2 purines- adenine and guanine

2 pyrimidines- cytosine and thymine

adenine with thymine (A-T)

guanine with cytosine (G-C)

the leading strand grows continuously

the lagging strand grows in short discontinous stretches or okazaki fragments

What is the role of Okazaki fragments?

What is the function of mismatch repair proteins in DNA replication?

What are transcription?

RNA consists of a single polynucleotide strand

the sugar molecule in RNA is ribose rather than deoxyribose

the nitrogenous base uracil (U) occurs in place of thymine (T) and the other 3 bases are the same

How do initiation, elongation, and termination occur during transcription?

Initiation- when RNA polymerase binds to the promoter

Elongation- after binding to the promoter, RNA polymerase begins elongation by adding new nucleotides to the 3' end of the growing RNA molecule

Termination-when elongation stops when RNA polymerase reaches the termination site along the DNA template strand. It constains a specific sequence of nucleotides

What is a promoter in the context of transcription?

the information contained in the nucleotide sequence of the messenger RNA (mRNA) molecule produced by transcription that is translated into amino acid sequence of a polypeptide

it is nearly universal thus virtually all life on the planet uses the same language of evolution

What do the codons UUU, UCU, UCG, CCG, and GGG specify in terms of amino acids?

UUU- Phenylalanine

UCU- Serine

UCG- Serine

CCG- Proline

GGG- Glycine

What do the codons AUG and UAG specify?

AUG-Methionine (start codon)

UAG- stop codon

located in the cytoplasm, sites of translation

consists of 2 subunits. Eurkaryotes- the large subunit contains 3 different ribosomal RNA (or rRNA) molecules, together with about 45 different protein molecules. The small subunit contains one rRNA molecule and 33 different protein molecules

In prokaryotes- ribosomes are somewhat smaller, with different rRNA and protein molecules

 What is transfer RNA and how does it function in translation?

serve as the adapters that link the codons in the mRNA to the amino acids in the polypeptide

The t-RNA molecules are able to bind to amino acids associated with mRNA and interact with ribosomes

For each of the 20 amino acids there is at least one specific tRNA molecule

If the DNA sequence on the template strand is TAG, what is the anticodon, and what amino acid is bound by the tRNA when it is charged?

Initiation- formation of an intiation complex

Elongation- a new tRNA molecule whose anticodon is complementary to the second condon on the mRNA associates with the ribosome. The amino acid of the 1st tRNA is then attached to that of the 2nd tRNA, and the 1st tRNA is released in the cytoplasm

termination-the ribosome encounters a stop codon on the mRNA

What amino acid is the first one in the polypeptide sequence (as specified by the start codon)?

An assemblage consisting of a mRNA molecule with a set of assciated ribosomes and their growing polypeptide chains

*all of the polypeptides produced by a polysome will be identical in sequence

introns- noncoding iternal sequences

exons- one or more introns may be interspersed within the protein-coding regions

it is produced by transcription and produced by introns and exons

What are germ line mutations and somatic mutations?

germ line mutations- those that occur in the specialized cells that give rise to the gametes are key as they constitute the heritable changes in DNA structure.

somatic mutations- occur in other cells of the body may be important to the individual in which they arise but are not passed from parent offspring

What are point mutations? How might they arise?

involves changes in single nucleotides in the DNA sequence are key mechanism by which new alleles are formed at the given gene in a population

May arise because of errors during DNA replication when the incorrect base is inserted into the DNA sequence of the growing strand (when an A is inserted instead of a G)

By what three mechanisms might errors arise in DNA replication, thereby leading to point mutations?

DNA polymerase may insert the wrong base- though proofreading and mismatch repair correct most such errors, some may escape detection

The four bases are somewhat unstable-they can exist in 2 different forms, known as tautomers.

Bases may change because of a chemical reaction- c may be converted to u because of deanimation. During replication DNA polymerase will insert an A rather than a G at the corresponding position in the growing strand

What is the difference between a spontaneous mutation and an induced mutation?

spontaneous muation-arising via one of these B mechanism

Point mutation may also to be induced by a mutagen orignating outside of the cell such as a chemcial mutagen or ionizing radiation that causes a change in the DNA sequence

What are transitions and transversions, and which of the two are typically more common?

