BIO 2306 EXAM 4
describe how viruses are associated with cancer
- most cancer-causing viruses are retroviruses but some are also DNA viruses
tumor-suppressor genes
gene that normally inhibits cell division. recessive mutations in such genes often contribute to cancer.
evolution
genetic change that takes place in a group of organisms
explain the relationship between the amount of genetic drift and the effective population size
genetic drift is change in allelic frequencies due to chance. the amount of change in allelic frequencies due to genetic drift is inversely related to the effective population size (the equivalent number of breeding adults in a population).
gene library vs. cDNA library
genomic library: library of EVERYTHING cDNA library: only have EXPRESSED genes (look for mRNA)
list 2 things that characterize a gene pool
genotypic and allelic frequencies
phylogenetic tree
graphical representation of a phylogeny in the form of a branching diagram
orthologs
homologous genes found in different species that evolved from the same gene in a common ancestor
paralogs
homologous genes in the same species that arose through the duplication of a single ancestral gene
homology search and how this can be used to understand the function of a gene
homology search relies on comparisons of DNA and protein sequences from the same species and from different species. A homology search conducted on databases containing the DNA or protein sequences of other organisms may identify one or more orthologous sequences. If a function is known for a protein encoded by one of those sequences, that could provide information about the function of the newly discovered protein.
benign
if the tumor cells remain localized, the tumor is benign
gene cloning
the process in which a gene of interest is located and copied (cloned) out of DNA extracted from an organism. When DNA is extracted from an organism, all of its genes are extracted at one time. This DNA, which contains thousands of different genes.
metastasis
the movement of cells that separate from malignant tumors to other sites, where they establish secondary tumors
how are histone modifications maintained?
they are maintained across cell divisions
why are expression vectors needed?
they are special vectors that are required to express a foreign gene- and they need to have sequences that allow the gene to be transcribed and translated in addition to being replicated
nodes
point in a phylogenetic tree where branches split; represents a common ancestor
list some goals of the Human Genome Project
+ develop sequencing technology + sequence genomes of model organisms + determine the sequence of the human genome (3.2 billion bp) + identify all genes in human genome (˜20,000-25,000)
list some problems associated with sequencing of an entire genome
+ only small fragments (500-700bp) can be sequenced at a time + must fragment genome into millions of small overlapping fragments for sequencing + difficulty ordering the sequenced fragments
list 3 ways that DNA methylation represses transcription
- methylation inhibits binding of transcription factors - methylated cytosine attracts proteins that repress transcription - methylation attracts histone deacetylases
explain how mutant genes that promote vascularization and tumor spread can lead to cancer
- Angiogenesis is stimulated by growth factors and others proteins encoded by genes whose expression is carefully regulated in normal cells. In tumor cells, genes encoding these proteins are often overexpressed compared with normal cells, and inhibitors of angiogenesis-promoting factors may be inactivated or underexpressed. At least one inherited cancer—von Hippel-Lindau disease, in which people develop multiple types of tumors—is caused by the mutation of a gene that affects angiogenesis. - In the development of many cancers, the primary tumor gives rise to cells that spread to distant sites, producing secondary tumors. This process of metastasis, which is the cause of death in 90% of human cancer deaths, is influenced by cellular changes induced by somatic mutation. As discussed in the introduction to this chapter, the palladin gene, when mutated, contributes to the metastasis of pancreatic tumors.
describe 2 ways that a gene could be mutated for the purpose of reverse genetics
- CRISPR-Cas9 - knockout mice
explain how restriction enzymes can be used to create recombinant DNA
- DNA molecules cut with the same restriction enzyme have complementary sticky ends that pair if fragments are mixed together. - the nicks in the sugar-phosphate backbone of the two fragments can be sealed by DNA ligase
Replication by PCR requires:
- a DNA template (the fragment of interest, or target DNA) from which a new DNA strand can be copied - and a pair of single-stranded primers, each with a 3'OH group to which new nucleotides can be added
pyrosequencing
- based on DNA synthesis: nucleotides are added one at a time in the order specified by template DNA and the addition of a particular nucleotide is detected with a flash of light, which is generated as the nucleotide is added.
