Mendelian Genetics Part no. 1 - Defining Key Vocabulary

Solving Mendelian genetics problems can seem somewhat daunting from the onset, especially with the vocabulary that is associated with them. Here we will define key terms that are used in genetics problems, but also, walk you through the proper steps needed to come up with the answer.

Part no. 1 will be concerned with vocabulary and define all the appropriate terms needing to understand Mendelian genetics. Part no. 2 will show examples and explain how to set up and solve problems. 

Vocabulary

1. Gene - A gene is a sequence of DNA, which is made up of nitrogenous bases (Adenosine, Thymine, Cytosine, and Guanine or A, T, C, and G). This sequence codes for what ultimately will become a protein in the cell. We know that proteins have many jobs throughout the cell, so these genes code for functional proteins, or proteins that have specific roles in the cell.

2. Allele - This term can be confusing to the novice trying to learn genetics. An allele is simply, an alternative version of a gene. For instance, if a gene codes for hair color in an organism, then there might be alleles for brown hair, blonde hair, etc. Alleles are determined by the genotype, which will be defined below.

3. Dominant - Dominant traits are those which mask a recessive trait. In genetic notation, we use letters to denote whether an allele is dominant or recessive and the dominant allele will be represented by a capital letter in the genotype. An example might be Aa or Bb with the dominant allele in bold and the recessive allele not.

In an example of the effects of a dominant trait masking a recessive one, the allele for brown eyes  (B) masks the allele for blue eyes (b). So, using the letter B for our gene, our genotype of Bb would result in someone with brown eyes, even though the allele for blue eyes is present. This is an example of True Dominance. We will go into further detail regarding this subject matter.

4. Recessive - Recessive traits, as mentioned above, are masked by dominant traits. They will not be expressed if a dominant allele is present. However, the exception is if there are 2 recessive alleles inherited, such as aa or bb. In this instance, the recessive phenotype (physical trait expressed by genes) would be expressed.

5. Genotype - This is the allelic combination for a particular gene. As previously noted, genotypes are made up of alleles, which are simply alternative version of genes. So for a gene concerning eye color, we might have an allele for blue eyes (b) or brown eyes (B). In this event, our genotypes might be BB, Bb, or bb.

The first genotype (BB) would have brown eyes expressed. The second genotype (Bb) would also have brown eyes expressed because brown eyes is dominant to blue eyes, which is represented by a capital letter B. However, the last genotype (bb) would express blue eyes because there are no dominant alleles to mask the blue color. As a result, this person would have blue eyes.

6. Phenotype - The phenotype is simply the physical expression of the genotype, as we described above. If a genotype is BB, then the phenotype will be brown eyes. If the genotype is Bb, the phenotype will be brown eyes, as well. If the genotype is bb, then the phenotype will be bb.

7. Homozygous Dominant - This term refers to the makeup of the genotype and whether the letters in that genotype are all capital. The stem 'homo' means same, 'zygous' refers to having zygotes, and dominant comes to mean the same thing we have been using it for, being that it masks the allele that is recessive (if one is even present). In this case, however, homozygous dominant genotypes will be of the variety AA, BB, or CC. All organisms with this genotype will show the dominant phenotype. This genotype can be referred to as true breeding.

8. Heterozygous Dominant - Just like the Homozygous Dominant genotypes, Heterozygous Dominant genotypes also mask the recessive alleles. In this type of genotype, there is a recessive allele present, but it is masked by the dominant allele. The stem 'hetero' means different, so the genotypes will be in the form of Aa, Bb, or Cc. This type of genotype is also referred to as a hybrid.

9. Homozygous Recessive - This type of genotype will have 2 lowercase letters and will express the recessive phenotype because there is not a dominant allele to mask the recessive alleles. The genotype will be in the variety of aa, bb, or cc. This type of genotype is also known as true breeding because they have the same 2 alleles for the genotype.

10. Punnett Square - This is a box divided into smaller squares that is used to cross (mate) 2 genotypes together, with the goal of determining their possible offspring. Below an image is pictured.

Prokaryotes vs Eukaryotes

While eukaryotic cells and prokaryotic cells have some characteristics in common, they diverged from their common ancestor billions of years ago, thus accounting for significant differences in overall structure and function. Here we will go over them.

