genetics 6

Clonal Evolution

1.A single cell undergoes a mutation that causes the cell to divide abnormally 2.The cell proliferates giving rise to other cells with the same mutation 3.The cells often acquire additional mutations enhancing their proliferation rate 4.The tumor is eventually made up predominantly of cells carrying many mutations - Clonal evolution describes this process in which a tumor cell acquires mutations and proliferates more aggressively -When a cell divides the two are functionally clones of each other, the process of tumor development is referred to as clonal evolution. It begins when a single cell undergoes a mutation that causes the cell to divide abnormally. The cell proliferates giving rise to other cells with the same mutation. Cancer cells often acquire additional mutations enhancing their proliferation rate. The tumor is eventually made up predominantly of cells carrying many mutations. These cells won't respond to the normal cell cycle regulation mechanisms. -Clonal evolution describes this process in which a tumor cell acquires mutations and proliferates more aggressively

Evolution is a Two-Step Process

1.Genetic variation arises - Through mutation and/or recombination 2.If mutation/ recombination is passed on the frequencies of the genetic variants will increase or decrease when evolutionary forces are acting on the gene pool -There are shifts in allele frequencies within a gene pool - In the Fig. a mutation in the pigment gene arose in the gametic tissue of a black fish, the mutation causes its offspring to be a different color, this new color helps the fish blend into the muddy river bottom and avoid predation. Natural selection favors this allele so the frequencies of it increase over many generations

How Does Sampling Error Actually Arise in a Population? 3 mechanisms

1.Gradual reduction in population size over many generations due to environmental constraints that cause sampling error 2.Founder effect - establishment of a new population by a small number of individuals, often happens when an island is colonized by a small number of individuals 3.Bottleneck effect- drastic reduction in population size after a disease or environmental crisis - Northern elephant seals suffered a genetic bottleneck after humans almost hunted them to extinction. The population size has recovered, but their genetic variation is incredibly low because it was lost when the animals were killed. An important consideration in conservation biology. The number of animals present on earth at any given time is obviously important, but the preservation of genetic variation is also critical for the long term health of the species

Blue eyes are recessive to brown eyes in humans. If the frequency of blue-eyed individuals in a population is 16%, we can calculate that the frequency of the allele for blue eyes is:

40%

Using the data below, calculate the fitness of the Ee genotype. Genotype: ee EE Ee mean offspring produced: 25 15 13

0.5

Why is Cancer Considered a Genetic Disorder?

- Cancer is the result of defects in cell cycle regulation, which are ultimately caused by mutations to DNA sequences involved in cell cycle regulation •Ways in which mutations to cell cycle regulation can arise: -mutations to the genes can be inherited, some types of cancers run in families -chromosome abnormalities such as translocations, which can also be passed on -faulty DNA repair mechanisms can increase the chance the somatic mutation affecting the cell cycle will not be corrected, also inherited -certain viruses disrupt the cell cycle, not inherited, occurs through a person life time -direct damage to DNA from environmental agents, extremely common cause of cancer, not inherited - There are many, many, many genes involved in the cell cycle. Cancer is so common because mutations to any of these genes can lead to unregulated cell division. There is no one gene responsible for all cancers

Genome Evolution - Exons

- Comparison of whole-genome sequences has provided insight on the processes that affect the shape, size, complexity, and organization of genomes •Eukaryotic genes are often divided by introns -When exons are duplicated, genes can take on new functions (the immune system for example) •Exon shuffling: new genes evolve when exons are exchanged between different genes -Comparison of different genes has revealed that some are mosaics made up of exons from other genes

Cancer Cases in the UK Attributed to Environmental Factors

- 42.7% of cancer cases in the UK in 2010 were attributed to some form of environmental factor is a staggering statistic

What causes genomic instability?

- A mutation in a cell-cycle checkpoint gene that results in multiple chromosomal rearrangements and aneuploidy - A malfunction in the mitotic spindle checkpoint - A mutation in a DNA repair gene that results in a defect in the repair of chromosomal breaks

Changes in Chromosome Structure are Associated with Cancer

- Debate: are chromosomal changes the cause or result of cancer? •Chromosomal mutations appear to both cause and result from cancer -The nature of the relationship between chromatin structure and cancer have been up for much debate, are chromosomal changes the cause or result of cancer -Some cancers are consistently associated with very specific chromosome mutations, such as the translocation shown in the left figure -In other cancers the cause is known to be a single gene mutation, the chromosome abnormalities follow the development of cancer, this karyotype from a cancer cell shows numerous abnormal chromosomes that aren't present in healthy cells from the same induvial (right fig).

What is the frequency of cats with the bb genotype in the population?

- F(bb)= bb individuals/ N = 16/100= 0.16 or 16%, other 84% of the population are either BB or Bb, first would have to determine allelic frequency to determine frequency of BB and Bb

The Evolutionary Forces Interact to Increase and Decrease Genetic Variation

- Fig. illustrates how connected the evolutionary forces are and how the forces interact to cause increases and decreases in genetic variation within and between populations. For example. Mutation, migration, and Natural selection all work to increase genetic variation within populations

Effects of Migration

- Fig. shows a population of blue dots and red dots. Population 1 has a greater number of individuals with a blue allele, when they migrate to Population 2, the proportion of individuals in Population 2, carrying the blue allele increases . An equilibrium may be reached after many generations of migration

Phylogenetic Trees

- Graphical representations of the evolutionary connections between organisms or genes •A distantly related organism (outgroup) is often used to root the tree -The program constructing the tree needs to know what the ancestral state of each character is to end up with the most recently diverse species at the terminal nodes -In the tree Fig. the horse serves as an outgroup, they share a common ancestor with everything in the tree. The branches represent evolutionary connections between organisms. In certain types of trees the length of the branch is proportional to the amount of evolutionary convergence - terminal nodes represent the organisms for which the phylogeny is constructed - branches are the evolutionary connections between organisms. The length of a branch represents the amount of evolutionary divergence - internal nodes represent the common ancestors that existed before divergence - this phylogenetic tree is rooted, because this node represents a common ancestor of all other organisms in the tree

Homeobox Genes

- Homeoboxes have been found in all animals, as well as fungi and plants •Homeotic genes in animals contain subsets of nucleotides called homeoboxes that are similar in all homeotic genes - The Hox genes are homeotic genes, that have been found in most organisms and encode transcription factors that determine the identity of body regions along the anterior-posterior axis -Homeobox genes often exhibit the same correspondence between position on the chromosome and the region of the body they control. This is not a rule though, there are some organisms that do not display this pattern of arrangement -Similarities in sequence and order between mammals and drosophila, showing that the hox genes have been highly conserved through evolutionary time - genes shown in the same color are homologous - there are four clusters of Hox genes in mammals, each cluster containing 9 to 11 genes - the mammalian Hox genes are similar in sequence to the homeotic genes found in Drosophila, and they are in the same order today

Reproductive Isolation - Postzygotic

- If a hybrid zygote forms, postzygotic reproductive isolation mechanisms often prevent gene flow •Hybrid inviability: the hybrid zygote is not able to develop to adulthood (usually do not make it past embryonic stage) •Hybrid sterility: the hybrid survives, but can't reproduce, does not produce viable gametes •Hybrid breakdown: F1 hybrids survive and produce offspring, but the F2 offspring are inviable or sterile, loss of fertility after a generation

Loss of Heterozygosity

- If a person is heterozygous for a tumor-suppressor gene and the wild-type allele is mutated or lost, they may develop cancer, this is one of the reasons the BRCA1 test is done. If a person is heterozygous they are at a greater risk of developing cancer because it only requires one chromosome being mutated rather than two - A common way for the wildtype allele to be lost is through a chromosome deletion - Individuals who are heterozygous for a tumor-suppressor gene are predisposed to cancer, doesn't mean they will def develop cancer, but are more likely to than people with 2 wild type alleles

Reaching Mutational Equilibrium

- If the rate of forward and reverse mutations is equal, the frequencies will not change - mutational equilibrium - Forward mutations in the example increase the frequency of G2, but reverse mutations revert G2 back to G1 - Because mutation rates are usually very low, it takes many generations to reach equilibrium. Fig shows that despite a greater number of forward mutations, and lower number of reversions, mutational equilibrium will be reached after many generations 1. p decreases owing to forward mutation 2. p increases owing to reverse mutation 3. at equilibrium, forward mutation is balanced by reverse mutation

The General Selection Model

- If you have information about the initial allele frequencies in a population and the fitness values, you can calculate allelic frequencies after selection using the general selection model - The model can also be used to determine allele frequencies for specific types of selection - Don't need to remember the general selection models, just what they are used for

Haploinsuffiency

- In some tumor-suppressor genes, only having one functional copy can lead to cancer due to dosage effect - A heterozygote only produces half the amount of proteins as someone who is homozygous for the wild type allele - In some cases, the normal amount of protein is necessary for tumor suppression to occur - Haploinsuffiency is also involved in the development of cancer