describe how inversions and translocations are associated with cancer
- both of these require breaks within the chromosome. cancer may result if the breakpoints lie within a tumor-suppressor gene, which would mutate the tumor-suppressor gene - both of these can rearrange the chromosome and may bring together sequences that stimulate cancer + for example: the rearrangement may place a cancer-causing gene under a different regulatory sequence that would up regulate its expression
know that many cancer cells have chromosomal mutations. explain if these mutations are a cause or effect of cancer
- cause: some cancers are associated with specific chromosome mutations - effect: most cancer cells have chromosomal mutations that result from the cancer
explain 3 effects of genetic drift
- change in allelic frequency within a population: Because genetic drift is random, the frequency of any allele is just as likely to increase as it is to decrease and will wander with the passage of time. the allelic frequencies in these populations change randomly from generation to generation. - loss of genetic variation: Through random change, an allele may eventually reach a frequency of either 1 or 0, at which point all individuals in the population are homozygous for one allele. When an allele has reached a frequency of 1, we say that it has reached fixation. Fixation, then, leads to a loss of genetic variation within a population. - different populations diverge genetically over time: because genetic drift is random, the frequencies in different populations do not change in the same way, and so populations gradually acquire genetic differences. Eventually, all the populations reach fixation; some become fixed for one allele, and others become fixed for the alternative allele.
understand the role of environmental factors in cancer
- chemical mutagens and radiation can mutate genes that predispose a cell to cancer - environmental factors can interact with genetic predispositions to cancer; ie some people carry a genetic variant of a gene that predisposes them to lung cancer, so smoking would further increase the chance for these people to develop lung cancer + environmental factors include tobacco use, diet, obesity, alcohol, and UV radiation & certain chemicals such as benzene (used in industrial solvent), benzo[a]pyrene (found in cigarette smoke), and polychlorinated biphenyls (used in industrial transformers and capacitors)
describe how reporter sequences can provide information about the location of gene expression
- close gene with its regulatory sequences - replace coding region with a reporter gene - insert into genome to create transgenic organism - observe location of the reporter
dominant/recessive behavior of oncogenes and tumor-suppressor genes
- defects in both copies of a tumor-suppressor gene are usually required to cause cancer. an organism can inherit one defective copy of a tumor-suppressor gene (heterozygous) and not have cancer because the remaining normal allele produced the tumor-suppressing product. - however, these heterozygotes are often predisposed to cancer bc the inactivation or loss of the one remaining normal allele is all that is required to completely eliminate the tumor-suppressor gene product. + sometimes, mutations in a tumor-suppressor gene can act in a dominant fashion; this may occur when the mutation alters the sequence or expression of the tumor-suppressor protein in such a way that it gains a new function that contributes to cancer.
list 3 types of chromosomal mutations that are associated with cancer
- deletion of tumor-suppressor gene - inversions - translocations
cancer cells
- do not respond to normal cell cycle controls - rob healthy tissues of nutrients
Explain in situ hybridization
- fix cell to slide - denature DNA/RNA - add probe that fluoresces
explain why cancer can be described as both a genetic disease and not a genetic disease
- genetic disease: cancer cells arise from defects of DNA - not a genetic disease: if cancer is inherited, every cell in body should have the cancer-causing gene and every cell should become cancerous; however, tumors typically appear only in certain tissues - not a genetic disease: many cancers do not run in families - not a genetic disease: huge environmental influence
describe how epigenetic changes are associated with cancer
- hypomethylation may activate oncogenes - hypermethylation may silence tumor-suppressor genes
what are the assumptions of the hardy-weinberg law?