1. Presence of a Nucleus- Eukaryotic cells have a true nucleus. This means that the genetic information in the form of DNA is protected by a membrane called the nuclear membrane. This is NOT the case with prokaryotes, which lack this nuclear membrane and instead have their genetic information jumbled up in what is known as the nucleoid (resembling a nucleus).

2. Chromosomes- Eukaryotes have true chromosomes. True chromosomes are compact forms of DNA that are wrapped up with the help of proteins. And not only do they have chromosomes, but they have many chromosomes, which take on a linear (straight) conformation. Prokaryotes on the other hand do NOT have true chromosomes, only have one 'chromosome', which happens to be circular in nature.*

*Prokaryotes do have other genetic elements present in their cells including things called plastids, but they will be reserved for discussion in another blog.

3. Presence of Telomeres- Before differentiating between the presence of telomeres, it is important to know what these structure are. The telomeres are structures at the end of linear chromosomes (those found in eukaryotes). Their function is to keep the chromosomes from being degraded by particular molecules/compounds in the cell. Because prokaryotes have circular chromosomes, here is no need for them. This is why they are only present on eukaryotic, linear chromosomes.

4. Presence of Cellular Organelles- Organelles are like small organs in a cell that work together to accomplish tasks within the cell. Eukaryotes contain many of them that prokaryotes simply don't. These include lysosomes, peroxisomes (both involved in digesting molecules within the cell), microtubules, endoplasmic reticulums, the golgi apparatus, mitochondria, and chloroplasts.

5. Ribosome Size- Ribosomes are the locations in which proteins are made for the cell or for shipment out of the cell. While both eukaryotic and prokaryotic cells do contain ribosomes, they are different in their sizes. Prokaryotic ribosomes tend to be dramatically smaller than eukaryotic ribosomes.

6. Mitosis- Prokaryotes do not undergo mitosis when dividing, but instead undergo another process of budding off called binary fission. Eukaryotes do however, undergo mitosis to divide it somatic cells.

7. Cell Size- The size of these two types of cells is also a dramatic difference. Eukaryotic cells can be 10 to 100 times bigger than prokaryotes at a size of 10-100 micrometers. Prokaryotes tend to be in the range of 1-10 micrometers.

8. Cell Type- Eukaryotic cells are known as multicellular because they work together with other types of cells to form an organism. Prokaryotic cells are dubbed unicellular because these types of organisms are simply made of 1 cell. 

9. Types of Organisms- Eukaryotes include plant and animal cells, while prokaryotes include the kingdoms Bacteria and Archaea.

10. Other differences include the composition of their flagellas, which take on a different structural build; the cell wall compositions, which can be found in both plant (eukaryotic) cells and prokaryotes; the components of their cellular membranes; among others.

A quick note on some of their similarities include the presence of vacuoles, cell walls, flagellas, ribosomes, genetic information (DNA/RNA), and vesicles.

Krebs Cycle Broken Down

The Krebs cycle, also known as the Citric Acid cycle, is a very important process in cellular respiration. Without this portion, respiration would not be possible. This is because the Krebs cycle uses the pyruvate molecules from glycolysis to produce high energy molecules essential for the electron transport chain (ETC) which follows soon after. Here we will go over the different processes that occur during the Krebs cycle, breaking it down molecule by molecule.

FUNCTION: To produce high energy molecules such as NADH and FADH2, which act as electron carriers in the electron transport chain. The ETC is where most of the cell's ATP (energy currency) is produced. Additionally, many different precursor molecules are made that can be utilized by a cell.

The Krebs cycle is what is known as Amphibolic, in that it is both catabolic (breaks down molecules) and anabolic (builds molecules).

LOCATION: Mitochondrial matrix

NET PRODUCTS: 2 GTP, 6 NADH, 2QH2 (ubiqinone), 2 FADH2, 2 CO2, minimal ATP

Step 1. Pyruvate molecules (3-carbon) from glycolysis are converted into another type of molecule called Acetyl-CoA in a process known as pyruvic oxidation. This conversion occurs when the pyruvate is broken down by an enzyme, releasing a carbon atom which goes on to form carbon dioxide (CO2). The 2 remaining carbon molecules bond with coenzyme A forming Acetyl-CoA. During this process, electrons and a hydrogen ion are passed to NAD+, thus oxidizing the pyruvate, hence the name of the process.