You Can Use Data About a Homozygous Recessive Genotype to Determine the Allele Frequencies for a Population in Hardy-Weinberg Equilibrium

- p 2 + 2pq + q 2 = 1 - The goal is to determine the frequency of each allele: - B allele = p - b allele = q - p+q = 1 - BB = p 2 - Bb = 2pq - bb = q 2 -Assuming our cat population is not being effected by evolutionary forces, so we can use the Hardy-Weinberg equation to determine the allele frequencies using the recessive genotype -The reason we start with the recessive genotype in a study like this is because you can distinguish it phenotypically from the other phenotypes, we know the white cats only carry the bb alleles, there for, the frequency of the bb genotype is 0.16. -B=p=0.6 -B=q=0.4 - Now that we have the allele frequencies we can determine the genotypic frequencies - B allele = p = 0.6 - b allele = q = 0.4 - p+q = 1 - BB = p 2 = (0.6)sqr= 0.36 - Bb = 2pq= 2x0.6x0.4= 0.48 - bb = q 2= (0.4)sqr= 0.16 - Then plug in numbers to the formula, which reveals 36% of the population are heterozygous and 48% are homozygous dominant

Summary of Segmentation Genes

- Mutation in Gap gene: Example shows a mutation in the Kruppel gene which results in the complete deletion of all of the thorax segments and some of the adjacent abdominal segments - Mutation in Pair-rule genes: Example shows mutation in the even-skipped gene which causes a deletion in the even numbered segments -Mutations in Segmented-polarity genes: Example shows mutation in the gooseberry gene, which cause half if each segment to be replaced with a mirror image of half of the segment -Many of these mutations prevent an embryo from surviving to adulthood, but they can be observed during the earlier stages of development in fruit flies Deliberate mutations to many of these genes have helped researchers learn how different genes work together in specific points

Necrosis VS Apoptosis

- Necrosis differs from apoptosis in that it is an unplanned event and the cellular contents are dispersed rather than neatly reabsorbed - Necrosis is typically caused by disease or injury rather than natural cellular processes - Necrosis: 1. cell swells 2. cell lyses and releases cytoplasmic material - Apoptosis 1. DNA is degraded 2. Cell and nucleus shrink the nucleus fragments 3. shrinking continues and cell is engulfed by macrophage 4. macrophage phagocytizes apeptotic cell

Nonrandom Mating

- Nonrandom mating alters the genotypic frequencies in a population by affecting the way alleles combine •Positive assortative mating- the tendency for similar individuals to mate -Example: Orange cats preferentially mating with other orange cats •Negative assortative mating- the tendency for unlike individuals to mate -Example: Orange cats preferentially mating with tuxedo cats

The Level of Cyclin in the Cell Regulates CDK Activity

- Other checkpoints include G2/M and spindle-assembly-Cyclins don't do the phosphorylation, but they do activate the CDKs, which do carry out phosphorylation - CDK concentrations stay the same in the cell, but cyclin concentrations change and cause the CDKs to either be active or inactive - The cyclin level influence the G2/M and spindle fiber checkpoints as well -1. cyclin B accumulates throughout interphase. Near the end of G2 active MPF reaches a critical level, which causes the cell to progress through the G2/M checkpoint and into mitosis -2. Degradation of cyclin B near the end of mitosis causes the active MPF level to drop and the cell reenters interphase -3. increasing levels of cyclin B during interphase combine with CDK to produce increasing levels of inactive MPF -4. Near the end of interphase, activating factors remove phosphate groups from MPF, producing active MPF, which brings about the break downs of the nuclear envelope, chromosome condensation, spindle assembly and other events associated with mitosis -5. Near the end of metaphase, cyclin B degradation lowers the amount of active MPF, which brings about anaphase, telophase, cytokinesis, and eventually interphase

Development - Pattern Formation

- Pattern formation is a general term that describes the series of developmental processes that lead to the shape and structure of multicellular organisms •Patten formation in Drosophila melanogaster, fruit flies, has been studied extensively •Isolation of mutants has allowed geneticists to determine which genes are involved in development and what roles they serve

Genetic Drift

- Population size can cause deviations from the expected genetic composition •Genetic drift is essentially sampling error •Small populations only carry a sample of the genetic variation present in a large population •In small populations there are a limited number of gametes available to unite and produce progeny -Sample size is important to ensure that the variation within the larger population is represented -If the population is small enough it won't represent the full range of variation - Variance in allele frequency s2 is used to quantify genetic drift •The bw allele is responsible for eye color in fruit flies •Peter Buri randomly selected a small sample of fruit flies from each generation and allowed them to mate and give rise to a new generation •After ~20 generations the population became fixed for bw75 allele due to genetic drift - All of the flies had this one allele and the other allele was lost due to the effects of sample size. In each generation, the frequency the BW allele is lower and lower so each time you take a sample, the odds are less and less that you will select any individuals carrying it. Eventually all of the flies had the BW75 allele only

A single population becomes separated by a geographic barrier, and each population acquires genetic differences. Which of the following could happen if this barrier is removed and the two populations interact and attempt to mate?

- reproductive isolating mechanisms may not have evolved and thus the two species could successfully mate - prezygotic isolating mechanisms may have evolved, thus preventing the two populations from mating - postzygotic isolating mechanisms may have evolved thus preventing the two populations from producing viable or fertile offspring

Inbreeding Reduces Average Corn Yield

-Example shows when inbreeding on corn has a deleterious effect on corn yield -As the inbreeding coefficient increases, the average yield decreases, which is something farmers would want to monitor in their fields, ensuring that outcrossing is occurring helping to maintain higher corn yields

Inbreeding coefficient is a measure of the probability that two alleles are identical by descent

-If alleles are identical by descent, both copies are inherited from the same ancestor, though it could be removed a few generations -If something is identical by state, it's the same allele, but the two copies come from unrelated ancestors - these two copies of the A1 allele are descended from the same copy in a common ancestor; so they are identical by descent - these two copes of the A1 allele are the same in structure and function, but are descended from two different copies in ancestors; so they are identical in state

A geneticist has isolated a new mutation (m) in an egg-polarity gene of Drosophila. The m allele does not encode a functional protein. When two heterozygotes with this mutation (m/+) are crossed, it is expected that:

All of the offspring will develop into adults, but the m/m females will produce eggs that lack an mRNA needed for embryonic development - The mRNA is transcribed from the mother and she had a functional copy, so all offspring will develop into adults, but the eggs of m/m females will not be viable embryos after fertilization

Considering the clonal evolution of tumors, mutations in which kinds of genes would speed up the rate of accumulation of additional mutations?

DNA repair genes would speed up the rate of accumulation because the repair mechanisms are not working to correct the mutations

How do retroviruses contribute to the development of cancer cells?

If they insert themselves into regualtory genes and disrupt their function cancer can result

What problems does horizontal gene transfer cause for evolutionary biologists?

It can make reconstruction of phylogenetic trees difficult because it can obscure phylogenetic relationships.

Evolution within a single lineage is known as:

anagenesis.

How does apoptosis differ from necrosis?

apoptosis is often a natural stage in development while necrosis is not

Chromosomal changes:

can both cause and result from cancer

Blind eyeless cavefish differ from their sighted surface-dwelling relatives in that the blind fish have:

differing patterns of expression of genes that regulate development

Which of the following prezygotic reproductive isolating mechanisms best explains why salamanders that live in trees do not successfully mate with salamanders that live in soil by rivers?

ecological isolation

Homeotic genes:

encode transcription factors that regulate other genes

A fruit fly that develops without the head region probably has a mutation in which class of genes?

gap genes

What class of genes might you suspect to be mutated in a Drosophila mutant with antennae where its front legs should be?

homeotic genes

Which of the following is a form of postzygotic reproductive isolation?

hybrid sterility

Which of the following evolutionary forces would be expected to increase genetic divergence between two populations of a species?

mutation and genetic drift

The class of proteins known as cyclins:

oscillate in concentration during the cell cycle

Most forms of natural selection are directional in which one allele is favored over the other and is eventually fixed in the population. Which form of natural selection allows both alleles to be maintained?

overdominance or heterozygote advantage

The frequency of ss homozygotes is 0.09. Assuming the population is in H-W equilibrium, what is the frequency of Ss carriers in this population?

ss=0.9 , square root =0.3 =s 1-0.3=0.7=S Ss=2pq=2x0.3x0.7=0.42

Bicoid and nanos mutations exhibit genetic maternal effects in the offspring because

they are transcribed when the eggs form in the mother

Tumor cells are considered to be malignant if:

they invade other tissues.

Genomic and epigenomic differences are responsible for all ___________ in life

variation

A Tiny Bit of Flower Anatomy...

