BOLO Biology Newsletter Archive: March 2012

Friday, March 30, 2012

Daily Newsletter March 30, 2012

Evolution Friday!

Please read the following article on mammalian gene expression. It is a short, and fairly simple, open source article.

Read the following two articles Neutral Theory.

Daily Challenge:

Evolution has its base in genetics. All variation starts with mutation. The addition, deletion or change in the nucleotide sequence of a coding region can result in protein changes. Any mutation, if it has an expressed effect, then becomes subject to the mechanism of Natural Selection.

A great example of this nucleotide alteration is seen in Sickle Cell Anemia. A change in one nucleotide causes a conformational change in the beta-hemoglobin chain, which causes the entire expression of the disease.

Your task today is to discuss the relationship DNA changes and Gene Expression has with evolution. Sit with the concept for a moment, and come up with a coherent discussion. Feel free to use models such as Sickle Cell Anemia. Remember, this alteration in gene expression sets up the diversity of the population. Natural Selection then acts on the new phenotype.

Thursday, March 29, 2012

Daily Newsletter March 29, 2012

Today's Topic: Translation

The core concept of translation is the connecting of a codon to an amino acid. As we saw yesterday, this is accomplished with the Transfer RNAs. What that leaves us with then is the actual mechanism of amino acid polymerization.

Initiation of Transcription
Protein function is determined by the sequence of amino acids. This sequence allows the protein to fold into the correct configuration to produce activity. Any variation in the sequence could produce alterations to function, or even result in non-functionality. In order to generate the correct sequence, we must first establish the correct reading frame of codons. We must first find the start codon on mRNA.

The small subunit of the Ribosome (40s in eukaryotes) is built to find the Start Codon (AUG) and will align the full ribosome with the correct reading frame. A number of proteins will help the alignment, and in the formation of the full (holozyme) Ribosome.

The diagram above shows the overall formation of the initiation complex, complete with a tRNA (the yellow structure with a pink circle attached). Again, the function of this replication complex is to find the start codon and set the reading frame for the Ribosome. Notice that large ribosomal subunit (60s in eukaryotes) only attaches after AUG has been found.

Elongation
The polymerization of amino acids occurs during elongation. This is where the P and A sites become important (NOTE: P and A sites are the active sites of the enzyme). P stands for Peptidyl, while A stands for Aminoacyl. These are chemical terms, and discuss the orientation of the amino acid. The exit site, represented by E, is not an active site. Consider it a disposal point for spent tRNAs.

During elongation, when you have a filled P and A site, the amino acid from the P site will be linked to the amino acid in the A site. Refer to the following illustration:

The amino end of the amino acid is free. The carboxyl end is attached to the tRNA. Starting at the top, the growing amino acid chain is attached to a tRNA in the P site. A new tRNA with an aminom acid (charged tRNA) is brought into the A site. Using GTP, the Ribosome (large subunit) takes the growing peptide chain and links (carboxyl to amino) it to the individual amino acid in the A site. When this is done, the entire ribosome shifts downstream to the next codon (the new codon appears in the A site).

The spent tRNA that started in the P site is now moved to the E site, where it is removed from the ribosome. NOTE: It takes 2 GTP to create the peptide bond, then another GTP to move the ribosome. So a total of 3 GTP are used in one 'round' of Ribosomal action. REMEMBER THIS!

This process of adding amino acids will continue until a STOP codon is reached.

Statement: To charge a tRNA, you must use an ATP to first phosphorylate the amino acid.

Question: How much ATP will you need to expend to make a protein with 100 amino acids? How about a 150 amino acid protein?

Termination
To create a functional protein, translation must end with the appropriate amino acid. If translation stops to soon, the protein will be to short and many not bend (configure) correctly. If it is too long, then it may not bend (configure) correctly. Termination is there for an important process.

In eukaryotes, a releasing factor is used to seperate the ribosomal subunits.

Once completed, proteins can be further modifed as fits their function (such as adding sugars).

Daily Challenge:
IN YOUR OWN WORDS describe the process of translation. Discuss initiation, elongation and termination. Make sure that you discuss the P and A site, as well as the importance of the start and stop codon. Afterwards, give a BRIEF discussion of the importance of proteomics to modern research.

Wednesday, March 28, 2012

Daily Newsletter March 28, 2012

Today's Topic:
Codons and Anticodons Translation is the process of "reading" mRNA, and using the code to construct a protein. But what is the code? The nucleotide language of mRNA can be divided into codons. Three sequential nucleotides that represent a genetic (nucleotide) word.

In the image below, you have have sequential nucleotides divided up into codons. Notice that AUG is listed as Codon 1. This is important! AUG is the Universal Start Codon. Nearly every organism (and every gene) that has been studied uses the three ribonucleotide sequence AUG to indicate the "START" of protein synthesis (Start Point of Translation).

As we will see tomorrow, it takes more than a start codon to initiate transcription. The start codon sets the start point.

The start codon established the Reading Frame for translation. From the start codon, every three sequential nucleotides will be viewed as a codon. This is critical! Mutations can affect reading frames. For example, if a nucleotide as inserted between codon 2 and 3 (G G), would you have the same reading frame down stream? What is you deleted the first nucleotide of codon 4? What is the effect of changing the reading frame? What would happen to the resulting protein?

Insertions and deletions can change reading frames, but point mutations can also occur. In this case, one nucleotide is change to a different nucleotide. What would happen if the final nucleotide of condon 3 were changed to a C? To an A? How about the second nucleotide in codon 4? Change the U to an A, what happens?

