Biofoundations Unit 4

Genes and Inheritance (1-40) Gene Expression (41-104)

Mitosis and Meiosis are the ________ of ________

mechanisms of inheritance

What is heredity?

The transmission of physical form parents to offspring

What is a phenotype?

Any observable characteristics of an individual

What are some examples of traits, in individuals and cells?

• Individuals - large scale observable features like height, eye colors, or hair texture

• Cells - the kinds of sugars it can use to make ATP, what kind of electron acceptor it uses, does it make a receptor for a certain hormone

What are polymorphic traits?

Traits with multiple forms

What is a phenotype?

The specific version of a trait that an individual has

Ex: The possible phenotypes for fur color in Labrador Retrievers

True or False: The specific traits and phenotypes of an individual come from the collective action of that individual’s genotype

True

What are genes?

A region of the DNA of a chromosome that contains the info needed to produce a protein or RNA molecule

True or False: Most traits are monomorphic bc most genes of a species exist in multiple

False; most traits are polymorphic bc most genes of a species exist in multiple forms

What are alleles?

Multiple versions of a gene

What is cystic fibrosis and why is it a genetic disorder?

• Cystic fibrosis – a genetic disorder that primarily affects the lungs 

• Originates in one gene and has two alleles 

• One allele produces a normal functional protein and one allele produces a protein that gets trapped in the endoplasmic reticulum 

What happens during Cystic Fibrosis?

• The cell of the lung normally produces a saline solution needed to allow our lungs to clear and remove mucus

• This saline solution is made by a transporter protein in the plasma membrane called CFTR

• In ppl w/ Cystic Fibrosis, the CFTR protein does not fold properly into its 3D shape, and this misfolding traps it in the endoplasmic reticulum, and blocks the production of saline

• This causes mucus to becomes trapped and causes frequent and sometimes life-threatening lung infections

On what chromosome is the CFTR gene on? and what are the alleles on that gene?

• CFTR gene is found on human chromosome #7 

• There are two alleles: “normal” CFTR (F) and “misfolded 
   CFTR (f) 

What is a genotype?

The specific combo of alleles that any one individual has

Fill in the Blank: Because our cells are _____, we have two copies of each chromosome, one from ____ and one from _____. Each person carries __ ______ for each gene.

• Diploid

• Mom

• Dad

• 2 alleles

So what does diploidy mean? And give an example

• Diploidy - 3 possible genotypes

• 3 Possible Genotypes for CFTR:

1. FF: “normal” CFTR on both chromosomes

2. Ff: One “normal” and one “misfolded” CFTR

3. ff: “misfolded” CFTR on both chromosomes (Cystic Fibrosis result)

What is the difference between dominant and recessive Alleles?

• Dominant Alleles (capitalized letter) - only one copy needs to be present for its phenotype to be expressed

• Recessive Alleles (lowercase letter) - both copies need to be present for its phenotype to be expressed

What does it mean when we say that both alleles are the same on a genotype? (both are either capitalized or lowercase)

Homozygous genotype

What is the difference and outcome between homozygous dominant and homozygous recessive?

1. If both are dominant then we say it is homozygous dominant 

• The individual will have the phenotype of the dominant allele 

2. If both are recessive then we say it is homozygous recessive 

• The individual will have the phenotype of the recessive allele 

What does it mean when we say that both alleles are the different on a genotype? (alleles are either capitalized and lowercase)

In a genotype, if both alleles are different we say that genotype is heterozygous 

In a heterozygous genotype, which allele will always determine the phenotype of the individual?

The dominant allele

What is gain of function?

where the mutation or allele has enhanced or new function that persists regardless of the presence of a normal allele 

What is loss of function?

where a mutant allele decreases or eliminates a protein’s function 

What is the difference between haplosufficiency and haploinsufficiency?

• Haplosufficiency - If one allele can make enough of the normal protein to maintain normal function  

• Haploinsufficiency - Dominant loss of function  

What are the two things Mendelian genetics allow us to do?

• Predict the genotypes and phenotypes of the offspring of two parents 

• Also use the genotypes and phenotypes of the offspring to predict the genotypes of the parents

How do Mendelian Genetic principles and rules come from the way chromatids are separated in meiosis?