•A flower is essentially concentric rings of modified leaves called whorls -Whorl 1 - sepals -Whorl 2 - petals -Whorl 3 - stamens (pollen) -Whorl 4 - carpels (stigma & ovules) •Arabidopsis has 4 sepals, 4 petals, 6 stamens, and a stigma made of 2 fused carpels

Early Fruit Fly Development

•After fertilization, multiple nuclear divisions lead to a giant multinuclear cell •During an early stage in development the nuclei move to the edge of the cell forming the blastoderm -Some nuclei move to the pole and will become germ cells •The cell membranes grows inward around the nuclei creating a layer of cells surrounding the embryo 1.Sperm and egg nuclei fuse to create a single celled diploid zygote 2.Multiple nuclear divisions create a single multinucleate cell, the syncytium 3.The nuclei migrate to the periphery of the embryo and divide several more times, creating the syncytial blastoderm 4.The cell membrane grows around each nucleus, producing a layer of cells that surrounds the embryo. The resulting structure is the cellular blastoderm

Types of Evolution

•Anagenesis: changes that occur within a single lineage •Cladogensis: when one lineage splits into two and they no longer share a gene pool (speciation)

Cloning Experiments with Animals

•Animal cloning is more difficult, it is much easier to acquire and manipulate undifferentiated cells in plants, also raises fewer ethical concerns •Historical overview: - 1950s - nuclei from frog blastulas were injected into oocytes whose nuclei were removed resulting in adult frogs - 1960s - nuclei from differentiated cells were successfully used to produce adult frogs - 1997 - A sheep (Dolly) was cloned using the nucleus from the differentiated cell of an adult -2 broad categories of developmental research, (1) cloning organisms and (2) understanding how development actually occurs -Experiments involving cloning have helped us understand many aspects of development

Immunoglobulins AKA Antibodies

•Antibodies are the primary product of humoral immune response •Antibodies are made of 4 polypeptide chains that form a Y-shaped structure -Two heavy chains -Two light chains - They have binding sites for specific antigens -The heavy and light chain together form an antigen binding site that will recognize a specific molecule -The portion of the chain that binds to the antigen binding site is called the variable region and has a highly variable structure

Epigenetic Changes Are Associated with Cancer

•Cancer cells tend to have different patterns of methylation than normal cells •Overall, cancer cells tend to have lower levels of methylation indicating that genes that are not normally expressed, are being expressed •In some cancers, specific genes show higher levels of methylation indicating that genes that suppress division or trigger apoptosis may be turned off

Genome Evolution - Horizontal Gene Transfer

•Horizontal gene transfer - transfer of genetic material through non-reproductive mechanisms -Common in bacteria (conjugation, transformation, transduction) •Complicates phylogenetic analyses - genes that are present in an organism due to horizontal gene transfer do not reflect shared ancestry or decent from a common ancestor •A few cases of HGT in Eukaryotes -Certain aphids possess genes to produce carotenoids (normally acquired through diet) -These genes haven't been found in other animals, but the sequences are similar to those in fungi -Horizontal gene transfer is mostly linked with prokaryotes -Aphids and fungi obviously do not share a recent common ancestor, so the genes must have ended up in the aphid genome through some form of horizontal gene transfer

Sympatric Speciation

•How can gene flow be interrupted before an isolation mechanism exists? •Sympatric speciation occurs most frequently when a gene that affects resource utilization also affects mating preference 1.Individuals homozygous for one allele have high fitness on a specific resource and those homozygous for the other allele have higher fitness on a different resource (heterozygotes have lower fitness on both resources) 2.If the same gene is associated with mate preference reproductive isolation can occur while living in the habitat -Some scientists argue this is impossible, but we have examples of speciation that has occurred without a barrier -One example involves flies with a certain mutation that allows them to feed on different fruits. Mating takes place on the plants where they can feed, so they choose mates who can feed on the same fruit, which leads to speciation over time

How Do Mutations Interfere with the Cell Cycle?

•How do mutations in the G1/S checkpoint specifically lead to retinol blastomasa •If any component of the cell cycle is under- or overexpressed it can throw off the regulation •Retinoblastoma is caused by a mutation in the RB protein -If the RB protein is not present or functional, it won't bind to E2F and prevent the cell from entering S phase prematurely •Normally, if a cell is damaged or abnormal (a cancer cell) the process of apoptosis will be triggered -Mutations to certain genes prevent apoptosis which allows cancer cells to proliferate - The formation of cancer cells typically acquires damage to more than just one regulatory mechanism

DNA-Repair Genes

•In a healthy individual, DNA-repair mechanisms will often fix mutations that arise in the genes linked with cancer -If an individual has defects in genes from the DNA repair mechanisms there is a greater risk the mutations and key genes will go uncorrected resulting in cancer- Defects can increase the risk of developing cancer •Nonpolyposis colorectal cancer is inherited as an autosomal dominant disorder -A person who has one defective allele produces enough of the protein responsible for mismatch repair, but there is a high likelihood that a defect will arise in the normal allele in at least a few cells which can lead to tumors forming

Genes That Regulate Telomerase

•In normal adult cells, telomerase is not active -Finite number of times a cell can divide before the DNA degrades at the ends •Many tumor cells have mutations in the genes regulating telomerase -Telomerase is active allowing the cell to continue dividing infinitely. The fact that cancer cell lines are not subject to eventual death from telomere degradation is why they are often referred to as immortal cell lines -The relationship between telomerase activity and tumor progression is still being investigated - Polymerase activity in adults is often an indicator of cancer cells in the body

Inbreeding and Outcrossing Are Forms of Nonrandom Mating

•Inbreeding - preferential mating between related individuals -Positive assortment for relatedness -Affects all genes, not just a single trait -Leads to an increase in the proportion of homozygotes in a population •Outcrossing - avoidance of mating between related individuals •Inbreeding often has deleterious effects in species that are normally outcrossing -Because it causes a build-up of harmful recessive alleles in the gene pool - Inbreeding is linked to recessive disorders, which makes sense since it increases the proportion of homozygotes

Environmental Factors and Cancer

•Many things we encounter in daily life can cause somatic mutations and contribute to the formation of cancer •The most commonly studied factors include: -UV radiation -Tobacco and alcohol use -Diet -Industrial chemicals •Individuals who already have a genetic predisposition are at greater risk when exposed - This explains how two people could both get the same amount of UV exposure, but only one of them may end up developing skin cancer. The problem is that there is no comprehensive test to tell you what your risk factor actually is

Tumor suppressor genes

•Wildtype tumor-suppressor genes inhibit cancer by producing growth-limiting factors •Recessive-acting: both copies must be mutated to develop cancer -BRCA1 is a tumor-suppressor gene associated with breast and ovarian cancer, genetic tests are available to see whether a person carries mutant alleles for this gene - If you look at the Fig. you can see if a person who is homozygous for a mutation will not produce any of the inhibitory factors that help control cell division 1. Proto-oncogenes normally produce factors that stimulate cell division 2. Mutant alleles (oncogenes) tend to be dominant: one copy of the mutant allele is sufficient to induce excessive cell proliferation 3. Tumor-suppressor genes normally produce factors that inhibit cell division 4. Mutant alleles are recessive (both alleles must be mutated to produce excessive cell proliferation)

MicroRNAs and Cancer

•miRNAs are very important for regulating gene expression •Under and overexpression of specific miRNAs has been observed in many cancers •If the balance of miRNAs is off in the cell it can influence the expression of genes linked to cancer

Genes that control development in Drosophila act by regulating expression of other genes, EXCEPT in the case of:

Actually, all of these control expression of other genes.

How do cyclins and CDKs interact in controlling the cell cycle?

Cyclins, whose levels fluctuate during the cell cycle, activate CDKs by binding to them

What is Cancer

- cancer is not a single disease, it refers to a group of disorders characterized by the presence of cells that do not respond to the mechanisms controlling division - cancer cells divide rapidly and continuously, which is a problem because these cells create tumors that disrupt healthy tissues by crowding them and using up nutrients - the cells of advanced tumors can break off and start new tumors in other locations in the body

Migration can

- decrease genetic differences between two populations - increase the variation within a population that receives migrants

DNA Sequence Variation

- The discovery of techniques for isolating, amplifying, cutting, and sequencing DNA opened the door to studying genetic variation at the nucleotide level •Restriction site variation •Microsatellite variation •DNA sequence variation - All of these can be used to compare organisms at various taxonomic levels - Restriction site variation, Microsatellite variation, and DNA sequence variation are a few things that can be used to compare organisms at various taxonomic levels

Establishment of the Axes

- The egg-polarity genes are responsible for establishing the two main axes of development - These genes are transcribed into mRNA as the eggs form in the maternal parent and remain in the cytoplasm so they can be translated as soon as fertilization occurs - Egg polarity genes are an example of genetic maternal effect since the phenotype results from transcription of genes in the female parent, rather than the genotype of the embryo

What is a Species?