- large population - random mating - not affected by mutation, migration, or natural selection + when the assumptions are met, reproduction alone does not alter allelic or genotypic frequencies and allelic frequencies determine frequencies of genotypes
there many different types of genes that contribute to cancer when mutated:
- oncogenes and tumor-suppressor genes - genes that control the cell cycle - DNA repair genes - telomerase - genes that promote vascularization and tumor spread - miRNAs
describe how CRISPR-Cas9 is used for genome editing
- scientists have engineered crRNA from bacteria with a sequence that is specific to the target sequence of interest - the other part of the crRNA contains a sequence that pairs with CAS9 protein = crRNA/Cas9 complex - this complex finds and binds to the target DNA sequence - Cas9 makes double-stranded cuts within the target DNA sequence - the cell's DNA repair mechanisms kick in to try to repair the cut-2 things can happen: 1. nonhomologous end joining is a repair pathway that repairs chromosome breaks but often causes inserts/deletions within the process-this would inactivate the gene 2. donor DNA can be inserted into the cell with ends complementary to the break sequence-homologous recombination would insert this sequence to repair the gene
dideoxy- sequencing method
- uses ddNTPs, which terminate DNA synthesis at specific bases - based on replication - the fragment to be sequenced is used as a template to make a series of new DNA molecules. in the process, replication is sometimes, but not always, terminated when a specific base is encountered, producing DNA strands of different lengths, each of which ends in a known base.
know the type of sequence that is analyzed in DNA fingerprinting
- uses micro satellites or short tandem repeats (STRs), which are very short DNA sequences repeated in tandem. these repeated sequences are found at many loci throughout the human genome - DNA fingerprinting can be used to identify people
understand how genes that control the cell cycle can play a role in cancer
-cyclins and CDKs are proteins that regulate checkpoints of the cell cycle; mutations in the genes that encode these proteins can cause the disruptions in normal cell cycle control, leading to cancer - external signals (hormones and growth factors) trigger a cascade of intracellular reactions that ultimately stimulate/inhibit cell cycle (signal transduction pathway); a mutation in genes that play a role in any of these reactions can lead to cancer
know how DNA fingerprinting works
1. DNA samples are collected and subjected to PCR 2. the length of the DNA fragment produced by PCR depends on the number of copies of the microsatellite sequence 3. the fragments are separated by gel electrophoresis. different sized- fragments appear as different bands.
understand how gel electrophoresis can be used to separate DNA fragments by size
1. DNA samples containing fragments of different sizes are placed in wells in an agarose gel. 2. an electrical current is passed through the gel. 3. all DNA fragments move toward the positive pole; small fragments migrate faster than large fragments. after electrophoresis, fragments of different sizes have migrated different distances. 4. a dye specific for nucleic acids is added to the gel 5. DNA fragments appear as bands on the gel.
explain how a gene library could be screened
1. a disc of nitrocellulose or other membrane is laid on top of the bacterial colonies 2. a few cells from each colony adhere to the nitrocellulose filter. 3. the cells are disrupted, and their DNA is denatured and fixed to the filter. 4. a labeled probe hybridizes with any complementary DNA 5. excess probe is washed off and the membrane is overlaid with X-ray film,... 6. ...which detects the presence of the probe 7. comparison of the membrane with the master plate reveals which bacterial colonies have the DNA of interest.
implications of the hardy-weinberg law
1. a population cannot evolve if it meets the hardy-weinberg assumptions, because evolution consists of change in the allelic frequencies of a population. (reproduction along will not bring about evolution) 2. when a population is in hardy-weinberg equilibrium, the genotypic frequencies are determined by the allelic frequencies from the genotypic frequencies, the reverse (determining the genotypic frequencies from the allelic frequencies) is possible only when the population is in hardy-weinberg equilibrium. 3. that a single generation of random mating produced the equilibrium frequencies of p2, 2pq, and q2.
list and describe the 3 causes of genetic drift
1. a population may be reduced in size for a number of generations because of limitations in space, food, or some other critical resource. genetic drift in a small population over multiple generations can significantly affect the composition of a population's gene pool 2. the founder effect- which results from the establishment of a population by a small number of individuals. Although the population may increase and become quite large, the genes carried by all its members are derived from the few genes originally present in the founders (assuming no migration or mutation). Chance events affecting which genes were present in the founders have an important influence on the makeup of the entire population. 3. genetic bottleneck - which develops when a population undergoes a drastic reduction in size.