Each codon is a "genetic word", and can be translated into a specific protein. The tRNA is the agent of translation. On one end of the tRNA, you will find an anti-codon. Anti-codons are complimentary to codons. Example: Codon 1 reads AUG. The corresponding tRNA would have an anticodon reading UAC. (Question: Would these be antiparallel?). Codon 2 reads ACG, so the anticodon would read UGC.

An amino acid can be attached to the free 3' end of the tRNA. There is a class of enzymes capable of attaching an amino acid to a tRNA: Aminoacyl tRNA Synthetase. Below is a very basic cartoon of how an amino acid is added to a tRNA.

Note that an ATP is needed to complete the binding. There is an Aminoacyl tRNA Synthetase for each tRNA-Amino Acid combination.

Below is a diagram showing the pairing of codon to anticodon. The diagram also contains a version of the Genetic Code table, showing the relationship between codon and amino acid.

Note that three codons are referred to as STOP codons: UAA, UAG, and UGA. These are used to terminate translation; they indicate the end of the gene's coding region. What would happen if you lost a Stop codon?

Daily Challenge:Genetic Code
In your own words, describe the genetic code and how codons/anticodons work to relate the genetic code to amino acids. Discuss what can happen if the coding sequence is change by either changing, adding or deleting a nucleotide.

Tuesday, March 27, 2012

Daily Newsletter March 27, 2012

Today's Topic:
Transcription Translation is the genetic process where a single strand of DNA acts as a template for the construction of a complementary RNA strand. Generally when talking about transcription, we will be talking about the formation of messenger RNA (mRNA), which carries the code for one gene to a ribosome where it is translated into a protein.

DNA holds the "permanent" copy of the genes needed to make a functional organism. Think of DNA as a locked safe where you hold all your company's blueprints, patents and documented procedures. You don't want to loose these, or risk that they might be changed. You only bring them out to make copies of them, then they go back to the safe. This is what happens with your DNA. You keep it tightly locked up (in a double-helix that is coiled around histones, and then possibly supercoiled), and open it up only when you NEED to make a copy. Notice how NEED is highlighted? Do you think it might be an important concept?

In eukaryotic DNA every gene starts with a promoter. This is a sight of ~8 nucleotides visible in the major groove of DNA. The transcription complex recognizes this sequence as a "START" indicator. The main core of the transcription complex will be RNA polymerase. This enzyme works to build a strand of RNA complementary to DNA. The name polymerase indicates that it is involved with dehydration synthesis polymerazation reactions (taking one nucleotide, and adding it to a growing chain of nucleotides). Like DNA polymerase, RNA polymerase builds in the 5' to 3', and builds phosphodiester linkages between nucleotides.

But RNA polymerase can not act alone. In eukaryotic systems, initiation factors are needed to recognize the promoter region, and then to correctly align the RNA polymerase. Below is a great picture showing the initiation complex and the RNA polymerase II holozyme (RNA polymerase II with all associated protein structures).

As you can see, TATA Binding Protein (TBP) is the first structure to attach to DNA. It recognizes the TATA sequence in the major groove of the DNA double helix. It then forces the the DNA to bend, and acts as a signal to other enzymes directing interactions with DNA. A cascade of reactions occur to then produce the Preinitiation Complex, which ensures that the transcription complex is positioned correctly over the Transcription Start Site, and begins the unwinding (sometimes referred to as denaturation) of the double helix. The Transcription Complex then begins to read the template strand of DNA, and makes an RNA copy (Elongation).

NOTE: Elongation works due to base complementarity. Ribonucleotide triphophates are brought into the transcription complex, and are added to the free 3' end of the growing RNA strand.

Termination: We are not going to spend a lot of time on termination. There are a couple different models of eukaryotic transcription termination. The main feature is that there is a signal sequence of deoxyribonucleotides in DNA that signals the end of transcription.

mRNA processing: Once transcription is complete, in eukaryotes, the RNA needs to be processed. The following is a quick reference for mRNA processing:

5' capping: To protect the mRNA from ribonucleases (RNA degrading enzymes) that attack the 5' end, 7-methylguanosine is added to the 5' end. Usually, the 5' ribonucleotide is replace by this compound. Additionally, methyl groups can be added to the sugar-phosphate backbone to further protect the mRNA.
Polyadenylation: In maturing RNA to mRNA, a poly-A tail is added (usually after cleaving off a small section of the 3' end). This process adds ~250 adenyls to the 3'end of the molecule. This is needed to stabilize the molecule and facilitate export through the nuclear pores. As mRNA is translated, the poly-A tail gets shorter. When short enough, the mRNA is degraded. Thus, the polyadenylation (poly-A tail) is responsible for setting a time limit to the mRNA.
Splicing: The RNA is composed of both coding (exon) and non-coding (intron) regions. To mature into mRNA, the introns have to be removed, and the remaining exon spliced together. This job is the responsibility of the splicosomes.

The above image is a quick reference to the effects of splicing.

The above image is a quick reference to the effects of the splicosome.

Once RNA has been processed (matured), it is ready to be used in translation (protein synthesis).

Daily Challenge: Transcription In your own words, discuss the process of transcription, and the formation (maturation) of mRNA. Remember that we have focused on eukaryotic transcription. Briefly, how does prokaryotic (specifically bacterial) transcription differ from eukaryotic transcription?

Monday, March 26, 2012

Daily Newsletter March 26, 2012

This week, we move into the Central Dogma of biology (molecular biology to be specific). This is the concept of how genetic information is used to produce the functionality of the cell. We also describe this as Gene Expression. It can ultimately be summed up into one statement: DNA makes RNA which makes Proteins.

The two core genetic processes are Transcription (synthesis of RNA) and Translation (the synthesis of proteins).

Today's Topic: Ground rules for the Central Dogma.

Before digging into each process, let's talk a little about what is at stake here. DNA holds our genetic history. It holds codes on how to build an organism, but what does that really mean?