- A species is an evolutionarily independent group of organisms -Taxonomists give them unique names to ensure that scientists are referring to the same organism •How do we define them? -Biological species concept: a group of organisms whose members are capable of interbreeding, but are reproductively isolated from the members of other species - Phylogenetic species concept: a species is the smallest recognizable group of organisms that share a unique evolutionary history (determined through phylogenetic analysis) -Defining a species as an evolutionarily independent group of organisms can be challenging, defining a species is really an artificial practice, things are continuously speciating and evolving. In the case of prokaryotes horizontal gene transfer happens commonly. There isn't really a way to define them, but taxonomists give each group of organism unique names to ensure that scientists are referring to the same thing. Are need to place organisms in a hierarchy has led to different strategies for defining species into other taxonomic units. -The biological and phylogenetic species concept are two of the most popular ways to group organisms

Which of the following processes contribute to antibody diversity?

- Accelerated random mutation - Imprecise joining events of V, D, and J regions - Somatic recombination - Junctional diversity

Mutation

- All genetic variation ultimately arises through mutation •Mutation can change allelic frequencies in a population overtime, however the impact of mutation on Hardy-Weinberg equilibrium is usually negligible since they are rare occurrences •If mutation is the only evolutionary force acting on a population, allelic frequencies may change over time if one allele is susceptible to a mutation that converts it to another allele

Calculating Allelic Frequencies

- Allelic frequencies are calculated with data about the genotypes in a population - It is useful to describe the population in terms of alleles rather than genotypes since the alleles that will be passed on exist independently in the gametes of sexually reproducing organisms

Programmed Cell Death is Part of the Developmental Process

- Apoptosis - cells die and are degraded in a controlled manner •Some cells and tissues are not required in an adult organism and are removed through apoptosis during development -Tadpoles have tails, but adult frogs do not -Humans have webbing between fingers as embryos, but it is usually gone by birth •Apoptosis is highly regulated by multiple genes controlled by signals both inside and outside of the cell •Mutations to genes that either promote or repress apoptosis can lead to diseases

Flower Development in Arabidopsis

- Arabidopsis has been used extensively to study development in plants •The change from vegetative growth to flowering is an important developmental event in plants •Influenced by: -Season -Day length -Plant size -Nutrient availability -Many other factors

Clonal Evolution Summaryand Tumor Types

- Benign tumor: the tumor remains localized. They don't break off and travel elsewhere in the body - Malignant tumor: tumor cells break off and invade other tissues - Metastasis: the tumor cells induce secondary tumors as they spread - Fig. illustrates the process of clonal evolution. The cell first acquires a mutation effecting cell cycle regulation and begins to proliferate more than it should, later one of the daughter cells acquires another mutation causing further rapid division. This continues to occur, and as more and more mutations happen they begin to impact the phenotype of the cell, eventually the cell may become malignant 1.A cell Is predisposed to proliferate at an abnormally high rate. 2.A second mutation causes the cells to divide rapidly 3.After a third mutation, the cell undergoes structural changes A fourth mutation causes the cell to divide uncontrollably and invade other tissues

Biological Evolution

- Biological evolution refers to genetic changes in groups of organisms •Specifically, changes in allele frequencies in a gene pool (population) over time •Change of a single-celled zygote into an adult is not evolution (genes are not changing), we call this development instead •Individuals do not evolve - the gene pool does - Individuals can acquire a mutation that can be passed on, but evolution really refers to how it effects the gene pool

Population Genetics

- Branch of genetics that studies the genetic makeup of groups of individuals and how the genetic composition changes over time •Mendelian population: An interbreeding population with a set of genes (gene pool) •Populations evolve through changes in the gene pool •Population genetics is a form of evolutionary study

Key Events are Controlled by CDKs (cyclin-dependent kinases)

- CDKs are enzymes that add phosphate groups to other proteins, they play a role in other cellular processes besides the cell cycle as well •Some proteins are activated by phosphorylation while others are inactivated •CDKs are functional when associated with another protein called cyclin -The level of cyclin in the cell is what actually regulates CDK activity - Most processes that require phosphorylation of a protein rely on CDK's

Key Events are Controlled by CDKs (cyclin-dependent kinases)

- CDKs play a role in many other components of the cell cycle, but we will focus on the G1/S checkpoint

Inbreeding Depression Increases with the Intensity of the Inbreeding

- Inbreeding depression - increased appearance of lethal and deleterious traits - Self-fertilization (selfing) is the most intense form of inbreeding; reduces the proportion of heterozygotes by half in each generation - F = inbreeding coefficient -Selfing is very common in plants -On this graph F is the inbreeding coefficient. You can see that several generations of self fertilization results in an inbreeding coefficient of 1 indicating that the alleles are completely identical by descent. The population is also comprised entirely of homozygotes, if we look at the next two lines, you can see the inbreeding between siblings yields a much greater inbreeding coefficient than mating between first cousins. Humans are very susceptible to deleterious effects from inbreeding, and these effects are most apparent in cases where siblings have children together 1. selling reduces the proportion of heterozygotes by half in each generation... 2. ... leading to a completely homozygous population 3. Mating between siblings increases the percentage of homozygotes relative to random mating 4. mating between cousins also increases the percentage of homozygotes, but at a slower rate.

Egg-Polarity Genes

- Low nuclear concentrations of the Dorsal protein lead to the development of Dorsal structures. -Establishment of the dorsal-ventral axes- the concentration of the dorsal protein is what triggers the development of the dorsal-ventral axes. Low nuclear concentrations cause dorsal structures to form, while high nuclear concentrations cause ventral structures to form. A series of genes work together to regulate the concentration of the dorsal protein on each site of the embryo. Very important for axes to be established properly, so features such as wings and legs will develop on the correct side of the body. -The dark spots in the photograph show the high nuclear concentrations of the dorsal protein on the side of the embryo that will become ventral - Essentially: the two types of mRNA move to opposite ends of the cell leading to a build-up of each specific protein Establishment of the Anterior-posterior axes: You can think of this as head vs abdomen. 2 types of mRNA involved in this axes (the mRNAs are already present in the egg it is fertilized, after fertilization bicoid mRNA moves to the anterior (head) end of the embryo and bicoid proteins are translated leading to development of the anterior structures. In a similar manner the nanos mRNA migrates to the posterior end, where the germ-line cells are located. The proteins that are transcribed inhibit formation anterior structures to ensure the organism doesn't end up with two heads. 1.The bicoid mRNA is localized at the anterior end of the egg 2.Bicoid protein forms a gradient with high concentration at the anterior end, which induces development of the anterior structures of a fruit fly 3.The nanos mRNA is localized at the posterior end of the egg 4.After fertilization, the nanos mRNA is translated into Nanos protein, which becomes concentrated at the posterior end of the egg and inhibits formation of anterior structures

Changes in Gene Regulation

- Many evolutionary changes occur through changes in gene expression rather than changes to the genes •Example: Pigmentation in fruit flies Fruit flies living at higher elevations are darker in color No difference in the gene controlling pigment Reduced expression of the gene is responsible for color difference -Fruit flies living at higher elevation are darker in color, but an analysis of DNA sequences reveal that there are no differences in the gene controlling pigment in these two populations. Reduced expression of the gene is actually responsible for the color difference, this is important because it reflects evolutionary change, that would not be reflected in a molecular phylogeny -Studying evolutionary change in a comprehensive manner requires a synthesis of many fields and method. Molecular phylogenetics, chromosome analysis, epigenetics, and expression profiling are all useful for examining evolutionary histories

Gene Expression and Evolution

- Many major evolutionary adaptations are accomplished through changes in gene expression that influence development rather than direct changes to the structure of proteins. Explains how organisms with very similar genomes end up with vastly different phenotypes •Mexican tetras: Gene vs Gene expression -Cave dwelling tetras are blind and often eyeless -Surface dwelling tetras are the same species and have normal eyes and vision -Cave dwelling tetras still have the eye genes -A different pattern of gene expression during development causes the eyes not to form in cave dwelling tetras -Researchers have found that over and under expression in two key genes in the fish effects whether eyes will develop -Epigenetic changes are heritable, in this way they can be passed on in a population the same way mutation is. These cave fish are not mutants but their expression pattern is passed on. -The idea that evolution occurs both through changes in expression levels and changes to the DNA sequence directly has changed the way we think about species evolution and explains some areas of evolutionary theories that have been mysterious - Darwin's Finches: differential expression of the CaM gene leads to differences in beak shape and size. This allowed the birds to adapt to their habitat and food options much more rapidly than would have been possible if base sequence mutations were the only mechanism involved •Spineless Sticklebacks: deletion of an enhancer upstream from the Pitx1 gene prevents expression which stops the development of spines even though the genes for spine development are intact - This example shows that mutations to regions outside of the gene coding sequence can have major effects on the phenotype. In a way this is similar to the hemophilia example. Mutation causing the phenotype was not in the gene coding region, yet it still impacted the expression of the gene