• Each gamete gets only one copy of each chromosomes are therefore only one of the possible alleles 

• The allele that each gamete receives is randomly chosen due to independent assortment 

In a punnet sqaure, what is the difference between the genotypic and the phenotypic ratio?

• Total up the different genotypes to determine the genotypic ratio 

• The percentages of traits produced is the phenotypic ratio 

Exceptions to Mendel’s Genetic principles: True or False: Genes only have two alleles or traits

False

• Not true: sometimes, genes can have multiple dominant alleles, multiple recessive alleles, or both 

• Not True: sometimes alleles of a gene can be neither dominant nor recessive and produce more than two traits 

How would ABO blood types be an exception to Mendel’s assumed principle that genes only have two alleles?

• Blood types come from a single protein that is found in the plasma membrane of red blood cells and these proteins have several sugars attached to them in a long chains called glycoproteins

• These sugar chains are built by an enzyme called ABO glycosyltransferase that exists in 3 different versions 

• The gene for this protein is called I and has 3 alleles that make up Type A, B, O

• This system has a genetic property called codominance 

• Genes w/ co-dominance have multiple dominant alleles that do not blend their traits 

• The gene for this protein called I and it has two dominant alleles and one recessive allele

• W/ their alleles there are 6 possible genotypes and 4 possible phenotypes 

Exceptions to Mendel’s Genetic principles: True or False: Sometimes dominant and recessive traits blend tg

True; this is called incomplete dominance

Exceptions to Mendel’s Genetic principles: Why is sickle cell anemia a product of incomplete dominance in the genes?

• Sickle cell anemia – genetic disease caused by variations in the gene for hemoglobin

• Two alleles for hemoglobin gene 

• Hemoglobin A (HA) - functions normally 

• Hemoglobin S (HS) - forms unusually long chains that distort the shape of red blood cells which forms a curved or sickle shape 

• Three posssible genotypes and phenotypes 

1. H^AH^A (homozygous dominant) - person ahs normally functiong hemoglobin 

2. H^SH^S (homozygous recessive) - person has sickle cell anemia 

3. H^AH^S (heterozygous) – person has a condition called sickle cell trait 

• The curved blood cells Become trapped in blood vessels which can cause pain and swelling and Are easily destroyed in the blood vessels, causing the person to have fewer rbcs than they need (anemia) and fatigue 

• In sickle cell trait: The rbc make both types of hemoglobin (a blended trait), Red blood cells will typically function normally and only a few sickle cells are made (normal hemoglobin is dominant), However, an acute attack of symptoms can happen called sickle cell crisis (usually only w/ extreme physical activity under stressful conditions) 

Exceptions to Mendel’s Genetic principles: Fill in the Blank: _______ is when the effect of one gene can be altered or hidden by another

Epistasis

Exceptions to Mendel’s Genetic principles: In some ppl who have a type A or type B genotype, their blood type is not either of those types, but instead type O (how does ABO blood groups use epistasis?)

• The sugar chains on a rbc are made by a metabolic chain of enzymes and Types A B and O are due to the last sugar added to that chain 

• The gene for the enzyme in the chain directly in front of I is H 

• H has two alleles: The dominant H allele makes an enzyme that functions normally and add the H sugar and The recessive h allele makes an enzyme that cannot add the H sugar 

• The I enzyme requires the H sugar to be added to function normally 

• In ppl who are homozygous dominant for H or heterozygous the enzyme adds the H sugar correctly so the I enzyme can add the A or B sugars normally 

• In ppl who are homozygous recessive for H, the enzyme does not add the H sugar 

• Now the I enzyme cannot add A or B sugars so an hh individual will always have type O blood no matter what their I genotype is 

Exceptions to Mendel’s Genetic principles: Sometimes variations in a single gene can change the development of multiple traits. What is this called?

Pleiotropy

Exceptions to Mendel’s Genetic principles: How is sickle cell a product of pleiotropy?

The sickle cell phenotype is a single genetic change that causes multiple changes in systems throughout the body like skin and eye damage, blood clots, high blood pressure, heart disease 

Exceptions to Mendel’s Genetic principles: What are polygenic traits?

