Genetics 101

[Copasetic]

I’ve decided to make a topic, as per the request of a couple of members, about gene expression and molecular biology. This is only going to be the basics, a sort of quick and dirty guide to DNA/RNA and genes. I’ll be skipping over more complex mechanisms such as frame shift reading, slippery reading and many other viral or eukaryotic splicing mechanisms. So if you have had lots of biology classes and you are reading along and say wait “Copasetic there is 30 more things that make prokaryotes distinct from eukaryotes” –I know. I am trying, as I said, to keep it simple so that everyone can benefit. If you have had that much biology, you’ll likely not benefit and should return to your 500 level classes!

I am going to divide this up into 3 parts. If you use Firefox simply type (in the page search box) a period followed by the section name to jump to a specific part.

Part one will be about DNA/RNA (.DNA)

Part two will be about Proteins (.Proteins)

Part three will be about genetics and the expression of genes (.Genetics) If anyone would like to a write up on Mendelian genetics please feel free I will divide this into two parts:

Part 3A will be the “central dogma of molecular biology” (.3A)

Part 3B will be a brief on Genotype to Phenotype and what this means for biology. (.3B)

First I would like to provide a little bit of background on cells and organisms so that some of this may make sense.

Cell theory is one of the foundations of modern biology, it seeks to explain cells and their nature, in a similar way atomic theory explains atoms.

It has 5 major tenets (well typically 3, but I prefer to expand these);

1. All living things (what we define as living) are made up of cells.

2. The cell is the structural and functional unit of living organisms.

3. All cells originate from preexisting cells through the reproductive processes (divisions).

4. Cells contain hereditary information which is passed on during those divisions.

5. All energy generating processes necessary for life are done within cells.

We have two types of cells: The simple kind (prokaryotes) and the more complex kind (eukaryotes). Prokaryotes, while simple are extremely versatile and are found in almost every environment on earth; from your own body to boiling natural baths of sulfuric acid. Even though we consider prokaryotes “simple” this is not to say they are less evolved than eukaryotes. They have been on earth for over 3.5 billion years and every bit as evolved (arguably more) than eukaryotes. Eukaryotes are the multicellular organisms, such as plants and animals. There are also some single celled eukaryotes, we call the protozoans. Prokaryotes and eukaryotes differ in some important ways, which we’ll talk about later with genetics and DNA. For now I am going to simply list the differences.

Prokaryotes: Lack membrane bound organelles, including a nucleus. They have a cell wall, cell membrane, ribosomes which are free floating and nucleoid. The nucleoid is region for the localization of prokaryotes genetic material.

Eukaryotes: Have membrane bound organelles, such as mitochondria (our cellular powerhouse), endoplasmic reticulum, lysosomes and vacuoles. They also store their genetic material in nice, neat, little organized things called chromosomes.

I’ve included some lovely little pictures, courtesy of Google Image 

Eukaryote:

Prokaryote:

Part I, DNA and RNA(.DNA)

DNA is the “carrier” of our hereditary information. It transmits traits across generations.

To start with, what is DNA? It stands for deoxyribonucleic acid. Nucleic acids follow a basic type of chemistry. They are made of a sugar, a base and a phosphate group. The base can be many different things, in DNA it is 1 of 4 molecules: Adenine (A), Guanine (G), Thymine (T) or Cytosine ©. The general layout looks something like this:

These single nucleotides come together to make the polymers we call DNA.

RNA, another nucleic acid, is similar to DNA. Instead of deoxyribo it is ribonucleic acid and as you probably figured out, has some additional oxygen An important difference with RNA is the base thymine is replaced by the base uracil (U).

**Don’t let our letter soup fool you, remember when we are abbreviating nucleotide bases that abbreviation is a 3 dimensional molecule**

DNA is a double helix, which means there are two complimentary strands. The strands are held together through hydrogen bonding between matching bases; Adenine pairs with thymine (A-T) and cytosine pairs with guanine (C-G). In RNA, uracil simply replaces the thymine in the pairing with adenine.

**Quick break for chemistry review: A hydrogen bond is a weak bond that occurs between a hydrogen atom with a slight positive charge and nitrogen, oxygen or fluorine atom with a slight negative charge**

[Copasetic]

Part II, Proteins (.Proteins)

Proteins are another type of molecule used by living things. They are extremely diverse. Some are attached to the ends carbohydrates or fats, some work as digestive enzymes, some provide stability and structure to cells and others maybe use to modify DNA.

Proteins are a heterozygous polymer composed of subunits called amino acids. Amino acids (AA) all have the basic structure:

The “R” group can be many different things and determines the properties of the AA. Linked together they form proteins. We use abbreviations for amino acids as well.

**Disregard the other information on the chart and just use the first 3 columns form the left (Name, 3 and 1 letter symbols)**

It is important to understand the different levels of protein structure.

The primary structure is the protein’s AA sequence.

This is going to be pretty boring and will be something like:

Ala-Asn-Pro-Pro-Thr-Tyr-Trp-Pro-His-His-His-Arg

Or

A-R-D-C-C-C-E-Q-G-H-H-M-F-P-P

The secondary structure is regular stability bonding that occurs through hydrogen bonding (remember our quick break for chemistry above).