The Hardy-Weinberg Law

- Mathematical model that evaluates the effects of reproduction on the genotypic and allelic frequencies of a population •The law assumes: - Large population size - Random mating - No new mutations - No migration - No natural selection - When the assumptions are met, reproduction alone will not affect genotypic and allelic frequencies generation to generation - The Hardy-Weinberg Law can be used to see if any evolutionary forces are acting on a population - The overall assumption of the Hardy-Weinberg Law is essentially no evolutionary forces are acting on the population •If all assumptions are met, random mating will produce proportions of p 2(AA), 2pq (Aa), and q 2 (aa) in the next generation - When the expected proportions match the observed frequencies the population is said to be in Hardy-Weinberg equilibrium - Indicates that no evolutionary forces are at work - p 2 + 2pq + q 2 = 1 - If he expected proportions do not match the observed frequencies, the specific differences can shed light on the types of evolutionary forces acting on the population

Migration

- Migration changes the allelic frequencies of a population as alleles are lost or gained •Gene flow is a descriptive term for migration •Migration can: 1.Prevent populations from becoming genetically distinct from one another (prevents speciation) This happens because migration increases the genetic variation in populations through the introduction of new alleles 2.Increase genetic variation in population (introduction of new alleles)

Reproductive Isolation - Prezygotic

- Prezygotic reproductive isolation mechanisms prevent gametes from fusing either by stopping organisms from mating or literally preventing fusion after mating •Ecological isolation individuals never meet because they use different parts of the habitat; think about birds, some remain high in the treetop, while others live close to the ground, they simply don't run into each other very often •Temporal isolation: reproduction occurs at different times, some flowers bloom in spring while others bloom in summer or late fall •Mechanical isolation: anatomical differences prevent mating; many insects have very specific reproductive structure and different species won't fit together so to speak •Behavioral isolation: differences in mating behavior prevent an organism from attracting a mate from another species; 2 different types of frogs in VA, one is a triploid and one is a diploid. They have two different mating calls, which ensures that they attract a mate who has the same chromosomes •Gametic isolation: mating may occur, but the gametes are incompatible and will not fuse; common mechanism for organisms that release their gametes into the wind and water (plants and fish), the odds are high that gametes from two different species will bump into each other, so it is important fusion doesn't occur - Reproductive isolation is a very broad term to describe many mechanisms that prevent organisms from reproducing

Protein Variation

- Proteins were the first type of molecular data used in population studies - Used before techniques for working with DNA were developed - If alleles for a given gene produce proteins of a different size, it can be revealed with electrophoresis (seen on a gel) - Does not reveal variation in amino acid sequence, synonymous mutations, or mutations in noncoding regions (set back of this technique) All of these things can be examined using DNA sequences

Oncogenes

- Proto-oncogenes are genes that carry out normal cellular function, but contribute to the development of cancer if they become mutated. Once mutated, they are refereed to as oncogenes •Dominant-acting: you only need one faulty copy for cancer to form •Some viruses can trigger proto-oncogenes to become oncogenes, in most cases this occurs when the proto-oncogene is incorporated into the viral genome and mutates into an oncogene, if that mutant copy is inserted back into the host cell, it can cause cancer to develop since oncogenes are dominant-acting •90% of cancers appear to originate from oncogenes -proto-oncogenes are not bad or harmful. We all have them, and they are an integral part of the cell cycle. A problem only occurs if they mutate. -Dominant acting disorders tend to have a broader impact on population, since only a single copy is needed 1. Proto-oncogenes normally produce factors that stimulate cell division 2. Mutant alleles (oncogenes) tend to be dominant: one copy of the mutant allele is sufficient to induce excessive cell proliferation 3. Tumor-suppressor genes normally produce factors that inhibit cell division 4. Mutant alleles are recessive (both alleles must be mutated to produce excessive cell proliferation)

- How can we produce such diverse antibodies from a limited number of genes

- Recombination creates different combinations and arrangements of immune response genes leading to diverse immune cells that attack specific antigens

Natural Selection

- Shifts in allelic frequencies from differential reproduction of certain genotypes •Individuals with advantageous genotypes produce more offspring •As long as the traits have a genetic basis they will show up with greater frequency in each generation •Natural selection promotes adaptation since genes that help an organism survive in certain environments will be passed on

Cell Cycle Regulation

- So, what actually controls all of these events??? -Most cells in an adult organism spend a majority of their time in the G0-nondividing phase. Your cells only divide when new cells are needed to replace old ones or repair an injury, they are not constantly dividing. The G1/s checkpoint is the first one a cell must pass in order to divide, once it does the DNA will be replicated and the cell will enter G2 to grow and prepare for mitosis. The G2/M checkpoint asses whether the cell is ready to divide and checks the integrity of the DNA that was replicated. After this checkpoint mitosis begins. A final checkpoint ensures that the spindle fibers are properly attached to the chromosome so that it will be properly segregated into the new cells. After cytokinesis, the newly divided cells grow and most likely go into the G0 phase. -What you should take note of is how many events that are occurring here. There is a lot of regulation required and many, many, genes involved in this over all process. A damaged gene at any point along the way can interfere with proper regulation. So what actually controls these events? That is a huge question

Why does protein variation, as revealed by electrophoresis, underestimate the amount of true genetic variation?

- Some amino acid changes may not affect electrophoretic mobility. - Some DNA sequence changes may not affect the amino acid sequence. - Dissimilar amino acid sequences may have identical electrophoretic migration.

How Do New Species Arise?

- Speciation: the process by which one population separates into two distinct evolutionary groups •Modes of Speciation -Allopatric: A population is separated by a geographic barrier preventing gene flow -Sympatric: Gene flow ceases due to factors other than geographic isolation (less common) •Mechanisms of speciation -Reproductive isolation -Polyploidy

Signal-Transduction Pathways

- The Ras signal-transduction pathway stimulates the cell cycle by conducting signals from external growth factors and hormones to the nucleus •When a growth factor binds to the receptor it triggers a conformation change that leads to Ras becoming active - binding of growth factor to the receptor causes a conformational change and the addition of phosphate groups - adapter molecules bind to the receptor and link to Ras. Ras binds to GTP and is activated •Ras activates the next protein in the pathway which in turn activates the next protein •Ultimately the cascade of activation leads to the activation of a protein that can enter the nucleus and activate the transcription factors necessary to transcribe key genes - Genes that encode proteins in this pathway often become oncogenes when this happens they can activate a transcription factor, when they shouldn't leading to replication - activated Ras activates Raf, which activates a protein called MEK, which activates MAP kinase - Activated MAP kinase moves into the nucleus and activates transcription factors

Signal-Transduction Pathways

- The decision to enter the cell cycle or stay in G0 is controlled by both internal and external signals •External signals are often initiated by hormones and growth factors - molecules that are too large to pass through the cell membrane •The signal transduction pathway is the mechanism that allows external signals to trigger a cascade of intracellular reactions leading to a specific response to the stimulus

Homeotic Genes

- The homeotic genes determine the identity of individual segments •Mutations to these genes result in body parts forming on the wrong segment - This fly has a mutation in the Antennapedia gene causing it to have legs where its antennae should be! -These genes lead to the result of final features such as eyes, antennae, wings ect. -These genes act once the segments have been established -Sometimes flies can survive to adulthood with these mutations depending on how severely it affects the flies ability to move around and feed. - The homeotic genes are activated by specific concentrations of the proteins produced by the segmentation genes - These genes encode transcription factors that regulate other genes - The homeotic genes in Drosophila are arranged in two complexes; the order on the chromosome corresponds to the order of expression along the anterior-posterior axis -We can see how development is a pathway, the products from the previous step of development regulate this stop -The antennae form on the head because a homeotic gene encodes a transcription factor which leads to the transcription of genes involved in antennae development in that body cycle. If the wrong homeotic gene is expressed in the body segment it can result in the wrong feature developing (ex. Leg being on head) -All the homeotic genes are found on chromosome 3 in drosophila

Inbreeding Results in the Loss of Heterozygosity

- The major outcome of inbreeding is the loss of heterozygosity, the proportion of homozygotes increase as the heterozygotes decrease over several generations. Here you can see that in the first generation ¼ is homozygous dominant for a trait, and ¼ is homozygous recessive, and ½ are heterozygous. After many generations of inbreeding genotypic frequency shift to the point that ½ are homozygous dominant an ½ are homozygous recessive, no heterozygous individuals

Extensions of the Hardy-Weinberg Law

- The model can still be used for more complex situations by using different formulas to calculate the genotypic frequencies -Loci with multiple alleles -X-linked loci

Examples of Tumor-Suppressor Genes

- The normal function of a tumor-suppressor gene plays a role in regulating aspects of the cell cycle that inhibit cancer formation - Table lists normal function of several tumor- suppressor genes and the type of cancer that results when they are non-functional. Just like with proto-oncogenes, these genes are all involved in the cell cycle

Oncogene Examples

- The normal function of proto-oncogenes is to stimulate the cell cycle, but oncogenes overstimulate the cell cycle resulting in cancer - Table provided examples of common oncogenes Many of the proto-oncogene normal functions include encoding transcription and growth factors that influence the cell cycle