Transitions- DNA polymerase mistakenly substitutes one purine (A or G) for another purine, or substitutes one pyrimidine (C or T)

Transversions- if a purine is mistakenly substituted for a pyrimidine or vise versa

transitions are much more common point mutations than transversion when DNA sequences are compared between organisms transitions typically out humble transversion by a ratio of 2 to 1

What is the relationship between redundancy in the genetic code and synonymous mutations?

What are nonsynonymous mutations?

the change in DNA sequence results in an amino acid change

a change in the DNA sequence from GCA to ACA results in a change in the mRNA sequence from CGU to UGU. The former codon specifies the amino acid arginine whereas the latter codon specifies the amino acid cysteine

At which position in the codons do most (but not all) synonymous mutations occur?

At which position in the codons do most (but not all) synonymous mutations occur?

Which types of point mutations are likely to be selectively neutral and why?

Which types of point mutations are likely to be deleterious, and what is their likely fate in terms of selection?

nonsynonymous mutations- the amino acid

Which types of point mutations may be advantageous, and what is their likely fate in terms of selection?

What are two key predictions (or expectations) of the Neutral Theory of Molecular Evolution?

the vast majority of base substitutions that become fixed in populations are neutral with respect to fitness such that genetic drift dominates evolution at the level of DNA sequences

positive selection on advantaegeous or beneficial base substitutions is largely inconsequential in terms of accounting for differences in DNA sequences between populations and species

mutations that arise per generation and are likely to become fixed is constant, with a value equal to the neutral mutation rate. Can you explain why in mathematical terms?

Is there evidence to support the Neutral Theory?

How does the Ka/Ks ratio differ if nonsynonymous substitutions are neutral, deleterious, or advantageous?

neutral- Ka/Ks=1

deleterious- thus subject to negative selection -Ka/Ks<1

advantageous thus subject to positve selection- Ka/Ks>1

What pattern in Ka/Ks ratios did Huttley and colleagues find for the BRCA1 gene in mammals, and what were their main inferences?

the branches connecting chimps and humans to their common ancestor the Ka/Ks ratios are significantly greater than 1 suggesting that the nonsynonymous substitution along those branches have been advantageous thus subject to postive selection

The Ka/Ks ratios are less than 1 for all species pairs suggest that the nonsynonymous substitutions have been largely deleterious. For both genes with the Hawaiian lineage many of the Ka/Ks ratios are greater than 1 sometimes substituting so suggesting that many of the nonsynomous substitution have been advantageous and thus subject to person selection

those that involved in gamete recognition during reproduction and in resistance to diseases. Some ex. include the genes that encode for

1. proteins involved in the self-compatibility system of plants in the tomato family esp in the interaction between pollen tubes and style

2. Din den proteins in sea urchin which are species specific egg recognition

3. Proteins of the major histocompatibility complex or MHC in humans speficially their antigen recognition site . (human immune system)

4. Immunologlobin in humans which are key antibody protein of the immune system

About how many protein-coding genes does the human genome contain?

What is gene duplication (in general terms) and what is its link to the origin of new genes?

exchange of genetic material between non-sister chromotids

unequal crossing over- breaks in the chromatids occurring at different points

Are mutations that arise from unequal crossing over germ line mutations? Why, or why not?

What are transposons and how do they give rise to gene duplication?

transposons- sequences of DNA that have the ability to move from one part of the genome to another (mobile genetic elements)

It makes an RNA copy of itself, which acts as a template for the synthesis of new DNA, which then inserts itself at a new location in the genome. It may replicate adjacent genes (likely to be somatic)

What is polyploidy, or genome duplication?

As discussed in lecture, what are three possible fates of duplicated genes?

1. Both copies of the gene may retain their original function, with the results that the organism may simply produce larger quantities of the encoded polypeptide

2. One copy of the gene may retain its original function while the second copy accumulates mutations that lead to divergence in its function

3. One copy of the gene may be incapacitated by the accumulation of deleterious mutations such that it becomes a functionless pseudogene. (transcription will not occur)

Paralogs- genes that are related to one another through such gene or genome duplication events within a lineage

orthologs- genes found in different organisms that arose from a gene in their common ancestor

Are paralogs evident in the phylogeny for engrailed genes in animals?