list the 5 components of a PCR reaction
1. a solution that includes the target DNA 2. DNA polymerase 3. all 4 dNTPs (substrates for DNA polymerase) 4. primers 5. magnesium ions and other salts
explain the steps in a PCR cycle
1. a starting solution of DNA is heated to 90-100C to break the hydrogen bonds between the strands and thus produce the necessary single-stranded templates. the reaction mixture is held at this temp for only a minute or two. 2. the DNA solution is cooled quickly to 30-65C and held at this temperature for a minute or less. during this short interval, the DNA strands do not have a chance to reanneal, but the primers are able to attach to the template strands. 3. the solution is heated for a minute or less to 72C, the temp at which DNA polymerase can synthesize new DNA strands. - at the end of the cycle, two new double stranded DNA molecules are produced for each original molecule of DNA.
what are the predictions of the hardy-weinberg law?
1. allelic frequencies do not change 2. genotypic frequencies stabilize after one generation in proportions: p2 + 2pq + q2
the 3 elements of a cloning vector
1. an origin of replication, which ensures that the vector is replicated within the cell 2. selectable markers, which enable any cells containing the vector to be selected or identified 3. one or more unique restriction sites into which a DNA fragment can be inserted
describe the process of RNA sequencing
1. collect total RNA from cells 2. isolate mRNA 3. reverse transcribe into cDNA 4. fragment cDNA 5. sequence with next-gen sequencing 6. assemble sequences into RNA transcripts
explain the 2 steps involved in evolution
1. genetic variation arises 2. change in the frequencies of genetic variants
list 3 techniques that can be used to study the expression of a gene
1. microarrays 2. RNA sequencing 3. Reporter sequences
how a genomic library is created
1. multiple copies of genomic DNA are digested by a restriction enzyme for a limited time so that only some of the restriction sites in each molecule are cut. 2. different DNA molecules are cut in different places, providing a set of overlapping fragments 3. each fragment is then joined to a cloning vector... 4. and transferred to a bacterial cell,... 5. ...producing a set of clones containing overlapping genomic fragments, some of which may include segments of the gene of interest. CONCLUSION: some clones contain the entire gene of interest, others include part of the gene, and most contain none of the gene of interest.
list the 4 forces that change allelic frequencies
1. mutation 2. migration 3. genetic drift (random effects due to small population size) 4. natural selection
give the percent similarity between two humans
99.9% (more than 3 million base pairs will differ)
describe how transgenic animals could be used for the purpose of reverse genetics and how these animals are created
Another way in which gene function can be analyzed is by adding DNA sequences of interest to the genome of an organism that normally lacks such sequences and then observing the effect of the introduced sequences on the organism's phenotype. This method is a form of reverse genetics. An organism that has been permanently altered by the addition of a DNA sequence to its genome is said to be transgenic, and the foreign DNA that it carries is called a transgene. 1. mice are mated and fertilized eggs are removed from the female mouse. 2. foreign DNA is injected into one of the pronuclei 3. embryos are implanted in a pseudopregnant female. 4. offspring are tested for the presence of the introduced transgene 5. mice carrying the gene are bred to produce a strain of mice with the foreign gene
explain the statement "epigenetic changes are responsible for cell differentiation"
As a stem cell divides and gives rise to a more specialized type of cell, the gene-expression program of the cell becomes progressively fixed, so that each particular cell type expresses only those genes necessary to carry out the functions of that cell type. Though the control of these cell-specific expression programs is not well understood, changes in DNA methylation and chromatin structure clearly play important roles in silencing some genes and activating others.
ecological isolation
Reproductive isolation in which different species live in different habitats and interact with the environment in different ways, so that their members do not encounter one another and do not reproduce with one another.