As we saw at the start of the semester, phospholipids can naturally form bilayers. They can even form spherical structures that create two fluid compartments, outside vs. inside.

Membranes though are passive. As a selectively permeable barrier, only certain materials can cross. Proteins add functionality to the membrane. By embedding proteins, you can chance the permeability of the membrane. This is how cells balance what is on the inside, and what is on the outside. Membrane proteins can also have enzymatic or signal functions. Proteins add functionality to the membrane.

A common expression is that DNA holds the code to make an organism. The meaning of this phrase lies in the concept that by making proteins, we make phospholipid membranes functional. From here we can produce metabolic pathways, produce various chemical compounds, anchor with other cells, and in multicellular complex life, we even have the development of special cellular roles that work together to form a composit whole.

The concept of how we go from DNA to RNA and then Proteins is one of the most critical concepts in biology.

As these are genetic processes, there are a few key phrases and terms you need to start remembering:

All genetic processes work because of base complimentarity. (why?)
Gene:

Sometimes referred to as a unit of heredity.
It is a segment of DNA that holds the code for how to make a protein.

In modern biology, we some times refer to a gene product.
A gene product could be either a protein or a functional RNA.
Functional RNAs don't code for proteins; instead, they have some function in cellular metabolism.
Examples of Functional RNA are tRNA, rRNA and snRNA.

A gene holds the code for a gene product (RNA or Protein), but it is more than just the code.
All genes have non-coding sites that are critical for correct transcription (Genes will be copied into a molecule of RNA).
The promoter of a gene is a sequence of DNA nucloetides that indicate the "start" point of a coding region.

In Eukaryotic cells, a common promoter is a DNA sequence that reads TATAAA.
This is known as the TATA-Box.
This sequence is found in the major grove.
The Initiation Complex of Transcription recognizes this sequence in a major groove, and builds the replication complex at this site.
The replication complex will transcribe the gene.

Many genes are regulated, meaning they can be turned on or off.

A regulated gene will have an Operator region between the promoter and the coding region.
This is referred to as being down stream from the promoter.
Regulatory proteins can bind to the operator, preventing transcription.

House keeping genes produce products that are needed for the general function of the cell.

House keeping genes in Eukaryotes would include genes for Glycolysis and the Citric Acid Cycle, but also the genes for Ribosomes and tRNA.
These genes are always ON.
Genes that are always on are referred to as constituative genes.

Messenger RNA (mRNA) is a molecule of RNA that carries a gene code to a Ribosome in order to produce a protein.
The code on mRNA is in Nucleotide Language, being made up of sequences of Ribonucleotides (A, U, G, C).
In order to make a protein, there needs to be an agent of translation.

An agent of translation must be a molecule that contains both ribonucleotides and an amino acid.
A specific ribonucleotide sequence must directly correspond to an amino acid.
This is the basis of the Genetic Code.
The agent of translation is Transfer RNA (tRNA).
In tRNA, there is a direct correspondance between a ribonucleotide sequence (anti-codon) and an amino acid.

We will discuss more about the codon-anticodon later in the week.
Amino acids are added to the 3' end of the molecule. (why there?)

The ribonucleic language is divided into 64 3-letter words known as codons.

The anticodon of the tRNA matches to codons on mRNA.
In this way, we have a direct relation of a codon in mRNA to a protein on tRNA.
There is redundancy in the genetic code (some amino acids can be identified by multiple different codons).

The above diagram is a rather unique way of viewing the genetic code. Your book has another version of the code based on a square table.

Daily Challenge: Central Dogma
Your challenge today is just to discuss the concept of the Central Dogma. Don't worry about mechanisms yet. Consider the implication of the central dogma. In your own words, express why it is important. What are the important features? You can use questions above in "Today's Topic" as a way of focusing your thoughts.

Friday, March 23, 2012

Daily Newsletter March 23, 2012

Evolution Friday Challenge: After going through cell division, explain how our understanding of Meiosis supports Mendel's Laws of Inheritence. From there, explain how Mitosis and Meiosis are important to the development and maintenance of diversity within a species. Finally, how is this system advantageous to what occurs with prokaryotic organisms, like bacteria?

Summer Courses:

I'm offering a topics class this summer (BIOL 4930, CRN 53880). The focus of the course is to read current books in popular biology, and then using journal articles, go through the science. The course is by consent of the instructor, and I'm willing to have students who complete this course join the topics class this summer. In student led discussions, you'll be teamed up with upper classmen or graduate students.

For post-baccalaureate students:
Dr. Errol Reiss, a retired CDC mycologist, is teaching a course in Medical Mycology. Again, this is by consent of the instructor. If you would like to try this class, come and talk to me.

Thursday, March 22, 2012

Daily Newsletter March 22, 2012

Today's Topic: Meiosis

On Tuesday, the topic discussed was mitosis. We saw that mitosis was standard nuclear division. When coupled with cytokinesis, we saw that the goal was taking one parental cell and creating two identical daughter cells.

With meiosis, we will again experience nuclear division, but with a different goal than mitosis. The goal of meiosis is to produce gametic (reproductive) cells. As such, we will 'always' couple meiosis with cytokinesis.

Goal of Meiosis: From one diploid parental nuclei, generate four genetically unique haploid nuclei.

Goal of Meiosis-Cytokinesis: From one diploid parental cell, generate four genetically unique haploid cells.

The production of gametic cells requires two nuclear division events: a reduction division, and an equatorial division.

Important Note: All forms of nuclear division have the same basic four stages. Prophase is the set-up, Metaphase is when chromosomes align, Anaphase is when chromosome/chromatid seperate, and Telophase is when the nucleus returns to "norm".