When complex traits arise from the action of multiple genes

Exceptions to Mendel’s Genetic principles: How is human height an example of polygenic traits?

• Development of human height is influenced by at least 10k known genetic alleles 

• Polygenic traits typically develop according to a normal distribution  

• Normal Distribution (Bell Curve) – the average is most commonly found in individuals 

• As you move up or down in either direction that traits become progressively more rare

Exceptions to Mendel’s Genetic principles: True or False: Sometimes, environmental factors contribute to the development of a trait 

True

Exceptions to Mendel’s Genetic principles: How do environmental factors lead to development of a trait?

• Genetic alleles explain only abt 80% of the variations we see in human genetics/DNA 

• The other 20% is explained by the influence of the individual’s environment like: Availability of food and other nutrients, Lvl of physical activity, Exposure to environmental pollution 

Exceptions to Mendel’s Genetic principles: How can environmental effects happen in single traits?

• Enverinoment effects can happen in simple traits to 

• Siamese cats have a variant allele in the genes that determine coat color 

• The enzyme that makes the dark color of their fur is called tyrosinase 

• Tyrosinase is sensitive to temperature 

• In the cooler parts of the body, the tyrosinase enzyme is active and those parts become dark 

• In the warmer parts of the body, the tyrosinase enzyme is inactive and those part stay white 

For all organisms, where do their traits directly come from?

The expression of the genetic instructions in the cell’s DNA

Fill in the Blank: In genetics, we use the generic term ______ to describe all of the genetic instructions contained w/i a cell or virus

genome

Fill in the Blank: Chromosomes and other genetic material (like plasmids) are made up of many individual instructions called ______

genes

What is the function of genes?

Each gene is a set of instructions for making one or more proteins or RNA molecules

What is gene expression?

The process by which the info encoded in a gene becomes a functional product of a cell or organism

Why is it important for us to understand gene expression?

• The traits and functions of an organism is based on the set of structures they have and the functions their cells can perform 

• The structures a cell has and the functions it can perform are determined by the set of proteins that their genome carries instructions to make 

• In order to understand how cells function we must understand how those genetic instructions become proteins and how those proteins perform their functions in the cell 

True or False: In order for cells of all types to stay alive and perform the necessary functions of life they must turn the instructions in their DNA into proteins

True

True or False: Protein’s aren’t really that important in cells

False; proteins are responsible for forming most of the structures and carrying out most of the functions in life in cells

What is the central dogma?

The set of rules by which govern the process of how DNA becomes a protein

What are the types of RNAs?

• Messenger RNA (mRNA) 

• Transfer RNA (tRNA) 

• Ribosomal RNA (rRNA) 

• Other non coding RNAs 

What is the general process of the central dogma?

• Genetic info needed to make all of the proteins of the cell is stored in the sequence of the DNA molecules of the cell’s genome 

• Info stored in a gene’s DNA sequence is copied into an RNA sequence using the process of transcription 

• Info transcribed into an RNA sequence is used by the ribosomes of the cell to make a protein using the process of translation 

What is transcription?

Transcription - copying the info stored in DNA into an RNA molecule 

How does transcription work?

• DNA base pairs are temporarily separated by breaking the hydrogen bonds 

• Genetic sequence in DNA is read from beginning to end 

• As it is being read, a copy of that sequence is made using the rules of complementarity 

What enzyme performs transcription?

RNA polymerase

What are the types of RNA polymerase?

• RNA polymerases 1 (Pol 1) - inn nucleus (nucleolus), makes some ribosome components 

• RNA polymerase 2 (Pol 2) - makes mRNA 

• RNA polymerase 3 (Pol 3) - makes some small non-coding RNAs 

What does RNA polymerase do exactly in transcription?