Step 2. The Acetyl-CoA then enters the Krebs cycle. It initially combines with a 4-carbon molecule called oxoaloacetic acid, forming a 6-carbon molecule of citric acid (citrate). This reaction is catalyzed by the enzyme citrate synthase.  Upon this formation, the coenzyme A is released.

Step 3. The citrate molecule is then dehydrated (H20 molecule is removed) and then rehydrated by the the enzyme aconitase. The resulting molecule is just a rearranged form of citrate known as isocitrate.

Step 4. Next, isocitrate undergoes what is known as a oxidative carboxylation, which simply means that a carbon and hydrogen are given off. The result of this is a 5-carbon molecule called alpha-ketoglutarate. This process is catalyzed by the enzyme isocitrate dehydrogenase. Additionally, the carbon that broke off forms CO2, while the hydrogen reduces NAD+ to form NADH.

Step 5. In the next reaction, alpha-ketoglutarate has yet another carbon molecule removed and is then transferred to a CoA molecule by the enzyme alpha-ketoglutarate dehydrogenase. The resulting product is a 4-carbon molecule of Succinyl-CoA. Additionally, CO2 and NADH is formed.

Step 6. After succinyl-CoA is formed, the molecule then undergoes the removal of the CoA carrier, resulting in the production of succinate. Additionally, the enzyme succinyl-CoA synthetase that removes the CoA also produces GTP through substrate level phosphorylation (phosphate molecule directly added to another molecule). GTP is a high energy molecule similar to ATP.

Step 7. Next, succinate is dehydrated by the enzyme succinate dehydrogenase. The resulting product is furmate.

Step 8. Furmate is then hydrated by enzyme furmase to form malate.

Step 9. Lastly, the malate is dehydrogenated by the enzyme malate dehydrogenase, forming the original molecule oxaloacetate. From this reaction, NADH and H+ are also produced.

Once the oxaloacetate molecule has been regenerated, the Krebs cycle can repeat. With the completion of this cycle, the electron transport chain (ETC) and subsequent oxidative phosphorylation occurs, resulting in the production of 36-38 ATP, providing the cell with energy.

Renin-Angiotensin-Aldosterone Made Simple

The body has many systems that work together in order to maintain homeostasis. The renin-angiotensin-aldosterone pathway is no different. It has 3 functions: (1) to maintain a proper blood pressure/blood flow, (2) to maintain the right concentration of sodium (Na+) in the blood, and finally, (3) to maintain the right amount of water in the blood. To make sure that these 3 things stay at proper levels, several hormones and several organs work together to accomplish this task. Now to break the pathway down!

RENIN-ANGIOTENSIN-ALDOSTERONE PATHWAY

This process starts out in the kidneys, but becomes very systemic (all over body) throughout the pathway. It does return to the kidneys at several instances. 

1. Low blood pressure/blood flow is sensed by the Juxtaglomerular apparatus in the kidney (which are cells next to the glomerulus). This is because a decrease in Na+ will reduce the amount of water in the blood, thus the blood will have a lower pressure. This follows the principle of osmosis, which states that water will diffuse to areas that have highly concentrated solutes.

2.  In response to this, the glomerulus  (the bed of capillaries that is wrapped up by Bownan's capsule and is next to the proximal convoluted tubule) releases a hormone known as renin into the blood stream.

3. Renin then moves to the liver, where is converts an inactive peptide (protein) angiotensinogen to an active angiotensin I.

4. Angiotensin I then travels to the lungs where an enzyme known as the Angiotensin Converting Enzyme (ACE), converts Angiotensin I to Angiotensin II. One effect Angiotensin II has on the body is in its ability to constrict blood vessel, thus increasing blood pressure. Another function of it is to stimulate the adrenal glands on top of the kidneys to produce the hormone Aldosterone.

5. Aldosterone stimulates the reabsorption of sodium (Na+) in the distal convoluted tubules. Increasing sodium reabsorption means that water and chloride (Cl-) will follow, thus increasing blood volume.

6. An increase in blood volume may also trigger the release of a hormone known as Atrial Natriuretic Hormone, which inhibits the release of Aldosterone, keeping the body's water and sodium levels at the homeostatic levels.This last step is known as a negative feedback loop.