The reduction division occurs in Meiosis I, and as the name implies, we are "reducing" something. Specifically, we are reducing chromosomal number. REMEMBER: a diploid organism (2N) carries two copies of each chromosome. During a reduction division, the copies are separated and moved to opposite sides (poles) of the cell.

Homologous Chromosomes: This term refers to the two copies of each chromosome. For example: Chromosome 1 in humans is the largest of the chromosomes. Individuals have two copies of chromosome 1: one from their mother and one from their father. These two individual examples of chromosome 1 are considered homologous. Homologous chromosomes carry the same genes, but each homolog (one copy) will have a unique set of alleles (one allele for each gene).

The important part of Meiosis I is what occurs in Prophase I.
During Prophase I, homologous chromosomes are brought together. The homologs possess DNA sequence similarities, and are able to bind to each other. This results in a cross-over event (recombination). During cross-over, alleles are swapped between the two chromosomes, with the end result being genetically unique allele patterns on each chromosome.

This event is one of the most critical ways that eukaryotic organisms ensure the diversity of their populations. Why?

Daily Challenge: We have discussed the main stages of nuclear division, and you have readings from your textbook and supplemental reading on meiosis. In your own words, describe the process of meiosis, complete with a discussion of synapsis, chisamata, and cross-over. Why is the recombination event so critical to population diversity?

Wednesday, March 21, 2012

Daily Newsletter March 21, 2012

Reading:
The Eukaryotic Cell Cycle
This is an excellent overview of the cell cycle. This is considered supplemental to what is in your textbook.

Today's Topic: Cell Cycle and Regulation

The cell cycle describes the life stages of a cell. It starts just after cytokinesis, and continues until the next cytokinetic event. The period when a cell is growing between division events is known as interphase.

Interphase is divided into three distinct steps: G₁ Phase, S Phase, and G₂ Phase.

The G₁ Phase stands for Gap 1 Phase, and begins just after cytokinesis. Gap here refers to no visible change in the cell. Another good term for G is growth, and that is usually what happens during this phase. The cell is building primary products; compounds such as amino acids, phospholipids, carbohydrates, triglycerides. Usually there is an increase in cell size as well. A major goal in this phase is the development of biomass.

When the cell gets a signal to divide, the physiology of the cell changes. Metabolic pathways for creating deoxyribonucleotides are unlocked (dATP, dTTP, dGTP, dCTP). The cell will use these deoxyribonucleotides to synthesize DNA (Replication). The production of enzymes needed to replicate DNA will also be begin.

During the S Phase, cellular metabolism is focused on DNA replication (S stands for DNA Synthesis). This is a complex event, takes time, and has consequences if there is an error; so most of the cells work is dealing with DNA replication.

Once S Phase has begun, the cell has committed its self to the process of Nuclear Division and Cytokinesis. You never replicate DNA without moving toward Nuclear division, DNA replication without nuclear division usually results in cell termination.

After DNA replication, the cell needs to build all of the proteins and compounds used during Nuclear Division and Cytokinesis. This is the goal of the G₂ Phase. The G₂ Phase will continue until the required components are constructed, and the cell receives the signal to continue. At this point the cell moves into the M phase (which stands for either mitosis or meiosis).

Regulation,
The processes of the cell cycle is tightly regulated.
What happens in unregulated or uncontrolled cell growth?

The regulation is based on Signals (yes, we're back to signals). To maintain homeostasis, an organism must replace certain cells during its life time. For instance, humans replace skin and mucous membranes constantly. Hormones, such as insulin-like growth factors, are signals used to make sure the body maintains its self by replacing cells.

Inside of cells, there is an internal signal system based on the protein family Cyclin Depdendent Kinases (CDK). Note, this is a family of proteins involved in cell cycle regulation (they also have a few other functions). As the name implies, the protein needs a Cyclin to function. For example, CDK2 requires Cyclin E during G₁.

CDKs are always produced in mitotically active cells. (What term do we use for a protein that is always produced?) Cells don't always have Cyclin, but instead produce them in response to a signal.

Throughout the cell cycle, there are time points referred to as Check Points. These check points are where regulation occurs. For example, to move from the G₁ Phase to the S phase, you need to produce a set of cyclins to induce the activity of CDKs. The Cyclin-CDK complexes can then phosphorylate proteins. Why would you need to phosphorylate proteins?

During the G₁ Phase, the check point determines if you turn on the production of deoxyribonucleotides and the production of replication complex enzymes. There are check points in the G₁ Phase, S Phase, G₂ Phase, and M Phase. Many of these check points are determinations of the health of the cell, or the correctness of DNA replication and chromosome condensation.

G_o Phase
Some cells become non-mitotic at a given point in development. For example, nerve cells stop dividing, as do cardiac muscle cells. When a cell becomes non-mitotic, it shifts from the G₁ Phase to the G_o Phase. The cell can be locked from mitosis by blocking the genes for either CDK or Cyclin.

Daily Challenge: In your own words, describe the cell cycle. Then answer the following question: How are CDKs related to cancer?

Tuesday, March 20, 2012

Daily Newsletter March 20, 2012

Today's Topic: Nuclear Division

Mitosis describes nuclear division. We commonly use the term loosely to describe cell division, but that is an incorrect usage of the word Mitosis. Cell division is better described by the term cytokinesis. It is important to use these terms correctly, as it will help you as you go further through biology.

Mitosis describes a nuclear division event. Most of the time we think of nuclear division occuring just prior to cytokinesis (cell division), but there are examples of cells that can undergo nuclear division without undergoing cytokinesis (many fungi do this). For most eukaryotic cells though, mitosis will be followed by cytokinesis. Remember though that these are two different events.