Calculating Genotypic Frequencies

- The number of individuals possessing a specific genotype is divided by the total number of individuals in the study group - f () = frequency of the given genotype N = total number of individuals in the sample - f (BB) = BB individuals/N - f (Bb) = Bb individuals/N - f (bb) = bb individuals - Theoretical example of cat fur color: BB - black fur Bb - black fur bb - white fur

Segmentation Genes

- The segmentation genes affect the number and organization of body segments •Drosophila have about 25 segmentation genes •A mutation will typically disrupt an entire set of segments •These are transcribed after fertilization, so there is no genetic maternal effect, the embryos own genotype determines the proteins •Transcription is controlled by the Bicoid and Nanos protein gradience, development can be described as a pathway, since one step typically effects the following step. The embryos own segmentation genes encode the proteins needed for segments to be established, but the concentrations of the bicoid and nanos proteins involved in the anterior-posterior axes regulate transcription of the segmentation genes

Evolutionary Biology

- The study of genetics and evolution are closely linked since evolution occurs through genetic change within populations - "Nothing in biology makes sense except in the light of evolution"--Theodosius Dobzhansky, Pioneer of evolutionary genetics - Evolution is a foundational principle of biology, biology is the study of living systems so we must understand how living things have changed over time to understand why things function now - We can observe evolutionary change in populations in our lifetime as well as through examination of the fossil record (deep time)

Phylogenetic Trees Represent a Hypothesis

- There are many possible tree for a set of taxa; the goal is to find the one that is the most accurate representation of how the organisms are related using the available data - -There are different models and algorithms that computes use to do this, this table gives you an idea of how quickly the number of possible trees increases as the number of taxa in the data set increases. Generating a tree from 4 taxa is doable, but attempting to manually sort through all possible trees from 5 taxa will make you never take your computer for granted ever again. -Fig. shows the three possible configurations of a tree including 3 taxa, a chimpanzee, a human, and a gorilla

Organisms Exhibit Genetic Variation

- This underlying genetic variation is often observed phenotypically •Individuals may differ phenotypically, but still breed and produce fertile offspring, which makes them the same species under the biological species concept - Individuals appearing to have the same phenotype likely differ genotypically - Individuals with the same genotype still differ epigenetically -The lady bugs in his fig look different, but they are considered to be the same species because they can produce fertile offspring when they mate -We often see variation in populations, but even if we can't see it, members of the population differ on some level genetically

Evolutionary Histories

- We can examine the evolutionary relationships among organisms by studying the changes in homologous characters •Homologous characters have evolved from the same character in a common ancestor (inherited from a common ancestor) •Molecular and phenotypic data both provide useful homologous characters to analyze •Differences in homologous structures and DNA sequences are used to generate phylogenetic trees

Signal mutations can lead to cancer w transduction:

- a receptor becomes constitutively activated - ras becomes constitutively activated - a growth factor is constitutively expressed

Cancer is often regarded as a genetic disease because:

- agents that damage DNA, such as radiation, often lead to cancer. - some cancers run in families, suggesting heritability. - certain chromosomal translocations associate with specific cancers.

Cloning Experiments with Plants

-Plants have many regions of undifferentiated cells, they keep growing throughout life instead of stopping at a specific body plan like animals do -In one of the first cloning experiments, Frederick Steward cloned a carrot from a single phloem cell in the 1950s, which demonstrated that genetic information is not lost during determination, all cells still contain the information to become any type of cell, but something else directs the process rather than the DNA content itself -1. phloem tissue from the carrot is disrupted -2. and single cells are isolated -3. A single cells is placed in a nutritive medium that contains growth hormones -4. and eventually gives rise to a complete carrot plant

Fruit Fly Lifecyle

-The lifecycle and body plan of fruit flies makes an excellent model organism to study development. -In the first two steps the embryos experience rapid development, much of the initial development occurs in mere hours, which allows scientist to conduct many rounds of experiments in a short period of time. Fruit flies also have many body segments and their genes responsible for their development can be manipulated in various ways -1. a Drosophila egg develops into a hollow cylinder of cells -2. within a few hours segmentation appears -3. the embryo develops into a larvae that passes through 3 life stages... -4. ...before becoming a pupa. The pupa undergoes metamorphosis ... -5. ... and adult emerges -Adult fruit flies posses a head thorax and abdomen, they have 2 antennae, 2 wings, and 6 legs. It only take 9 days to go from a fertilized egg to an adult fruit fly.

What would you expect a flower to look like in a plant that ONLY has class A genes? (If I ask a question like this on the test I will provide the chart below - you just need to know how to interpret it)

A flower with only sepals

Which statement best describes the maximum parsimony approach to the reconstruction of phylogenetic trees?

A pathway is constructed that requires the minimum number of changes to arrive at the modern species from a common ancestor.

What is the biological species concept?

A species is a group of individuals that can interbreed but are reproductively isolated from members of other species.

Lesson 22

Cancer genetics

Lesson 21

Developmental genetics and immunogenetics

Lesson 24

Evolutionary Genetics -How speciation occurs and how we use phylogenies to examine the evolutionary history of life on earth

Which of the following statements best explains the process of allopatric speciation?

Genetic differences accumulate between populations that are isolated by a geographic barrier, eventually leading to reproductive isolation.

The ability to clone plants and animals from the nuclei of differentiated cells reveals that

Genetic information is not lost or mutated during the differentiation process.

Describe the effects of inbreeding on a population.

Inbreeding increases homozygosity and reduces heterozygosity in a population.

In normal somatic cells, chromosomes shorten each generation. In cancer cells you notice that the chromosomes are not shortening, even after many cell divisions. A mutation in the expression of which gene is the most probable cause of this observation?

Mutation in the expression of telomerase could result in the telomerase being continually expressed to prevent the shortening of chromosomes

What is the difference between an oncogene and a tumor-suppressor gene?

Oncogenes stimulate cell division and tumor-suppressor genes inhibit cell growth

How is the Ras protein activated and inactivated?

Ras is active when bound to a GTP and inactive when bound to a GDP.

Lesson 23

Population genetics - How the genetic composition populations change over time in response to the forces of evolution

What is the difference between prezygotic and postzygotic reproductive isolating mechanisms?

Prezygotic isolation prevents fusion of gametes; postzygotic isolation occurs after fertilization

What assumptions must be met for a population to be in Hardy-Weinberg equilibrium?

Random mating, large population, gene pool not affected by migration, selection, or mutation

What is the basic difference between allopatric and sympatric modes of speciation?

Sympatric speciation takes place between populations in the same geographic area.

What is the molecular clock?

The concept that the number of nucleotide base substitutions that have taken place between two organisms can be used to estimate the time since they shared a common ancestor

Briefly describe overdominance.

The heterozygote has greater fitness than either homozygote.

Which of the following is an assumption of the Hardy-Weinberg law?

The population mates randomly

Which of the following is true of tumor-suppressor genes?

The wild type allele produces growth-limiting factors

Which position of a codon evolves at the highest rate?

Third position since changes in the third position of a codon often specify the same amino acid

Not Everything Evolves at the Same Rate

•Comparison of molecular information has revealed that genes evolve at different rates -Different parts of the same gene often evolve at different rates! •Synonymous mutations do NOT affect the amino acid sequence -Often occur at the third codon position -Rate is higher in protein-encoding genes because they are not selected against, since the proteins function isn't compacted •Nonsynonymous mutations are nucleotide changes that alter the amino acid sequence -Rate varies widely among mammalian genes -Rate is lower since changes in amino acid sequence often have a detrimental effect -The rate at which a specific area of DNA changes is important when selecting a region to use for a phylogenetic study. If you are building a tree of closely related organisms, you want to use rapidly evolving regions, so there are differences the computer can use to construct the tree. If you are building a tree with distantly related organisms, you want to use more slowly evolving regions to make sure you are not building a tree filled with transversions -When working with genes that encode proteins, it is important to consider whether the mutations are synonymous or nonsynonymous -The main difference between synonymous codons occurs at the third position due to the wobble effect

Types of Natural Selection

•Directional selection - one allele or trait is favored over another -Leads to fixation of the favored allele and elimination of the other(s) over time •Overdominance (also called heterozygote advantage) - heterozygotes have higher fitness than homozygotes -Both alleles are maintained in the population even though one might be deleterious in homozygotes •underdominance - the heterozygote has lower fitness -Allele frequencies remain stable unless disturbed by another force - Sickle cell anemia in Africa is an example of heterozygote advantage in humans. Two copies of the mutant allele cause Sickle cell anemia which usually results in death before reproductive age, but people with one mutant allele have resistance to malaria, so the allele is maintained in populations of people who live in regions affected by Malaria