describe how bioinformatics can be used to identify a gene
Bioinformatics develops and applies its analytical tools to "mine the data"; that is, to extract the useful information from sequencing projects. - after a genome has been sequenced, one of the first tasks is to identify potential genes within the sequence. + it develops databases of DNA, RNA, and protein sequences and tools for analyzing those sequences.
understand the relationship between mutant DNA repair pathways and mutant in proto-oncogenes/tumor-suppressor genes
Car has accelerator (proto-oncogene) and brake (tumor-suppressor gene). The car will be uncontrollable if the accelerator becomes hyperactive or if the brake does not work. A bad mechanic (defective DNA repair pathway) would not be able to fix the accelerator/brake
CpG islands and where they are located
CpG where p represents the phosphate group that connects the C and G nucleotides - are often located in or near the promoters of the genes - CpG islands are usually not methylated when genes are being actively transcribed, however, methylation of CpG islands near a gene leads to repression of transcription
describe how DNA methylation alters chromatin structure
DNA methylation refers to the addition of methyl groups to the nucleotide bases. in eukaryotes, the predominant type of DNA methylation is the methylation of cytosine to produce 5-methylcytosine. - often associated with repression of transcription
imprinted gene and how it gets imprinted all
Imprinted genes are genes whose expression is determined by the parent that contributed them. - Imprinted genes violate the usual rule of inheritance that both alleles in a heterozygote are equally expressed. + In genes that undergo genomic imprinting, the parent of origin is often marked, or "stamped," on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited from the mother and which was inherited from the father. The addition and removal of methyl groups can be used to control the activity of genes.
explain how we observe genetic variation today
In recent years, advances in molecular genetics have made it possible to investigate evolutionary change directly by analyzing protein and nucleic acid sequences. - Techniques such as protein electrophoresis, analysis of microsatellite variation, and DNA sequencing have revolutionized population and evolutionary genetic studies.
explain Knudsen's "two-hit hypothesis" as it applies to retinoblastoma
Knudson proposed that retinoblastoma results from two separate genetic defects, both of which are necessary for cancer to develop (Figure 23.3). He suggested that in the cases in which the disease affects just one eye, a single cell in one eye undergoes two successive mutations. Because the chance of these two mutations occurring in the same cell is remote, retinoblastoma is rare and typically develops in only one eye. Knudson proposed that children with bilateral retinoblastoma inherit one of the two mutations required for the cancer, and so every cell contains this initial mutation. In these cases, all that is required for cancer to develop is for one eye cell to undergo the second mutation. Because each eye possesses millions of cells, the probability that the second mutation will occur in at least one cell of each eye is high, so tumors may occur in both eyes at an early age. - called "two-hit" because in retinoblastoma only two mutations are necessary to cause a tumor
in situ hybridization
Method used to determine the chromosomal location of a gene or other specific DNA fragment or the tissue distribution of an mRNA by using a labeled probe that is complementary to the sequence of interest
explain how mutant miRNAs can lead to cancer
MicroRNAs (miRNAs) are a class of small RNA molecules that pair with complementary sequences on mRNA and degrade the mRNA or inhibit its translation. Given the fact that miRNAs are important in controlling gene expression and development, it is not surprising that they are also associated with tumor development. Many tumor cells exhibit widespread reduction in the expression of many miRNAs. - Lowered levels of miRNAs may contribute to cancer by allowing oncogenes that are normally controlled by the miRNAs to be expressed at high levels. - Research has shown that if, through genetic manipulation, the miRNAs are expressed at high levels, the development of tumors decreases. All of these findings suggest that altered expression of miRNAs plays an important role in cancer. In other cases, overexpression of miRNAs has been associated with cancer. For example, several miRNAs have been implicated in the process of metastasis.
explain natural selection and how this can chance allelic frequencies
Natural selection takes place when individuals with adaptive traits produce a greater number of offspring than do individuals not carrying such traits. If the adaptive traits have a genetic basis, they are inherited by the offspring and appear with greater frequency in the next generation.