Mitosis is also described as somatic nuclear division. The word somatic refers to general body cells. This is to contrast difference between a general cell and a reproductive cell. A reproductive cell, or gametic cell, will undergo a special type of nuclear division known as meiosis, which will be discussed in Thursday's newsletter.

The goal of mitosis is to produce two daughter nuclei that are genetically identical. So when we couple mitosis and cytokinesis, the goal is to create two genetically identical daughter cells.

Going into mitosis, DNA replication will have had to occur. Every molecule of DNA will have undergone replication (DNA synthesis). We will discuss the process of DNA replication in class on Thursday.

The process of mitosis occurs in 4 Main Phases (there are additional phases that have been added in recent years). Below is a phrase to remember:

"Prophase sets up the process, metaphase aligns the chromosomes, anaphase seperates the chromosomes, and telophase returns the cell to normal."

This phrase describes the basic action of the four main steps: Prophase, Metaphase, Anaphase and Telophase.

Review the University of Arazonia's Mitosis Tutorial. This will take you through the main phases, and includes the Prometaphase addition.

In Prophase, we see the condensation of the chromosomes, which were discussed in yesterday's newsletter. We also see the dissolution of the nuclear envelope and the formation of the mitotic spindle.

In Prometaphase, microtubules of the mitotic spindle reach toward the centromere of each chromosome, forming the kinetochore.

During Metaphase, the chromosomes are aligned down the imaginary equitorial line of the cell. This line is equidistant between the centrioles. The alignment is important. If you look at most drawings, the chromosomes are shown as aligning so that their centromeres are on the equitorial line, and individual chromatids are on either side of the line. This is to represent an equitorial division. As each sister chromatid of a chromosome represents a complete DNA molecule, the division of these will result in an equal number of chromosomes on either side of the equitorial line. So, a cell with 46 molecuels of DNA (chromosomes) will produce two dauther nuclei (and then cells) with 46 moledules of DNA (chromosomes).

Beyond showing the arrangment of chromosomes, the image above also shows the different types of microtubules: Kinetochore, Polar and Aster. Aster, meaning star (Greek), comes from the starlike appearance of these microtubules. This starlike arrangment is also seen in the plant genus Aster, which is noted for the radial startlike flower petals. Note: they are sometimes referred to as Astral microtubules (Astral is an English adjetive derived from Aster).

Once the chromsomes have been arranged, they can be seperated. Anaphase is when there is visible seperation of the chromosomes into daughter chromatids. This link to an Anaphase Image is an excellent reference for what occurs in Anaphase (remember that you have motors that can move down microtubules).

During Telophase, the cell returns to normal interphase operation. The mitotic spindle will be released, the nuclear envelope will reform, and the DNA will be released from the supercoiled packing that produced the chromatids and chromosomes.

Study Note: You will notice that above I gave you a number of links. Do you think that they are important for your overall understanding of this topic?

Remember This: The following phrase will help you as we move through genetics. Remember it!

"Base complementarity is the foundation of all genetic processes."

Daily Challenge: Mitosis
Describe the process of mitosis in your own words. Feel free to use images, just reference where you got the image. Remember that this leads to your milestone paper and exam, spend some time to build a personal description of mitosis.

Special Announcement:

It's Spring

Monday, March 19, 2012

Daily Newsletter March 19, 2012

Video Special: In honor of St. Patrick's Day, here is a little biology video for you. Can you identify and describe all of the processes the signer is describing?

Today's Topic: Chromosomes
Before we discuss DNA and cell division, let's talk a little about chromosomes. A chromosome is a single molecule of DNA with associated packaging proteins, and is visible only during Metaphase and Anaphase of nuclear division.

We use the term chromosome to refer to a single molecule of DNA, but remember, in the strict sense, it only refers to a visible arrangement of DNA and proteins seen during nuclear division.

Another loose use is referring to the single, circular DNA molecule found in bacteria (or other prokaryotic DNA). As bacterial DNA is not held by the same packaging proteins, and has different packaging issues, the use of chromosome in this case is in error. The term genophore is a more appropriate term.

In eukaryotes, DNA must be packaged. One reason for this is to prevent physical strain or damage to the DNA molecule. The second reason is to conserve space. DNA is just too large when it is not packaged. The basic unit of DNA packaging is nucleosome. The nucleosome is a unit of packaged DNA, in which the DNA molecule is wrapped 1.67 times (~147 base pairs) around a core of 8 positively charged histone molecules (positive charge attracts negative phosphates).

These histone cores, when associated with Histone₁ can begin to supercoil into a fiber. A cascade of interactions causes more supercoiling which ultimately forms the chromosome.

The chromosome when it first forms during prophase of nuclear division is actually two freshly replicated molecules of DNA (we just copied DNA). Below is a picture of an individual chromosome:

Notice that the two sides of the Chromosome are individual DNA molecules that we refer to as Chromatids. Holding the two chromatids together is a protein rich region known as the centromere. At the centromere, we will find a molecular motor known as the kinetochore. We will see the operation of the kinetochore during cell division.

Here is a video to help you visualize the process:

Daily Challenge:
In your own words, describe how DNA is packaged into a chromosome. Why is it important that we package DNA at the nucleosome and chromosome level?

Other resources:

Administrative Note: Milestone Paper 2
You have until tomorrow night (March 20th) to finish the review process.

Friday, March 16, 2012

Daily Newsletter March 16, 2012

Today's Topics: Beyond Mendel
As discussed in class yesterday, after the rediscover of Mendel's work, people began investigating inheritance in other systems. As research continued, scientists began seeing that the Mendelian ratios did not always work. There were variations.

