.

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The smallest objects that the unaided human eye can see are about 0.1 mm long. That means that under the right conditions, you might be able to see an amoeba proteus, a human egg, and a paramecium without using magnification. A magnifying glass can help you to see them more clearly, but they will still look tiny.

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https://htwins.net/scale2/

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https://www.youtube.com/watch?v=M4ut72kfUJM

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https://www.biointeractive.org/classroom-resources/activity-double-helix

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Activity for The Double Helix | This activity explores the concepts and research presented in the short film The Double Helix, which tells the story of the discovery of the molecular structure of DNA.

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Science History Institute: DNA Discovery

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Science History Institute: DNA Discovery

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https://sciencehistory.org/education/scientific-biographies/james-watson-francis-crick-maurice-wilkins-and-rosalind-franklin/

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At King's College London, Rosalind Franklin obtained images of DNA using X-ray crystallography, an idea first broached by Maurice Wilkins. Franklin's images allowed James Watson and Francis Crick to create their famous two-strand, or double-helix, model.

In 1962 Watson (b. 1928), Crick (1916-2004), and Wilkins (1916-2004) jointly received the Nobel Prize in Physiology or Medicine for their 1953 determination of the structure of deoxyribonucleic acid (DNA). Wilkins's colleague Franklin (1920-1958), who died from cancer at the age of 37, was not so honored. The reasons for her exclusion have been debated and are still unclear. There is a Nobel Prize stipulation that states "in no case may a prize amount be divided between more than three persons." The fact she died before the prize was awarded may also have been a factor, although the stipulation against posthumous awards was not instated until 1974.

Discovering the Structure of DNA

The molecule that is the basis for heredity, DNA, contains the patterns for constructing proteins in the body, including the various enzymes. A new understanding of heredity and hereditary disease was possible once it was determined that DNA consists of two chains twisted around each other, or double helixes, of alternating phosphate and sugar groups, and that the two chains are held together by hydrogen bonds between pairs of organic bases-adenine (A) with thymine (T), and guanine (G) with cytosine (C). Modern biotechnology also has its basis in the structural knowledge of DNA-in this case the scientist's ability to modify the DNA of host cells that will then produce a desired product, for example, insulin.

The background for the work of the four scientists was formed by several scientific breakthroughs: the progress made by X-ray crystallographers in studying organic macromolecules; the growing evidence supplied by geneticists that it was DNA, not protein, in chromosomes that was responsible for heredity; Erwin Chargaff's experimental finding that there are equal numbers of A and T bases and of G and C bases in DNA; and Linus Pauling 's discovery that the molecules of some proteins have helical shapes-arrived at through the use of atomic models and a keen knowledge of the possible disposition of various atoms.

Wikimedia Commons/From the personal collection of Jenifer Glynn

Rosalind Franklin

Of the four DNA researchers, only Rosalind Franklin had any degrees in chemistry. She was born into a prominent London banking family, where all the children-girls and boys-were encouraged to develop their individual aptitudes. She attended Newnham College, one of the women's colleges at Cambridge University. She completed her degree in 1941 in the middle of World War II and undertook graduate work at Cambridge with Ronald Norrish, a future Nobel laureate.

She resigned her research scholarship in just one year to contribute to the war effort at the British Coal Utilization Research Association. There she performed fundamental investigations on the properties of coal and graphite. She returned briefly to Cambridge, where she presented a dissertation based on this work and was granted a PhD in physical chemistry.

After the war, through a French friend, she gained an appointment at the Laboratoire Centrale des Services Chimiques de l'Etat in Paris, where she was introduced to the technique of X-ray crystallography and rapidly became a respected authority in this field. In 1951 she returned to England to King's College London, where her charge was to upgrade the X-ray crystallographic laboratory there for work with DNA.

Maurice Wilkins

King's College London and Horace Freeland Judson

Already at work at King's College was Maurice Wilkins, a New Zealand-born but Cambridge-educated physicist. As a new PhD he worked during World War II on the improvement of cathode-ray tube screens for use in radar and then was shipped out to the United States to work on the Manhattan Project.