• RNA polymerase slides along the DNA molecule, reading the genetic sequence of one strand to make an almost exact copy of the opposite strand 

• The strand that is read by the RNA polymerase is the template strand 

• The strand that will be copied is called the coding strand 

True or False: Bc RNA polymerase does not use base T (thymine) in its copies, and uses Uracil (U) instead, it is not almost exact 

True

True or False: Complementarity works exactly the same in DNA and RNA. In DNA: A pairs w/ T, G pairs w/ C and in RNA: A pairs w/ T and G pairs w/ C

False; Complementarity works differently in DNA and RNA. In DNA: A pairs w/ T and G pairs w/ C. In RNA: A pairs w/ U and G pairs w/ C

Fill in the Blank: RNA molecules made during transcription by RNA polymerase are called ______.

mRNA

Where is mRNA made?

• Prokaryotic cells - cytoplasm

• Eukaryotic cells - nucleus first then mRNA is transported into the cytoplasm (in picture)

What happens once mRNA is in the cytoplasm?

Once in the cytoplasm, that genetic RNA message is grabbed by a ribosome which uses it to make a protein 

Proteins are what?

Long chains of amino acids

What are the types of bonds that hold each amino acid tg?

peptide bonds

True or False: a typical protein is a chain of amino acids group

False; a typical protein is a chain of hundreds of amino acids

What is a protein sequence and why is it so important?

• If we were to read the order of amino acids in a protein, that is called its protein sequence 

• The information to make this protein sequence is stored in the genes of our chromosomes  

True or False: Each single protein has the same protein sequence

False; each single protein has a unique protein sequence

Fill in the Blank: The genetic sequence of an RNA molecule is organized into 3 letter words called ______

codons

Since each of these codons corresponds to a particular amino acid in the protein sequence, what are rules that define which amino acid corresponds to each codon?

Genetic code

Why are methionine (MET) and STOP codons special?

• Methionine (AUG) - codon that tells the ribosome where to start translating the mRNA 

• STOP codon – tells the ribosome when the protein is complete and to translating 

What is the part of the cell that does the translation?

Ribosome

How does the ribosome translate? What does it need?

• Ribosome slides along an mRNA molecule and reads the codons of the genetic sequence and creates the new protein chain 

• Requires special helper RNA molecules called tRNA (transfer RNA) 

• tRNA will form base pairs w/ the mRNA which allows it to carry the correct amino acid into the ribosome Requires 

What are the systems of control of gene expression?

1. Chromatin Remodeling – the cell can regulate how tightly or loosely chromatin is packed 

2. Transcription Control – the cell can control the timing and volume of transcription of individual genes 

3. RNA Processing – after transcription, RNA must be modified before it exits the nucleus 

In cells, what is DNA found as and how many do humans have and what are the functions of it?

• In cells, DNA is found as one more extraordinarily long double-stranded molecules called chromosomes 

• In humans: 23 pairs of chromosomes, two sets each, so 46 total chromosomes per ell 

• In humans, total length of all chromosomes ins a 3.2 billion base pairs 

• Approximately 20% of chromosomal DNA are genes called Coding DNA 

• Remaining 80% has a variety of functions, much of which is still unknown as non-coding DNA 

True or False: Even w/i a single gene, there are DNA sequences that do not directly code for an RNA or Protein 

True

What does the image represent? This is the genetic sequence for insulin

• Parts in purple represent the sequence that contain he genetic code for insulin protein (Exons) 

• Parts in Black will be removed from the RNA before it leaves the nucleus, (introns) 

What is the coding region of a gene?

The coding region of a gene begins at the transcription initiation site 

True or False: The coding region of a gene is the same as the start codon

False; the start codon is where RNA polymerase starts transcription starts, while the coding region is where exon and intron sequences will alternate as we move along the strand

True or False: there is several types of regulatory DNA sequences

True

Fill in the Blank: ________ ________ ________ allow the cell to exercise transcriptional control over individual genes

DNA regulatory sequences

What are the gene sequences that are used by RNA polymerase and its helper proteins to bind to the DNA for transcription

Core promoter

What are the helper proteins for RNA polymerase and what do they do?

• The helper proteins for RNA polymerase are called general transcription factors 

• A transcription factor is any protein that is able to bind to dna regulatory sequences and can increase or decrease the rate of gene transcription by RNA polymerase 

True or False: In order to be used by enzymes, DNA must be fully unwound and the base pairing separated. RNA polymerase cannot do this on its own, it needs the general transcription factors to assist.