Sex linked traits: Many species have what is known as a sex chromosome. Normally, every chromosome of a given set is the same size and shape, and most importantly, they carry the same genetic information. Not so with sex chromosomes. One variation of the chromosome is shorter, and does not carry the same information. When the standard and shorter chromosome (X and Y) are in the same cell, you have a Hemizygotic state. The suffix hemi come from ancient Greek, and means half. This refers to the idea that some of the genes in an XY pairing are haploid, not diploid. If the X has a gene that the Y does not possess, then it is always expressed (as would be the case in haploid organisms).
Epistasis: Epistasis involves a two gene system. While the genotype follows Mendelian Laws, the phenotype does not. The reason is that one gene completely masks the effect of the second gene. Below is an epistatic example. Can you describe how this is different from a standard dihybrid cross?

Pleiotrophy: This is when an allele has widespread impact in an organism, and so is not limited to one trait. For example, would a change in microtubles affect only one aspect of a cell? Would it affect only one cell type? Pleiotrophy may also cause problems at different stages of development, such as varying affects at different ages. Here is an example of pleiotrophy.
Heterosis: Hybrid Vigor. Inbreeding can depress the adaptive strength of a species by allowing recessive traits a greater chance to express. When you begin crossing inbreed strains, you suddenly see an increase in adaptive vigor. This is useful with coordinated breeding of animals and plants, as the hybrid produced is stronger than the parental strains. It also informs our understanding of endangered species, and helps researchers work on ways to increase not only the adaptive vigor an an endangered species, but also the population size (without increasing inbreeding depression).
Gene expression from environmental cues: Some genes are only triggered during certain environmental conditions. Remember the concept of signal pathways and signal transduction. The body picks up an environmental signal, and then tells the cells to change in some way. There are two terms you need to understand when dealing with Environmentally Cued Gene Expression:

Expressivity: This describes how much gene expression you get in an individual when exposed to the proper cues.
Penetrance: This is a population concept. When exposed to a given condition, how many individuals of the population express the gene?

Some additional reading for those interested in genetics:

Daily Challenge: How do variations in Mendelian genetics provide adaptive strengths to a species? For example, how would epistasis aid a species?

Administrative Note: Please go into the peer review application (SWoRD) and double check the paper you have loaded. Some students have noticed that what they uploaded turned into gibberish (symbols and numbers).

If this has occurred, go back to your original document. Resave your document in Rich Text Format (rtf). You can do this by clicking "SAVE AS", and then scroll down the options of file types. Select Rich Text Format. Upload the paper. This will solve the problem of papers being converted to gibberish.

Wednesday, March 14, 2012

Daily Newsletter March 14, 2012

Daily Topic: Independent Assortment

Yesterday we talked about inheritance of one trait. Today we look at two different traits that are held on different chromosomes.

Mendel was again lucky. The traits that he looked at were found on different chromosomes (DNA molecules). The math would have been horrible if they had been on the same chromosome! Luckily, Mendel did not seem to have to worry about that.

With the Law of Segregation, Mendel showed that for each individual trait, a pea plant (and by extension a human) has two possible allele that they can carry for a single trait (gene). When ovum and sperm (pollen) are produced, the parent donates only one allele to the ovum or sperm; the parent donates only one allele to the next generation. Therefore a new individual is composed of a set of genes (and alleles) from the mother, and another set from the father.

So, what happens when you look at two different traits (genes)? Ultimately, what Mendel discovered is that the two different traits do no interfere with each other. An allele from the first gene is donated independently, and uninfluenced by, the allele from the second gene. So, you have a 50/50 chance of donating a given allele from the first gene, and a 50/50 chance of donating an allele from the second plant.

The math get's a little harder, but the idea is the same. The easiest way of showing what happens is to look at the Punnet Square for a visual interpretation of the probabilities. Below is a great picture of a Punnet square:

As you can see, on the top we put the Male Genetic Donation, and on the left side we put the Female Genetic Donation. There is a 50/50 chance the male will donate a given allele, same with the female. Look at how this is represented. Male donation is either B or b. Each has its own column. For the female, each possible donation has its own row. You then just cross-reference column and row to find out the possible offspring. The Punnet square also provides a rapid visual. 4 possible offspring, 3 of which are purple.

The Punnet square can be expanded to look at a dihybrid cross (two traits). Below is a good image of a dihybrid Punnet square, with the offspring ratios included:

Daily Challenge:
Explain the concept of Independent Assortment. I made a point that this does not always occur when genes are on the same chromosome. So, what happens to Independent Assortment when genes (traits) are on the same chromosome? Why is it important?

Administrative Note: Paper
There is confusion regarding the Due Date. I have said tonight, but I have included in the system a "Late" period which will last until Thursday Night. You will not be penalized if you get the paper in during the "Late" period.

Tuesday, March 13, 2012

Daily Newsletter March 13, 2012

Today's Topic: Mendel's First Law of Genetics
To understand Mendel, we must first understand some terms and put them into context.

Gene - A segment of DNA that holds a sequence of nucleotides that provide the instructions on how to create either RNA or a Protein. These are known as gene products.
Chromosome - This is a molecule of DNA and associated proteins. The chromosome is only visible during specific phases of nuclear division. The word chromosome is used loosely (weak sense) as a synonym of DNA.
Haploid - A cell that has only one copy of each DNA molecule (chromosome).

NOTE: each organism has a known number of DNA molecules (chromosomes).
Humans have 23 different DNA molecules (23 different chromosomes).

Diploid - A cell that has two copies of each DNA molecule.

Humans have 46 chromosomes total: 2 copies of each of the 23 different DNA molecules.

Mutation - A change in the nucleotide sequence of DNA.
Genetic Variation - Different versions of the same gene generated by mutation. These could be subtle or pronounced alterations.
Phenotype - The specific physical form an individual's genetics produces. Generally we start by looking at one well defined physical trait, such as flower or seed color.
Allele - Genetic Variation in a single gene that results in different phenotypic expression.