Darwin's Finches Are An Example of Allopatric Speciation

•Each island contained a population of birds and the conditions on the islands shaped the gene pools in different ways. We now know some of the phenotypic changes that occurred due to heritable changes in gene expression, epigenetics. This explains how such drastic changes occurred within the time frame •Limited gene flow occurred, but not enough to prevent speciation •Colonization of new islands after speciation has resulted in many islands with more than one resident species

Genetic Control of Flower Development

•Elliot Meyerowitz and his colleagues isolated homeotic mutations in Arabidopsis to learn about the developmental pathway •They placed the genes controlling flower development into 3 classes (A,B, and C) - Class A mutants only have carpels and stamens. Class B mutants only have sepals and carpels. Class C mutants only have petals and sepals. - Meyerowitz et al. hypothesized that each class was missing a different gene product or set of gene products necessary for proper development. It turned out that interactions between all three classes of genes produce functional flowers -When class A genes alone are transcribed, sepals form in the first whorl. When class A and B gene products interact, petals form in the second whorl. When class B and C gene products interact, they produce stamens in the third whorl. When class C gene products alone are produced, carpels form in the fourth whorl. -Class A mutants only have carpels and stamens because the Class A genes are necessary for sepals and petals to form -Class B mutants only have sepal and carpel because the Class B genes are necessary for petals and stamens to form -Class C mutants only have sepals and petals because class C genes are needed for stamens and carpels to form -What would happen if B and C genes were non functional? With only class A genes present, every whorl would contain sepals -If class C genes were the only ones present every whorl would contain carpels

Summary of Development in Drosophila

•Epigenetic changes are Crucial for Development -Early development is controlled by key genes activating or repressing the expression of other genes at specific times -Each type of cell expresses a specific set of proteins; the "program" is passed on when a differentiated cell divides -You start with a single celled embryo, which contains mRNAs for the egg polarity genes, which help determine the major body axes. Next the gap genes come into play and these lead to regional sections of the embryo being defined. Next the Pair-rule genes come into play, and individual segments are defined. After this the segment polarity gene leads to the polarity of individual segments being defined. Last, but not least the homeotic genes determine the identity of individual segments -Epigenetic change is the underlying mechanism responsible for the timing and differential expression of genes

Fitness and the Selection Coefficient

•Fitness is the relative reproductive success of a genotype -(W ) ranges from 0 to 1 -It is relative to the success of other genotypes in the population •The selection coefficient (s) is the relative intensity of selection against a genotype (1-W ) -When selection is for one genotype it is against the other - Example: - Genotypes: A1A1 A1A2 A2A2 - Mean offspring produced: 10, 5, 2 - Fitness (W ): Mean number of each genotype divided by the mean of the most prolific genotype (here it is A1A1) - Selection coefficient (1-W ): Subtract the fitness of each genotype from 1 - The most prolific genotype will always have a fitness of 1, most prolific will always have a selection coefficient of 0, which makes sense since there is no selection against this genotype

Development - Pattern Formation

•Further development of the early embryo includes: -Establishment of the anterior-posterior axis and dorsal-ventral axis -Determination of the number and orientation of body segments -Establishment of the identity of each individual body segment 1.The anterior-posterior and dorsal-ventral axes of the embryo are established 2.The number and orientation of the body segments are established 3.The identity of each individual segment is established

Allopatric Speciation

•Many ways to isolate species -Oceans -Mountains -Rivers - Whether or not gene flow occurs after secondary contact depends on the development of reproductive isolation mechanisms -Fig. illustrates how a geographic barrier such as a mountain range contributes to the isolation of a gene pool. At one end of the range we have a population in green, individuals from the starter population migrate to find new resources, the mountain range prevents them from coming into contact with each other, so gene flow stops. When gene flow stops the allele frequencies in the population begin to change due to the evolutionary forces at work. The same forces may not be present on both sides of the barrier, so the populations evolve in different ways. -Where things get interesting is when secondary contact occurs. This is when the two populations who have been evolving independently come into contact with each other again. -Whether or not gene flow occurs after secondary contact depends on the development of reproductive isolation mechanisms, if the isolation mechanisms have fully developed, the two populations will not breed and will be considered two different species under the biological species concept -Other types of barriers seen in allopatric speciation; oceans, rivers, mountains

Genotypic and Allelic Frequencies Are Used to Describe Gene Pools

•Mathematical models are often used to examine the genetic structure of populations •Describing the frequencies of genotypes and alleles in the gene pool is the first step in the process •A frequency is just a proportion; you may see them expressed as decimals or percentages •Frequencies are usually determined using a same population if the group of individuals being studied is large, since its not practical, or possible in some cases to collect DNA from every member of the population - As long as you have one piece of data from the population or sample, you can figure out the rest using mathematical models

Benefits of Molecular Data

•Molecular data directly represents evolutionary change •All organisms have DNA, so it can be used compare everything •Molecular data provides a large amount of variation to examine •Molecular data can be quantified •Molecular data can reveal information about the process of evolution •Molecular data can be easily stored and accessed in databases

Development Takes Place Through Cell Determination

•Multicellular organisms start as unicellular zygotes that undergo many cell divisions to ultimately produce adult organisms •The initial cells are totipotent and can give rise to any cell type •After certain patterns of expression have occurred, cells are committed to becoming a particular type of cell •This process is called determination

Factors Affecting Genotypic Frequencies in Populations

•Mutation •Nonrandom mating •Migration •Genetic drift •Natural selection - These are the primary forces of evolutionary change - If a population is in Hardy-Weinberg equilibrium, it is not being acted on by the forces of evolutionary change - Most populations are not in Hardy-Weinberg equilibrium, forces of evolution are acting to change the gene pool in some way

The Rate of Evolution Differs Within a Gene

•Mutation rates are often highest in parts of the gene that have the least effect on function -Third codon position -Flanking regions -Introns - Mutations in these areas can affect function in some cases, but typically they do not. You can see out of all regions shown for eukaryotic gene, the exons have the lowest number on nonsynonymous mutations per site per year

Mutations in Certain Types of Genes Are Associated with Cancer

•Over 350 different genes that contribute to cancer have been identified in humans so far and more discovered each year •Mutations in both types are associated with cancer •Cell cycle regulation genes fall into two types: 1.Genes that stimulate cell division -Oncogenes 2.Genes that inhibit cell division -Tumor-suppressor genes - •Mutations in both types are associated with cancer, but the mechanism is different for each

Darwin's Finches Are An Example of Allopatric Speciation

•Phylogenetic analysis revealed that the finches evolved from a single ancestral species that migrated to the archipelago - Members of the founding population gradually moved to other islands, but the distance prevented extensive gene flow, the ocean in between served as a geographic barrier facilitating allopatric speciation - Volcanic activity produces new islands, and these new islands were colonized - Charles Darwin was fascinated by the phenotypic variation observed in finished inhabiting the Galapagos islands, these finches have long served as a case study for the process of evolution, long before molecular phylogenetics it was suspected that the finches are a result of a migration event from south America to the islands. Phylogenetic analyses have revealed the finches evolved from a single ancestral species that migrated to the archipelago

Speciation Via Polyploidy

•Polyploidy allows the formation of fertile hybrids which are essentially new species since they can no longer produce fertile offspring with members of either original species •Very common in plants - Polyploidy: duplication of entire sets of chromosomes

Inbreeding Coefficient

•Ranges from 0-1 •A value of 0 indicates random mating •Values closer to 1 indicate that alleles are identical by descent (inbreeding) •The values are determined by examining pedigrees or studying the reduction in heterozygotes over several generations

Certain Viruses Are Associated with Cancer

•Retroviruses are capable of disrupting and rearranging host genes •Certain retroviruses have been shown to convert proto-oncogenes to oncogenes - Retroviruses can alter gene expression by inserting promoters into the host genome leading to unintended expression - Angiogenesis Contributes to Tumor Progression\•Like any other tissue, tumors must have a supply of oxygen and nutrients to survive •Angiogenesis, the growth of new blood vessels, is controlled by growth factors that are normally highly regulated -Genes encoding these factors are often highly expressed in tumor cells, contributing to their ability to survive in new locations by triggering new blood vessels to form - The development of aggressive tumors is a multistep process; regulation of numerous genes must fail for them to develop - Exposure to mutagenic and carcinogenic environmental agents greatly increases the odds of developing cancer, because it increases the number of genes with mutations. Past a certain point, the bodies natural repair mechanisms can't fix all the damage and the cells may not be eliminated through apoptosis

Alignment of Homologous Sequences

•Sequences are aligned to find positions where the organisms differ •Computer programs find the tree that most likely depicts the correct relationships between taxa •Principle of parsimony: the phylogeny that requires the fewest evolutionary events is considered to be the best hypothesis of the relationship between the taxa being studied - many types of trees are generated based on this logic. If you look at the fig. The nucleotide changes have been plotted on the tree, you can see the outgroup has a "t" at position 2 and everything else in the ingroup has a "c", the change from a "t" to a "c" unites the ingroup. If we look at the terminal nodes a change from a "t" to a "c" at position 8 is what distinguishes species A from species C. Species B also has the mutation from "t" to "c" at position 8, but when taking all positions into consideration, the placement of species B next to the outgroup results in the fewest evolutionary events in the tree. This is why computer programs are important for generating phylogenies. No way a human could run through all the possibilities from a molecular data set to find the most parsimonies' tree. This is only showing 1 nucleotide positions, full data sets include hundreds of thousands of characters. Scientists use different types of DNA for various studies. You can use noncoding DNA nuclear genes, organelle genes, or a combination of these depending on what you are trying to generate a tree for.