hybrid breakdown
Reproductive isolating mechanism in which closely related species are capable of mating and producing viable and fertile F1 progeny, but genes do not flow between the two species because further crossing of the hybrids produces inviable or sterile offspring.
hybrid sterility
Reproductive isolating mechanism in which hybrid embryos complete development, but are sterile; exemplified by mating between donkeys and horses to produce a mule, a viable but usually sterile offspring.
hybrid inviability
Reproductive isolating mechanism in which mating between two organisms of different species takes place and hybrid offspring are produced, but are not viable.
behavioral isolation
Reproductive isolation due to differences in behavior that prevent interbreeding.
gametic isolation
Reproductive isolation due to the incompatibility of gametes. Mating between members of different species may take place, but the gametes do not form zygotes. Seen in many plants in which pollen from one species cannot fertilize the ovules of another species.
temporal isolation
Reproductive isolation in which the reproduction of different groups takes place at different times of the year, so that there is no gene flow between groups; exemplified by species of plants that flower at different times of the year and thus do not exchange genes.
mechanical isolation
Reproductive isolation resulting from anatomical differences that prevent successful copulation.
cohesive ends
Short, single-stranded overhanging end on a DNA molecule produced when the DNA is cut by certain restriction enzymes; also called a sticky end. Cohesive ends are complementary and can spontaneously pair to rejoin DNA fragments that have been cut with the same restriction enzyme.
explain the factors that influence the change in allelic frequency due to migration
The amount of change in allelic frequencies due to migration between populations depends on the difference between the populations in their allelic frequencies and on the extent of migration. - migration has 2 major effects: 1. it causes the gene pools of different populations to become more similar. 2. migration adds genetic variation to population. different alleles may arise in different populations owing to rare mutational events, and these alleles can be spread to new populations by migration, increasing the genetic variation within the recipient population. **over time, migration reduces the differences between populations
how a foreign DNA fragment can be inserted into a plasmid
The easiest method for inserting a DNA sequence into a plasmid vector is to cut the foreign DNA (containing the DNA fragment of interest) and the plasmid with the same restriction enzyme. - If the restriction enzyme makes staggered cuts in the DNA, complementary sticky ends are produced on the foreign DNA and the plasmid. - When DNA and plasmids are then mixed together, some of the foreign DNA fragments will pair with the cut ends of the plasmids. - DNA ligase is used to seal the nicks in the sugar-phosphate backbone, creating a recombinant plasmid that contains the foreign DNA fragment.
how to test for hardy-weinberg equilibrium in a population using a chi-square test
To determine whether a population's genotypes are in Hardy-Weinberg equilibrium, the genotypic frequencies expected under the Hardy-Weinberg law must be compared with the observed genotypic frequencies. To do so, we first calculate the allelic frequencies, then find the expected genotypic frequencies by using the square of the allelic frequencies, and finally, compare the observed and expected genotypic frequencies by using a chi-square goodness-of-fit test.
understand how mutation changes allelic frequencies
When the only evolutionary force acting on a population is mutation, allelic frequencies change over time because some alleles mutate into others. Eventually, these allelic frequencies reach equilibrium and are determined only by the forward and reverse mutation rates. The Hardy-Weinberg law tells us that when the allelic frequencies reach equilibrium, the genotypic frequencies will also remain the same. The mutation rates for most genes are low, so change in allelic frequencies due to mutation in one generation is very small, and long periods are required for a population to reach mutational equilibrium.
explain how SNPs can be used for genome-wide association studies
Within the past few years, SNPs have been used in genome-wide association studies to successfully locate genes that influence many additional traits, such as height, body mass index, the age of puberty and menopause in women, variation in facial features, skin pigmentation, eye color, glaucoma, and even susceptibility to infectious diseases such as meningococcal disease and tuberculosis. Unfortunately, the genes identified often explain only a modest proportion of the genetic influence on the trait.