There can be many different genetic variations in a population.
An individual can only possess a number of allele equal to the # of chromosomal copies.
So, a human is diploid, possessing 2 copies of each gene.
Humans can therefore have at most 2 alleles for each gene.
A haploid individual has only 1 allele for each gene.

Genotype - The specific alleles an individual possesses for a given trait.

Mendel's work with the garden pea, Pisum sativum, resulted in two laws of inheritance. The focus of his work was to determine the inheritance pattern of specific traits. For example, if you have a pure breeding strain that produces white flowers, and a pure breeding strain that produces purple flower, what is the percentage of offspring which will possess purple flowers?

His work was based on probability mathematics, and as we have discussed previously, mathematical certainty is needed in the establishment of laws.

Mendel's First Law is known as the Law of Segregation. Remember, Mendel did not know about genes or even DNA. He was working solely with gross physical characteristics that could be observed with the naked eye.

Going back to flower color, Mendel first wanted to see what would happen if you took pure-breeding white flowered peas and crossed (mated) them with pure-breeding purple flowered peas. Many of Mendel's contemporaries held the view that the offspring were produced by a blending of characteristic. What Mendel saw directly contradicted this view. He saw only purple flowers.

Mendel decided to self-cross (self-pollinate) this generation of purple flowers. The next generation held both purple and white flowered individuals, but in a very specific ratio - 3:1. He repeated his experiment, and even used different characteristics. The same thing happened: pure-breeding parents produced offspring with a specific trait, and when self-crossed, these produced offspring in which the original parental traits appeared in a 3:1 ratio.

Mendel inferred the following from his mathematical calculations:

Each individual possesses two "factors" which determined the specific trait, e.g., Flower Color.
When an ovum or pollen is produced, it holds only one Factor.
When an ovum and pollen join, the new individual will carry one factor from the ovum (mother) and one factor from the pollen (father).

Today, we understand more regarding the mechanism which Mendel inferred. Mendel's factors are genes, and alleles describe the differences between factors.

But why did the offspring of the pure-breeding plants produce only purple flowers?

Mendel was lucky. The traits he picked had variations based on a mutation of a single gene. Today we would also call the mutations here as knock-out mutations. The purple color is produced by a fully functional gene. It produces a functional pigment. The white color is produced because the gene that codes for the pigment is flawed; it can't produce the pigment. What you have is one functional gene product (dominant) that masks a non-functional gene product (recessive).

Genetics become much more murky when you have multiple genes coding for a trait or when you don't have a complete knockout

Daily Challenge: Using one of Mendel's genetic models, other than flower color, describe his experiment and the law of segregation.

Administrative Note:
Administrative Note: The Website for Milestone 2 will be open later today. You will receive a special notice regarding the new website when it is ready to accept papers.

Monday, March 12, 2012

Daily Newsletter March 12, 2012

Administrative Note: Upon the recommendation of a colluege, you are going to try a different peer review service. You will be given an opportunity after this review to comment on which you found more useful and esier to use.

More information about the service will come when the site opens after 5pm tonight. You will have until Wednesday night to upload your papers. You can continue to review until Sunday night (you must review all papers given you to).

Today's Topic: Gregor Mendel and Probability
Today I want you to look at the history of Gregor Mendel and his legacy. In addition, I want you to become more familiar with probability theory and its application. Use the links below for more information and guidance.

Biography of Gregor Mendel - A good overview found at the National Health Museum.
Mendel Museum of Masaryk University - Interesting links, including pictures of Mendel's garden (restored from original).
The Nine Lives of Gregor Mendel - An interesting look at different perspectives of Mendel's work.
Gregor Mendel and the Principles of Inheritance - A good overview of Mendel, with a nice summation of his legacy.

Probability Tutorial From West Texas A&M.
Probability Tutorial at ThinkQuest sonspored by Oracle Education Foundation.

The probability tutorials serve as a refresher. I'm not asking you to be an expert in probability theory, just that you have a good concept and foundation of probability theory. It will help as we work through Mendel's work.

Daily Challenge:
For today, I want you to create a brief profile on Gregor Mendel. Talk about his life, his work and his legacy. What can you learn from Mendel? This question is not about his work in genetics, but more about his scientific technique. If Mendel were here today, what could you learn from him? What guidance would you seek? Also consider and reflect upon the idea that it took decades for his work to become known. Why was that? What affect did it have when people saw it? Consider the impact of his work on science and society? Do we use Mendel's concepts in general society?

Friday, March 9, 2012

Daily Newsletter March 9, 2012

Daily Challenge: Last week, you were asked to look at the evolution of metabolism. We're going to continue this today. Now having looked at plant based photosynthesis, and variations on plant based photosynthesis, discuss the evolution of photosynthesis an metabolism. Which would have come first? How would early organisms gain the required reducing potential? How would early organisms gain biologically available carbon? What is the importance of Rubisco? What is the importance of having a photosystem that can use water to regenerate needed electrons (and give off oxygen)?

Consider these questions, and then write up your impressions.

Wednesday, March 7, 2012

Daily Newsletter March 7, 2012

Today's Topic: Carbon Fixation

One of the most important reactions in biology is the carbon fixation step of the Calvin Cycle. As discussed in lecture, there are other forms of carbon fixation found in bacteria, but when it comes to the global supply of bioavailable carbon, this the the main player.

What is the global supply of bioavailable carbon? Consider what you ate today? Did it consist of starches, vegetables, animals? Did it have protein, carbohydrates, lipids? These are all biomolecules derived from this initial reaction. You may have heard that all of our energy comes from the sun; well it is this reaction that converts solar energy into biological compounds.