Like many other nuclear physicists, he became disillusioned with his subject when it was applied to the creation of the atomic bomb; he turned instead to biophysics, working with his Cambridge mentor, John T. Randall-who had undergone a similar conversion-first at the University of St. Andrews in Scotland and then at King's College London.

It was Wilkins's idea to study DNA by X-ray crystallographic techniques, which he had already begun to implement when Franklin was appointed by Randall. The relationship between Wilkins and Franklin was unfortunately a poor one and probably slowed their progress.

James Watson and Francis Crick

Meanwhile, in 1951, 23-year-old James Watson, a Chicago-born American, arrived at the Cavendish Laboratory in Cambridge. Watson had two degrees in zoology: a bachelor's degree from the University of Chicago and a doctorate from Indiana University, where he became interested in genetics. He had worked under Salvador E. Luria at Indiana on bacteriophages, the viruses that invade bacteria in order to reproduce-a topic for which Luria received a Nobel Prize in Physiology or Medicine in 1969.

Watson went to Denmark for postdoctoral work, to continue studying viruses and to remedy his relative ignorance of chemistry. At a conference in the spring of 1951 at the Zoological Station at Naples, Watson heard Wilkins talk on the molecular structure of DNA and saw his recent X-ray crystallographic photographs of DNA. He was hooked.

Watson soon moved to the Cavendish Laboratory, where several important X-ray crystallographic projects were in progress. Under the leadership of William Lawrence Bragg, Max Perutz was investigating hemoglobin and John Kendrew was studying myoglobin, a protein in muscle tissue that stores oxygen. (Perutz and Kendrew received the Nobel Prize in Chemistry for their work in the same year that the prize was awarded to the DNA researchers-1962.)

A. Barrington Brown

Working under Perutz was Francis Crick, who had earned a bachelor's degree in physics from University College London and had helped develop radar and magnetic mines during World War II. Crick, another physicist in biology, was supposed to be writing a dissertation on the X-ray crystallography of hemoglobin when Watson arrived, eager to recruit a colleague for work on DNA.

Inspired by Pauling's success in working with molecular models, Watson and Crick rapidly put together several models of DNA and attempted to incorporate all the evidence they could gather. Franklin's excellent X-ray photographs, to which they had gained access without her permission, were critical to the correct solution. The four scientists announced the structure of DNA in articles that appeared together in the same issue of Nature.

Separate Career Paths

Then they moved off in different directions. Franklin went to Birkbeck College, London, to work in J. D. Bernal's laboratory, a much more congenial setting for her than King's College. Before her untimely death from cancer she made important contributions to the X-ray crystallographic analysis of the structure of the tobacco mosaic virus, a landmark in the field. By the end of her life she had become friends with Francis Crick and his wife and had moved her laboratory to Cambridge, where she undertook dangerous work on the poliovirus. Wilkins applied X-ray techniques to the structural determination of nerve cell membranes and of ribonucleic acid (RNA)-a molecule that is associated with chemical synthesis in the living cell-while rising in rank and responsibility at King's College.

Watson's subsequent career eventually took him to the Cold Spring Harbor Laboratory (CSHL) of Quantitative Biology on Long Island, New York, where as director from 1968 onward he led it to new heights as a center of research in molecular biology. From 1988 to 1992 he headed the National Center for Human Genome Research at the National Institutes of Health. Afterward he returned to CSHL as chancellor. Watson's racist remarks about the intelligence of Africans in 2007 led the CSHL to force him into retirement, though the Lab named him an emeritus professor and honorary trustee.

When Watson doubled down on his racist views in a 2018 documentary, the lab revoked these honors and severed ties with Watson. Watson's fame as a discoverer of the structure of DNA also made his continued public expression of sexist views on women in science and his previous eugenicist comments on homosexuality particularly harmful during the first decades of the 21st century.
The information contained in this biography was last updated on July 28, 2022. Featured image: Rosalind Franklin in Paris, ca. 1949. Vittorio Luzzati.

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Francis Crick, Rosalind Franklin, James Watson, and Maurice Wilkins | Science History Institute

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These four scientists-Crick, Franklin, Watson, and Wilkins-codiscovered the double-helix structure of DNA, which formed the basis for modern biotechnology.