Inbreeding is a Normal Reproductive Strategy for Some Plants and Animals

•Some plants and animals inbreed frequently without harmful side effects -Many plants primarily reproduce through self-fertilization (easy to do since male and female parts are often on the same flower) - These populations eventually become homozygous, but the deleterious alleles are weeded out by natural selection resulting in homozygosity for beneficial alleles - Inbreeding is common in Arion circumscriptos, a highly successful slug species -Many plants reproduce through self fertilization which is easy to do since male and female parts are on the same flower -Evolutionary forces can interact, so you don't always have a simple outcome -Inbreeding is very common in some slugs these animals are very successful ecologically and have even become pests, so they are not suffering from their loss of heterozygosity

Cell Cycle Regulation

•The cell cycle is tightly regulated so that cells only divide when new cells are required •A mutation affecting one or more components of the regulation can cause the cells to divide inappropriately resulting in cancer •An overview of how the cell cycle is normally regulated will illustrate how many components are involved and why cancer is so common

Molecular Data Advanced the Study of Evolutionary Change

•The first method evolutionary biologists used to study evolutionary histories was examination of phenotypes •Extensive phenotypic variation exists within populations, but... -It is difficult to quantify -Less useful for studying distantly related organisms •Direct analysis of DNA offers more information - Fig. shows a single phenotypic trait in a population of butterflies. It takes a lot of skill and time to distinguish these butterflies, and it only gives you data on one trait

Antibody Diversity

•The immune system generates antibodies against antigens that are encountered during an individuals lifetime •Each person is capable of making 1015 different types of antibodies! •Since antibodies are proteins, the sequences to make 1015 different types are encoded in the genome •With only 1 x 105 genes in the human genome, how is this huge amount of diversity possible? This is what makes the structure of the immune system so fascinating - You were born with a rigid set of antibodies, you produce new ones during your life •Antibody genes are organized in segments allowing for recombination •Somatic hypermutation - the antibody genes are susceptible to deamination and it is often repaired by adding the wrong base leading to mutation. In this situation mutations are good because they increase variability. •Somatic recombination can create new arrangements of segments during a person lifetime •Junction diversity occurs because recombination of double strand breaks is often imprecise and bases are lost or gained- again mutation is a good thing •mRNA is processed to randomly remove duplicate segments, increasing the types of final products that can be made •Different light chains can combine with different heavy chains also increase the number of products you could end up with •Antibody genes are arranged in segments •Segments are duplicated many times with slight differences •Many different segments are randomly combined to produce the final antibodies during mRNA processing - Somatic recombination causes the arrangement of the segments to change again increasing the number of antibodies that can be generated 1. there are 30-35 different V gene segments... 2. ... 5 J gene segments 3. ... and C gene segment in germ-line DNA 4. In this example V2 is moved next to J3 through somatic recombination producing the DNA found in a mature B cell 5. The V-J-C pre-mRNA is processed so that the mature mRNA contains sequences for only one V,J, and C gene segment 6. This mRNA is translated into a functional light chain

Immunity Has Developed Through Genetic Recombination

•The immune system of vertebrates is crucial for protecting against infection from bacteria, viruses, fungi, and parasites •The immune system functions by recognizing specific molecules (antigens) and eliciting a response to their presence •The immune system must distinguish between the cell's own proteins and foreign particles so it doesn't destroy healthy tissue - Recombination creates different combinations and arrangements of immune response genes leading to diverse immune cells that attack specific antigens

Darwin's Finches Are An Example of Allopatric Speciation

•The molecular clock was used to estimate the time when each new species first appeared - The number of species present at a given point in time corresponds to the number of islands present at that same point in time -The nice thing about the Galapagos islands is that their age can be determined using isotope dating -Fig shows how many different discoveries have added to our understanding of one of the oldest case studies in evolutionary biology

Selection Against Rare Deleterious Recessive Alleles Is Inefficient

•The rate at which an allele is eliminated from a population depends on the starting frequency •When the frequency of a deleterious allele is high it will decrease at a rapid rate since it isn't passed on to any offspring if the individuals die before producing any; however, the frequency of the allele in heterozygotes increases since it isn't subject to the action of selection •Rare recessive alleles essentially "hide" from natural selection in heterozygotes •Whether or not homozygous recessive individuals pass on the allele has little impact on the frequency, since the allele is maintained in the heterozygotes - The eugenics movement was centered around the idea that you could rid the human gene pool of genetic diseases by preventing reproduction of those who have the conditions. The actions used to prevent people from reproducing were morally reprehensible and partially lead to the establishment of modern medicine and research of ethical standards. Aside from this the entire movement was fundamentally flawed since the alleles for these conditions would still be present in heterozygotes

The Molecular Clock

•The rate of mutation for each gene or region of a gene is consistent and can be used to estimate how long ago they diverged •Accuracy of the method, especially for examining short periods of time is still controversial -The molecular clock is typically calibrated will fossil evidence to yield the most accurate time frame. -Fig. plots the evolutionary history of life beginning with fish over millions of years based on changes in amino acid sequences

Mutations to Segmentation Genes

•There are three classes of segmentation genes based on what they control: -Gap genes define large sections of the embryo, such as the head, abdomen, and thorax -Pair-rule genes define regional sections and affect alternate segments -Segment-polarity genes affect the orientation of segments •Mutations in each class have different effects -Mutations of gap genes tend to causes deletions of adjacent segments -Mutations to Pair-rule genes tend to delete the same part of the pattern in every segment -Mutations to Segment-polarity genes affect polarity of the segment, part of the segment is replaced by a mirror image of part of another segment

Cancer Rates Are Higher in Certain Regions

•These trends are likely due to environmental and lifestyle choices associated with various regions •When people migrate to new areas they often experience similar cancer occurrence rates within a single generation, indicating environmental factors are to blame rather than genetic composition -Cancer rates differ regionally -Areas such as Hong Kong have high levels of air pollution, which could explain why throat and nose cancers are much higher in Hong Kong, than Utah. Looking for trends like this can help scientists find likely causal agents for specific cancers, and investigate ways to reduce exposure to these things

Changes in Chromosome Structure are Associated with Cancer

•Very advanced tumors contain many different types of chromosomal abnormalities leading some researchers to speculate that cancer is initiated after enough changes occur to destabilize the genome •Each new chromosomal mutation alters the expression of oncogenes and tumor-suppressor genes leading to the formation of advanced tumors - Genome instability tends to have a snowball effect, once one or two chromosome abnormalities arise, more occur as the cancer cell liner perliferate

Genome Evolution - Gene Duplication

•When an entire gene is duplicated, the extra copy is free from evolutionary constraints and can acquire mutations giving it new functions •Multigene families arise through this process - Fig. shows how the globin genes evolved through duplication and mutations that allow them to take on new functions

Regulation of the G1/S Checkpoint

•When the retinoblastoma (RB) protein is bound to E2F, the cell is prevented from entering S phase •Increasing levels of cyclin in the cell phosphorylate RB which activates it and triggers the release of E2F •E2F is a transcription factor that activates transcription of DNA replication genes allowing the cell to enter S phase - Fig. shows the specific series of events that control the G1/S checkpoint -RB binds E2F and keeps it inactive -Increasing concentrations of cyclin-D-CDK and cyclin-E-CDK phosphorylate RB... -... which activates RB and releases E2F -E2F binds to DNA and stimulates the transcription of genes required for DNA replication -This one component of cell cycle regulation involves interaction between cyclins, CDKs, the RB protein, the E2F protein, and the DNA sequence encoding the genes to carry out DNA replication. A mutation in any one of these can mess up the pathway and potentially allow the cell to enter phase when it shouldn't. -Sometime genes or proteins are given names related to how they were discovered rather than their function. The RB protein is a good example. Its normal function has nothing to do with Retinal Blastoma, but the mutant allele was discovered in a Retina Blastoma cell.

Genome Evolution - Whole-Genome Duplication

•Whole-genome duplication occurs through polyploidy and results in duplicate copies of every gene -Provides a lot of raw material for evolution to act on •Genome duplication is very common in plants •Evidence suggests that early vertebrates experienced several genome duplication events -Long considered controversial (first suggested in the 1970s), but genome sequencing data supports it - At some point in the distant past, early vertebrates were able to tolerate genome duplications that provided raw material for the evolution of multigene families, and new genes with new functions that were beneficial