Above is a great diagram of the carbon fixation step in the Calvin Cycle. CO₂ is added to the second carbon. Remember, there is an unstable intermediate that is formed, which spontaneously splits into 3PG.

Ribulose 1,5 Bisphosphate Carboxylase (RuBisCo) is the enzyme that catalyzes the carbon fixation step. This enzyme is often cited as the most abundant enzyme on the plant, which is most like the case. No one though could doubt that it is the single most important enzyme, for without this, we would not have the quantity of organic carbon that is needed to support life as we know it.

Daily Challenge: The Calvin Cycle
Discuss the stages of the Calvin Cycle: Carbon Fixation, Redution of 3GP, and Regeneration of Ribulose 1,5 Bisphosphate. Include in your discussion of the reduction of 3GP how 2 G3P is converted to glucose.

In class I discussed the complexity of the regeneration step. The image below shows the route to the regeneration of Ribulose 1,5 Bisphosphate. The top of the picture deals with carbon fixation and reduction of 2GP. the rest shows the regeneration steps.

For your blog, if you would like, go through the steps and see if you can explain what is happening. What is required is that you show an understanding of the major stages of the Calvin cycle; going through the individual steps though could aid your understanding.

Learning Objectives: It should be obvious from class and this newsletter that learning and understanding the carbon fixation step is critical. What of the rest of the Calvin Cycle? Do you need to memorize the rest of the cycle?

Tuesday, March 6, 2012

Daily Newsletter March 6, 2012

Today's Topic: Photosynthetic Energy Harvesting

The chloroplast of the the plant has two know Photosystems: P680 (Photosystem II) and P700 (Photosystem I).

Photosystem II

Used to Generate ATP (chemiosmosis)
Water is split to recharge the P680 reaction center with electrons and hydrogens.
Donates electrons to Photosystem I

Photosystem I

Can operate either Cyclic or Non-Cyclic
Non-Cyclic

Excited electrons are given to NADP⁺
Electrons accepted from Photosystem I to recharge the P700 reaction center.

Cyclic

Excited electrons are used to make ATP (chemiosmosis)
Electrons are returned to Photosystem I (recycled) to recharge P700 reaction center.

Remember: The photosystems are complex arrangements of chlorophyll pigments found in the thylakoid membrane. When electrons are used to make ATP, the electrons will be passed between electron carriers that act as proton pumps. The electrons are used to build and maintain a proton motive force, which will directly be used to make ATP. So all electron movement is occurring due to electron carriers in the membrane.

Daily Challenge:
Describe how the photosystems work to produce ATP and NADPH + H⁺. Remember with Photosystem I, you have both cyclic and non-cyclic operation.

Monday, March 5, 2012

Daily Newsletter March 5, 2012

Administrative Note: There are two notes today.
1) This is a milestone week. Check your calendars.
2) We have passed the midpoint of the semester, and this is when a planned change is to occur. You will notice that each news letter has guiding comments or questions to help you build your own Learning Objectives for this week.

Today's Topic: Photosynthesis
In photosynthesis, the cell will generate reducing power by using a photon to excite an electron. You will recall from chemistry that that electron excitation when an electron jumps to a higher energy state (a higher shell).

Photoexciation is one of the principle ways to excite an electron, and we can do this in a modern lab fairly easily. In nature though, you require a structure that can "focus" the photon's energy. Chlorophyll provides such a structure. As a pigment, the structure of chlorophyll is built to absorb specific wavelengths of light, and then excite a set of electrons.

Note that at the center of the chlorin ring is a Magnesium ion, which can be considered the focal point of the photoexciation.

Chlorphylls are arranged in systems, and once photoexcitation has occurred, the energy is transferred by resonant energy transfer to a Reaction Center.

The reaction center is formed by a pair of chlorophyll molecules. There are two specific reaction centers known in plants, the P680 and P700. These names refer to the maximum red absorbance wavelength for these two molecules. The P680 reaction center is found Photosystem II, while P 700 is found in Photosystem I.

NOTE: The photosystems were named in the order that they were discovered.

The reaction centers gather the energy absorbed by the surrounding chlorophyll. These reaction centers then undergo a charge separation, which is a form of redox reaction that donates high energy electrons to a waiting quinone. The image below is of photosystem II.

There are a few important points in this image:
1) Notice in the center there is a group f structures with the code Pheo. This represents a Phenophytin, which is a chlorophyll without the magnesium in the center.

The paired chlorophylls become a paired phenophytin. This change (loss of the magnesium) is a where the absorbed energy is converted to a redox potential. The energy is handed off to a quinone (Q).

2) When we discussed respiration, we discussed Ubiquinone, which is an example of a quinone. The quinones are electron carriers within the membrane. The quinones take the harvested reducing potential to electron carriers for processing.

3) Photosystem II has a way to recharge the system with electrons and hydrogen. The reaction center of photosystem II has the hydrolytic ability; it can break water. The hydrogens, and their electrons, join photosystem II, recharging the reaction center (they convert pheophytin back to chlorophyll). In the process, they release oxygen (O₂).

The harvested electrons will be used to either make ATP (chemiosmosis) or to reduce NADP⁺ to NADPH + H⁺.

Today's Challenge: Explain in your own words how photon energy is harvested and converted into reducing power.

Learning Objectives:
What is the focus of today's discussion? That should be one of your learning objectives.
There were some highlighted words. Do you think those would be important?
We discussed photosystems and reaction centers; are they important?
P680 and P700 refer to the absorbance of a wavelength of light; are electromagnetic wavelengths important for this topic?

This week, we will meet on Tuesday March 6, 2012. We will focus our discussion in the beginning on the topic of converting photon energy into reducing power, and how the overall plant responds.