Genes, DNA, and RNA -
Last time we left off with Mendel’s experiments on inherited traits (or phenotypes) of peas. We mentioned these traits are passed down from their DNA sequence and genes.
But what do we mean by DNA sequence?
The structure of DNA was elucidated in the early 1950’s by Francis Crick and James Watson using data that were generated by Rosalind Franklin. Franklin used a difficult technique to work on the structure called X-Ray crystallography.
If a protein or other material can be induced to form a crystal (think of making rock candy!) the structure of the material will affect the way photons (in this case X-Rays like your dentist uses) pass through the crystal. The photons are re-directed by interactions with atoms in the crystal, they are refracted. The pattern of refraction is identified by using film that the X-Rays can expose.
As you might imagine the patterns of refraction can be very complex and interpreting them is no simple task. In the 1940s when the work began the act of obtaining crystals and exposing them to X-Rays was a major undertaking that only a few labs were capable of. At the end the refraction pattern needed to be translated into a structure (what atoms are connected to what and what is the shape of the molecule) and that undertaking was a huge intellectual puzzle that occupied some of the best minds of the time.
In the end the iconic double helical structure emerged, but most importantly the structure revealed that there were four basic building blocks to the DNA molecule, called nucleotides and that these building blocks were built into each helical strand of the double helix. Most importantly and impossibly amazing was that nucleotide building blocks on each strand of the double helix could interact chemically in a very specific way. That is a strong attraction called a covalent bond formed between pairs of nucleotides, such that the A on one strand bound to the T on the other strand and C bound to G.
So a DNA sequence is the linear array of ATCG along the helix. This arrangement immediately suggested both a way that information could be imparted by DNA and a way by which that information could be inherited.
KEY MOMENTS IN DNA HISTORY
- 19th century-inherited characteristics defined by discrete entities
- Early 20th century concept of “gene” well established but no idea what it was
- Debate the chemical nature of a “gene” protein vs. DNA
- Avery, McCarty, MacLeod show DNA responsible for the transmission of heritable traits
- Structure of DNA solved
- Base pairing code cracked
- Central dogma well established DNA → RNA → protein
- Endonucleases discovered
- Reverse transcriptase discovered — Central Dogma revisited
- Genome project
WHAT IS A GENE?
Hereditary entity to produce a protein or a functional RNA comprising:
- Linear DNA sequence that directs transcription
- Promoter to control transcription
- Enhancer sequences to regulate transcription
- Associated proteins
WHAT IS DNA
- A linear strand of deoxyribose sugar and a base (cytosine, thymine, adenine or guanine; C, T, A, or G) polymerized (concatenated) into two long strands that bind to each other and form a double helical structure (Figure 2)
FIGURE 2 — DNA double helix on left, the sugar backbone is shown as a ribbon, the representation of the base looks like a lollipop. On the right a 4-base pair segment is enlarged to show the base pair chemical bonds. Guanine (G) binds cytosine ©, thymine (T) binds adenine (A). This binding allows faithful transmission of information to replicated DNA (at cell division and in the next generation) and to RNA to direct synthesis of protein by specifying the amino acids that make up the protein. Information is embedded in the linear sequence of bases (A,T,C, and G) as a triplet code in which three letters define an amino acid. A nucleotide (nt) is one sugar molecule (deoxyribose) bound to one base.
The figure is from: Understanding DNA and Gene Cloning, Drlica, 1984
WHAT IS RNA
- Like DNA but ribose not deoxyribose and uracil not thymine (Figure 3)
- Pre-mRNA → mRNA by splicing introns out (Figure 4)
- mRNA moves out of nucleus connects to ribosomes in cytoplasm to make protein by connecting a chain of amino acids
- Some RNAs stay in nucleus and regulate other genes
- Mostly single stranded with many conformational shapes
- Some regulatory RNAs are non-protein coding
FIGURE 3 — This is a structural depiction of the hairpin loop in a messenger RNA (mRNA) molecule. The sugar backbone (in RNA it is made of ribose) is represented by the ribbon. RNA is usually single stranded, it utilizes uracil rather than thymine as a base.
FIGURE 4 — Diagram of a gene. The thin line represents a DNA strand stretched out. A gene has a promoter that directs transcription of the DNA to RNA, exon sequences (that remain in the RNA when it leaves the nucleus), intron sequences (that are spliced out of the RNA before it leaves the nucleus), and enhancer sequences (that bind regulatory proteins).
In order to activate a gene the DNA must first be unwound from nucleosomes. The strands of the double helix are opened up and an RNA polymerase is bound to the gene. This is controlled by transcription factors forming protein complexes on the promoter and enhancers of the gene. This synthesizes the RNA, which is processed into mRNA and moved out of the nucleus to be translated into proteins by ribosomes that direct the attachment of amino acids into the growing protein following the instructions provided by the RNA sequence.
WHAT IS EPIGENETICS
- Chemical modification of bases (cytosine → methyl cytosine) in DNA
- Chemical modification of histones in nucleosomes (alter access of regulation and polymerase to gene)
- These modifications regulate gene expression
- The modifications can be mis-set or altered changing the developmental gene expression pattern
- The modifications are heritable and mistakes will transmit to the next generation
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Originally published at lcresearchcenter.tumblr.com.