What are gene families, and how do they arise?

encode polypeptides of the oxygen-binding proteins myoglobin and hemoglobin

Myoglobin- primary oxygen storage protein

Hemoglobin- carries oxygen in the blood, binding it in the lungs or gills and transporting it to various body tissues

What is the pattern of gene expression for members of the a globin and b-globin gene clusters during human development?

What key inferences derive from the phylogeny of the globin gene family?

What do Hox genes encode?

AIDS has killed 25 million people to date with HIV having infected more than 65 million people worldwide

every day 8,500 people die of AIDS worldwide and 13,400 people are newly infected with HIV

by 2020 AIDS will claim 90 million lives 

Why do we refer to HIV and other viruses as intracellular parasites?

1. RNA genome

2. The enzyme reverses transcriptase integrase and protease

3. A protein coat (or capsid) and 

4 A membrane envelope with surface protein gp120 and the anchoring protein gp 41

What is the function of reverse transcriptase?

synthesizes HIV DNA from HIV's RNA template

What is the sequence of events (in detail) by which an HIV virion attaches to and invades a host cell, then uses the host cell’s enzymatic machinery to reproduce?

1. HIV's extracellular or virion stage

2. HIV's gp120 protein binds to CD4 and coreceptor on host cell

3. HIV's RNA genome reverse transcriptase, integrase and protease enter host cell

4. Reverse transcriptase synthesizes HIV DNA from HIV's RNA template

5. Integrase splices HIV DNA into host genome. HIV DNA is transcribed to HIV mRNA by the host cell's RNA polymerase

6. HIV mRNA is translated to HIV precursor proteins by host cell's ribosomes. Protease cleaves precursors into mauture viral protein

7. New generation of virions assembles inside host cell

8. New virions bud from host cell's membrane

What types of host cells are parasitized by HIV?

destroying virions circulating in the bloodstream and by killing its own infected cells

Helper T cells with the CD4 protein on their surface and macrophages are both crucial to the immune system's ability to destroy virions and kill infected cells, yet these are precisely the cells that HIV targets.

Why does the human immune system ultimately collapse?

HIV 1- primarily responsible for the global AIDS epidemic

HIV 2- less damaging to its host (less virulent) than HIV 1 Individuals infected iwht HIV 2 progress to AIDS but at a slower rate than individuals infected with HIV

What key inferences derive from the phylogeny of SIV and HIV based on the work of Hahn and colleagues, especially in terms of the origin(s) of HIV?

SIV/HIV lineage is monophyletic yet HIV 1 and HIV 2 have different origins within this monophyletic lineage. HIV 2 originated from sooty monogabey SIV. HIV 1 originated from chimpanzee SIV

How did Korber and colleagues assess the timing of the transmission of SIV from chimpanzees to humans, and what key inferences did they draw?

What key factors account for the high mutation rate of HIV?

reverse transcriptase in HIV is error-prone and the HIV genome does not encode any error-correcting enzymes (such as mismatch repair enzymes).

More than 50% of the DNA transcripts produced by reverse transcritase contain at least one point mutation

What is an epitope, and what is the function of the surface protein gp120.

epitopes- short pieces of viral protein displayed on the surface of the virion

Epitopes of the viral surface protein gp120- binds to CD4 and coreceptor on the surface of the host cell are common target of the cells of the immune system

the very high rate of sequence divergence is thought to reflect evolution by natural selection within the patient's body-

after 7 years the rate of sequence divergence declined significantly?????

How might natural selection account for the rapid rate of sequence evolution within a single patient, and what evidence exists to support the idea?

novel mutations that enabled virions to escape detection by the immune system increased in frequency as a result of selection

How might the high mutation rate of HIV complicate the design of effective anti-HIV drug therapies?

What is the CCR5 protein, and how is it related to the invasion of host cells by HIV?

DNA partly unwinds so that one of its 2 strands can serve as a template for RNA synthesis

As the RNA transcript is formed, it peels away, enabling the DNA to be rewound into a double helix

What is the CCR5-!32 allele, and what is its impact on HIV infection? What is the pattern of frequency distribution for the CCR5-!32 allele in human populations in Europe, Asia, and Africa?

What might account for the pattern of frequency distribution of CCR5-Δ32?

tautomers