The most common secondary structures are alpha helices and beta pleated sheets. Beta sheets make a (surprise, surprise) sheet, while helices make helices with their hydrogen bonds

Beta sheet:

Alpha helix:

The tertiary structure is the combined shapes of the secondary structure of a single protein molecule. There is also other repulsions/attractions caused by the eletronature of the other AAs, salt bridging, disulfide bonding and any modifications the cell may do to the protein (such as sticking on a carbohydrate chain).

The final structure is the quaternary structure, which is the shape of multiple protein molecules complexed together. Each molecule we call a subunit.

In this neat looking guy here, each color represents a different subunit. There are 2 reds and 2 blues for a total of 2 subunits. The greens are some of those modifications we were talking about and are iron-containing organic molecules we call hemes. This, at a molecular level, is what hemoglobin looks like.

Part III, Genetics (.Genetics)

On to the fun part!

First I want to just define a couple of things, I know definitions are not much fun, but it will make it easier and less vague to use real terminology.

Gene: Discrete unit of inheritance, we used to consider responsible for a “trait”. We know now this isn’t necessarily the case.

Allele: Alternate forms of a gene. There usually exists within a population, a few to a lot of different “flavors” of genes.

Genotype: All the alleles an organism has.

Phenotype: The expression of those alleles

Trait: The distinct, expressed phenotypic character of an individual that can be inherited or environmentally determined.

Edited March 28, 2009 by Copasetic

[Copasetic]

The Central Dogma of Molecular Biology (.3A)

I know this is big and unsightly, but this is the gist of it.

So you notice in our nice big image there, our first step is transcription. Transcription is the process of “reading” the DNA. We have enzymes called polymerases. In this instance we, and other cells, have an enzyme called RNA polyermerase: Which surprisingly, polyermerizes RNA (no one said biologists were creative ). The RNA polymerase binds to a promoter region of the DNA. A promoter region is an area the polymerase recognizes as the start of a gene. As the polymerase moves down the DNA strand, it pairs complimentary bases of RNA to the DNA. This synthesizes a strand of RNA, specifically messenger RNA or mRNA; Named so, because it “transmits” a message.

Here is one of those important differences between prokaryotes and eukaryotes. In prokaryotes the RNA is ready to go, in eukaryotes the DNA is a little more complicated and a piece of RNA is made we call a primary transcript. The primary transcript is altered and spliced and finally made into messenger RNA. In prokaryotes this process (transcription) takes place inside the cytoplasm of the cell, while in eukaryotes it takes place in the nucleus.

And a picture to go with all that reading!

Eukaryotes:

Prokaryotes:

Now that we have a piece of mRNA we can start making proteins. The mRNA is sent to another important structure, called the ribosome. The ribosome works by reading the nucleotide bases of the RNA. It reads them in 3’s, and we call 3 bases a codon. A codon “codes” for an amino acid.

So we can see from the nice big chart, which 3 bases code for which amino acids. For example, if there was an adenine, adenine and guanine (AAG) then we get a Lysine.

***Remember in RNA, uracil replaces thymine***

Translation starts when the ribosome ‘reads’ a start codon- AUG. Translation is terminated (no more AA polymerization) when the ribosome reads a stop codon.

Here we have a picture of translation. The big purple, goobley-guy is our ribosome and the black wispy lines are another type of RNA; transfer RNA (tRNA). tRNA plays an important role in this process, it brings new amino acids to the ribosome, so that the elongation of the AA chain can continue.

So this process creates our primary protein structure (Remember AA sequence). After the AA sequence is released, hydrogen bonding can occur and we develop our secondary structure. Some proteins are finished at this point, others get some of those special modifications we talked about: Such as, getting some carbohydrates or lipids added to them. Others still, require special helper proteins to finish their folding, which we call chaperone proteins. Chaperones help with the tertiary and quaternary folding.

That’s how we make proteins in a nutshell!

Part 3b, Genotype to Phenotype (.3b)

One of the questions other members asked me was; how does this process above, lead to a phenotype?

Our protein expression is our phenotype. It can be hard to think of a trait as protein, but that is the fact of the matter. How we express our genes and when is what leads to our phenotype and this expression is accomplished through the “central dogma of molecular biology”.

There are some catches though. Not surprisingly, genetics isn’t quite this simple or straightforward. It turns out, that our environment controls a large portion of our phenotype- Not just our genes. Let me give one of my favorite examples of gene-environment interactions.

Siamese cats have some neat coloration, which of course –Has something to do with their genes.

The genes that control pigment in the cat are temperature dependent. The cooler parts of the body have more pigment and turn out darker, while the warmer parts of the body have less pigment and are lighter.

To anyone that has ever owned a Siamese cat; they probably noticed the cats coat gets darker in the winter, especially around the legs and tail.

So what does all this have to do with biology and evolution? Which I think some of people asking question may have been wondering about. Evolution, more specifically natural selection, acts on our phenotypes and by acting on our phenotype, it indirectly chooses genotypes.

These are probably the examples many of you are more familiar with, where evolution “chooses” the larger ears or bigger beak. It is important to remember though, that traits with an underlying genetic basis (meaning they are hereditary) are what is transmitted through generations. These traits, have a specific genotype, which gets expressed by the rough explanation above.

Hope that helped clear up any problems anyone was having. Apologies this took me so long to get up, I know I had said it would be in a couple hours, which turned out to be days. Any questions, comments, arguments etc, feel free to add them

Edited March 28, 2009 by Copasetic

[Cimber]

Lots of valid and sound information here for those interested in knowing more about biology in general.