And that is the renin-angiotensin-aldosterone pathway. If one can grasp the concept of osmosis and how water follows highly concentrated solutes, one will be able to understand blood pressure and other methods of osmoregulation (water balancing) in the kidneys.

Drunken Monkey Hypothesis

Craving a beer? Feeling bad about it because you think you might be addicted to alcohol? Don't feel bad because all humans are addicted to alcohol...here's why. According to the 'Drunken Monkey Hypothesis', proposed by Dr. Robert Dudley of the University of California- Berkeley, human beings are actually attracted to ethanol (the type of alcohol we drink) because of their huge dependence on fruit throughout our evolutionary journey. Fruit, contains ethanol, and our body craves it as if we were still foraging for food. Along with this hypothesis is our desire for sugars and fats. Why you ask? For the same reasons, however, it is a two-fold answer. Firstly, sugars and fats are very high in calories, fats to be exact are worth twice as many calories as proteins. While proteins are better for us nowadays, if one of our ancestors was able to get double the energy to survive thousands of years ago, that was the better option (obviously). Also, fats and sugars were a whole lot more rare than they are today, so that coupled with the fact that we could gain more energy from these 'horrible' items, over time, ingrained a desire in our genes to crave sugar, fats, and alcohol. So whenever you feel bad about drinking, blame your ancestors of thousands of years ago.

Opposites Attract

I'm sure everybody has heard the saying 'opposites attract' in reference to a multitude of different things, whether that be magnetic charges, animal interactions, etc. Well, research over the last decade or so has come up with actual evidence for this being the case, not only in non-human relationships, but also in human relationships. The basis for this claim rests in the quest for organisms to have stronger, more diverse DNA, which for the most part, results from more exposure to varying nucleotide sequences. There is a complex found in animals (as well as, humans) called the major histocompatibility complex (MHC), which participates in cell recognition, as a major component of the immune system. It is also well known that there are harmful, deleterious effects that occur from mating between family members. This of course has a high probability of hampering offspring development. Due to these deleterious effects resulting from interbreeding, there is actually evidence from studies that people and other animals instinctively (built in from evolution) seek out mates (more so on the female's part because it deals with when they are in a fertile state). What is the way they do this you ask? Through pheromones. Without getting too into the specific details, the DNA and subsequent proteins, code and function in producing representations of the MHC and other DNA components in the form of pheromones that the males and females secrete. The secretions are sensed so that the females and possibly males (in some other form) can seek out a mate, all in an effort to diversify their DNA for evolutionary stability purposes.

FOOD FOR THOUGHT: Other pheromones that females secrete out of the arm pits, are responsible for the alignment of menstruation cycles with women living in a house together for a extended period of time. The pheromones are sensed by glands in the nasal cavity, which send these signals to the brain via an efferent nerve. The brain then determines when the menstruation occurs. Another evolutionary stable move, because animals that have young at the same time, with other animals they are close to, can help raise the offspring, thus reducing the fitness cost (ex: lionesses carrying for cubs that are not theirs).

Oceans Frozen 900 Ft. Global Warming You Say?

Over the last several years, biologists have been trying to figure out the chemical compositions of the primeval Earth (ancient Earth), as well as, when organic matter began to take control and produce life. When the Earth was first created, it was a giant hot ball of molten elements, that had a reducing atmosphere (meaning the atmosphere was composed of gases such as NH3-ammonia, CH4-methane, H2-elemental hydrogen, CO2-carbon dioxide, among others). In this case, life would have been very hard to get started, until better conditions arose. The important thing to realize was that it did, and the earth eventually cooled down -- maybe froze would be a better word. When looking at the carbon distribution in the Earth, biologists originally thought that it was mostly in the atmosphere as carbon dioxide (CO2), which would create the so called 'Greenhouse Effects' that are supposed to be causing global warming , today. When CO2 is in the atmosphere, it works as kind of a blanket to keep heat in. So, in the case of the Earth, the earth would have not cooled down as fast....OR DID IT? New theories are coming out saying that most of the carbon at this time was in fact not in the atmosphere as CO2, but in the ground as calcium carbonate (CaCO3). Due to the sun being about 70% as powerful as it is today, the earth with no greenhouse effects, would be super COLD! So cold that the whole world would have oceans that were frozen 900 + ft down! Sounds like it would be a challenge to ice fish, but at least it would have been safe to skate!