8 - It's in Their Genes (Nucleic Acids I) (w/ Donna Haines & Dale Ayton!)
8. It's in Their Genes (Nucleic Acids I)
Why can’t I give birth to an elephant? Why do each of my feet have five toes and not three toes and two conjoined toes? What is DNA and how is it so fundamentally important to how each of us develop? Today, we’ll discuss DNA, the central dogma, and twins. Let’s learn to be scientifically conversational.
General Learning Concepts
1) Just what the heck is DNA?
a. Deoxyribonucleic acid: It’s its own novel biomolecule; not protein, lipid, or carbohydrate. It encodes for an organism’s genetic blueprint: all of the information required to build and maintain an organism. DNA is contained within a cell, be it animal, plant, bacterial, archaeal, or even in some viruses.
b. DNA Components: Just as you can reduce the overall dish of a seven-layer dip to each of the individual ingredients, you can also reduce DNA into chemical building blocks: nucleotides. There are three important overall parts: 1) a phosphate group (chemical compound made of phosphorous and oxygen atoms), 2) a sugar group (2-deoxyribose, a ribose ring that is missing a 2’ hydroxyl group), and 3) a nitrogen-rich base like adenine (A), cytosine (C), guanine (G), and thymine (T). It’s an acid because the molecule has lost a hydrogen and now carries a negative charge and makes the molecule soluble.
c. DNA structure and macromolecular complexes: DNA nucleobases recognize each other by a weak force called hydrogen bonding (think very weak, specific magnets): specifically, G bonds with C and A bonds with T. This leads to the famous “double helix” structure that is such a hallmark of DNA (think a twisted ladder). Each rung of the ladder is a nitrogenous base (the other side of the rung is the corresponding base) and the outside of the ladder is the alternating phosphate group and sugar.
i. There are three billion bases of DNA in a human genome (instruction book), and about 20,000 genes (a gene is the DNA sequence important to make a particular molecular machine, eg. a protein). Most DNA is found in a special compartment of the cell called the nucleus, but some can be found in mitochondria (the powerhouse of the cell). Naturally, all of this DNA cannot be a long, linear strand in a cell (interesting because DNA is intrinsically a linear molecule) so instead it’s spooled around proteins called histones that allow for larger structures called chromosomes to be formed (two sets of 23 chromosomes). These chromosomes range in size depending on what the cell is doing but can be as small as 1 uM, or approximately the size of particles we try to filter out of our water, some bacteria, or 10 times larger than the influenza virus we discussed in episode 3.
d. How does DNA contain information? What is heredity? Heredity refers to the genetic transmission of traits from parents to offspring. Heredity helps explain why children tend to resemble their parents, as well as how a genetic disease runs in a family. The sequence of nucleotides gives a distinct line of information. You can almost relate this to computer programming in binary, with T (00), A (10), C (01), G (11). Just as it’s incredible to believe that entire computer programs come from strings of 0’s and 1’s, biological complexity is derived from strings of A, T, G, and C’s. “Taken as a whole, this package of DNA serves as its owner’s complete genetic blueprint. Just as no two humans are alike, no two blueprints — except those belonging to identical twins — are, either.”
2) The Central Dogma:
a. What is the central dogma? The definition from the textbook Molecular Cell Biology states “the coded genetic information hard-wired into DNA is transcribed into individual transportable cassettes, composed of messenger RNA (mRNA); each mRNA cassette contains the program for synthesis of a particular protein (or small number of proteins)." In simpler terms: in a cell, DNA is used to make DNA and RNA, RNA is used to make protein. DNA to DNA is replication. DNA to RNA is transcription. RNA to protein is translation.
b. How is RNA different than DNA? Is DNA the only nucleic acid? RNA is ribonucleic acid: it differs from DNA chemically in that it has ribonucleotides (ribose instead of deoxyribose) and that it contains uracil (U) instead of thymine (T). Uracil can still base pair with adenine, so all is well for RNA. RNA does not occupy the famous structure of DNA, the double helix, but is capable of folding into many different interesting shapes (hairpins, cloverleaves, or just a single strand).
c. Examples of the Central Dogma in non-biological contexts: DNA carries information; that DNA can be transcribed to form RNA, often thought as mRNA (messenger RNA). That RNA can be translated into protein. Think of it as:
i. DNA is a cookbook. A chef reads that cookbook and yells instructions to another cook. Yelling the message is the RNA. That message results in a product; a cooked meal or a protein.
ii. DNA is a high-level executive who only speaks to a middle manager. RNA is the middle manager who speaks to the workforce. The protein is the eventual product that is made from the workforce. This example might be useful because a middle manager might also have a slightly different message than the high-level executive from before: this could be from a variety of different biologically relevant factors.
iii. DNA is a script. A telemarketer reads that script to try to sell you a product. The spiel is the RNA. That message results in a reaction of you potentially buying a product; a successful purchase or a protein.
iv. These are all useful examples because even though most cells contain the same copies of DNA, they can’t all use DNA in the same way. You wouldn’t want your liver cells beating like a heart; they might have the DNA instructions to do so, but the DNA might be inaccessible to make RNA, the RNA might be degraded quickly (weak voice for reading instructions), or so on.
3) Examples of current DNA research
a. Sequencing genomes: Understanding the genetic impacts of having specific DNA sequences that vary from other human beings may give understanding on a wealth of different genetic factors from balding to disease. Knowing human genetic variation can help humans understand specific mutations that are beneficial to human health, like why those with heterozygous sickle cell hemoglobin have a selective advantage in areas with endemic malaria or why individuals with mutations in CCR5 proteins are resistant to HIV.
b. Epigenetics: DNA modifications that do not alter how the sequence affects gene activity. Essentially, you can think about it as a dimmer switch for a light – genes that can be turned off, turned on, or regulated to some certain level. Another example is from Nessa Carey’s “The Epigenetics Revolution”:
i. Think of the human lifespan as a very long movie. The cells would be the actors and actresses, essential units that make up the movie. DNA, in turn, would be the script — instructions for all the participants of the movie to perform their roles. Subsequently, the DNA sequence would be the words on the script, and certain blocks of these words that instruct key actions or events to take place would be the genes. The concept of genetics would be like screenwriting. Follow the analogy so far? Great. The concept of epigenetics, then, would be like directing. The script can be the same, but the director can choose to eliminate or tweak certain scenes or dialogue, altering the movie for better or worse. After all, Steven Spielberg’s finished product would be drastically different than Woody Allen’s for the same movie script, wouldn’t it?
4) Fun Tidbits
a. Twins have very similar genetic make-up: Twins derive from the same single fertilized egg, which contains one single genome, from the mother and father. However, twins can have DNA differences from differential DNA replication (a monk copies the books in the genetic library but has to work so fast there are occasionally mistakes – Grey Monroe, Ph.D candidate at The Colorado State University). There can be differences in the number of copies of certain pieces of DNA. Twins have different fingerprints due to physical developmental differences in-utero.
b. Not all pieces of DNA are immediately thought to be “as useful”: Transcription of DNA into RNA results in an RNA that might have extra information. An exon is the RNA sequence in the transcript that is found in the messenger RNA, while the RNA sequences that are removed are known as introns. Having introns is a eukaryotic trait; it isn’t completely understood as to why.
5) Solicited Naïve Questions
a. Are all traits hereditable? Join us for more on this topic next week!
b. Do all living things use DNA as their method of heredity? All organisms that are capable of self-reproducing have DNA as the genome. However, many viruses have RNA genomes of varying polarity while some viruses have a DNA genome.