True

Why is using general transcription factors to assist a super power?

• The successful interaction of all these transcription factors is requried for transcription to happen 

• Bc this is true, the cell can regulate transcription by regulating the interaction of thse proteins 

What does the cell use to regulate the interaction of the general transcription factors and how do they work?

• The cell regulates the interaction of the general transcription factors w/ accessory promoters 

• DNA sequences that either stabilize or interfere w/ the interaction of the general transcription factors w/ the core promoter 

True or False: In eukaryotic cells, most accessory promoters are located near the actual gene and in extrons. Those that are far away are called promoter-proximal elements.

• False

• In eukaryotic cells, most accessory promoters are located thousands of bases away from the actual gene or in introns

• Some are not and they are called promoter-proximal elements

What are the two types of accessory promoters?

• Enhancers – accesory promoters that increase transcription of a gene by stabilizing the general transcription factors 

• Silencers – accesory promoters that decrease transcription of a gene by interfering w/ the general transcription factors

Fill in the Blank: Accessory promoters can also have _______ ________ to them

regulatory proteins

What is the difference between the two types of regulatory proteins that bind to accessory proteins?

• Transcriptional Activator – a protein that binds to an enhancer sequence which stabilizes the interaction btwn the general transcription factors and increase transcription/the amt of mRNA made from the gene 

• Transcriptional Repressor – a protein that binds to a silencer sequence and inhibits the interaction btwn the general transcription factors and decrease transcription/the amt of mRNA made from the gene

Activator and repressor proteins cannot directly interact w/ the general transcription factors (TFs). What must they interact through?

A large protein complex called the Mediator

What must happen for the enhancer or silencer sequences that are far away from the gene must do?

Must form DNA loops to interact w/ the mediator

How does the mediator regulate the transcriptional control?

• If there are more activators than repressors, then the Mediator stabilizes the general TFs and transcription happens 

• If there are more repressors than activators, then the mediator inhibits the general TFs and transcription is blocked 

 

What is the process of translation?

1. The chromatin in the region of the chromosome containing the gene is decondensed 

2. Decondensing the chromatin opens up the DNA and allows accessory TFs (repressors and activators) to bind 

3. DNA loops are formed so that the accessory TFs can bind to and interact w/ the mediator 

4. Mediator interacts w/ the general TFs; activators stabilize general TFs while repressors inhibits them 

What must a transcribed mRNA do before it goes through translation?

RNA processing

What are the 3 types of RNA processing?

1. Capping the 5’ end

2. Polyadenylation of the 3’ end

3. Removal (splicing) of introns

What is the 5’ and the 3’ end made out of and why is it important?

• 5’ cap is made by adding guanosine triphosphate (GTP) 

• 3’ end has a long string of adenine nucleotides called the poly-A tail 

• Capping and Polyadenylation is used for 

1. Nuclear export signal that allows mRNA to exit though the nuclear pore 

2. They prevent the mRNA from being immediately broken down in the cytoplasm 

3. They act as signals that help the ribosome to bind to the mRNA during translation 

Fill in the Blank: Transcription of a gene copies the entire coding region including all _______ and ______. Before the mRNA is ready to be translated the ______ must be removed from the mRNA

• Exons

• Introns

• Introns

What is the processing of removing introns called and where is it done?

• Splicing

• Performed in the nucleus by a structure called the spliceosome

What is the spliceosome built from and what can we call the spliceosome?

• The spliceosome is built from several smaller RNA-containing proteins called snRNPs (small nuclear ribonucleoproteins) 

• Bc the enzyme functions of the spliceosome are dependent on RNA, we call the spliceosome a ribozyme 

How does splicing work?

1. Binding of the snRNPs and formation of the spliceosome on the MRNA causes the formation of an RNA loop 

2. This loop is then cut by the spliceosome at the beginning of the intron 

3. The beginning of the intro is then permanently bonded to the end of the intron at a spot called the branch site 

4. The far end of the intron is cut and the two exons are connect tg w/ a covalent bond 

True or False: Approx 70% of genes can be alternatively spliced (or spliced in multiple ways)

True