branches
a connection between nodes in a phylogenetic tree representing an evolutionary connection between organisms
tumor
a distinct mass of abnormal cells due to cancer cells gradually losing their regular shape and boundaries
Mendelian population
a group of interbreeding, sexually reproducing individuals
reverse genetics
a molecular approach to the study of gene function that begins with a genotype (a DNA sequence) and proceeds to the phenotype by altering the sequence or by inhibiting its expression
single nucleotide polymorphisms
a single-base-pair difference in DNA sequence between individual members of a species
halotype
a specific set of linked genetic variants or alleles on a single chromosome or on part of a chromosome
cloning vector
a stable, replicating DNA molecule to which a foreign DNA fragment can be attached for transfer to a host cell
genome-wide association studies
a study that looks for nonrandom associations between the presence of a trait and alleles at many different loci scattered across a genome-that is, for associations between traits and particular suites of alleles in a population - use numerous SNPs scattered across the genome to find genes of interest
how to calculate genotypic frequency
add up the number of individuals possessing a genotype and divide by the total number of individuals in the sample (N). f(AA)= #AA individuals/N f(Aa)= #Aa individuals/N f(aa)= #aa individuals/N
annotation
after a gene has been identified, it must be annotated, which means linking its sequence information to other information about its function and expression, the protein it encodes, and similar genes in other species.
epigenome
all epigenetic modifications within the genome of an individual organism
cells 1. with no plasmid 2. with intact plasmid 3. with recombinant plasmid
amp resist B-gal color
metagenomics
an emerging field of genetics in which the genome sequences of a group of organisms inhabiting a common environment are sampled and determined. - metagenomics has been applied largely to microbial communities and has provided the ability to address to important issues: 1. the identification and study of microbes that cannot be cultured in the laboratory and 2. the study of the community structure of microorganisms. + so, metagenomic studies are a source of important new insights into microbial communities
reproductive isolating mechanism
any biological factor or mechanism that prevents gene exchange
functional genomics
area of genomics that studies the functions of the genetic information contained within genomes
structural genomics
area of genomics that studies the organization and sequence of information contained within genomes; sometimes used by protein chemists to refer to the determination of the three-dimensional structure of proteins.
explain the concept of clonal evolution of tumor cells
as cells acquire more mutations, they become the dominant cell type within the tumor - examples of these mutations: + DNA repair pathway + chromosome segregation (many cancer cells are aneuploids) + structural change that allows cell to invade other tissues - clonal evolution is the accumulation of mutations in a clone of cells. through clonal evolution, tumor cells acquire multiple mutations that allow them to become increasingly more aggressive and proliferate
genetic drift
change in allelic frequencies due to sampling error
plasmids
circular DNA molecules that exist naturally in bacteria - are commonly used as vectors for cloning DNA fragments in bacteria. - they contain origins of replication and are therefore able to replicate independently of the bacterial chromosome
expression vector
cloning vector containing DNA sequences such as a promoter, a ribosome-binding site, and transcription initiation and termination sites that allow DNA fragments inserted into the vector to be transcribed and translated
gene library
collection of bacterial colonies or phages containing DNA fragments that constitute the entire genome of an organism
cDNA library
collection of clones containing all the DNA fragments from one source - library consisting only of those DNA sequences that are transcribed into mRNA
comparative genomics
comparative studies of the genomes of different organisms
differentiate between dNTP and ddNTP
ddNTPs are identical with dNTPs, except that they lack a 3'-OH group
biological species concept
definition of a species as a group of organisms whose members are capable of interbreeding with one another but are reproductively isolated from the members of other species. because different species do not exchange genes, each species evolves independently. not all biologists adhere to this concept.
sampling error
deviations from expected ratios due to chance occurrences when the sample size is small
copy-number variations
difference among individual organisms in the number of copies of any large DNA sequence (larger than 1000 bp)
oncogenes
dominant-acting gene that stimulates cell division, leading to the formation of tumors and contributing to cancer; arises from a mutated copy of a normal cellular gene (proto-oncogene)
effective population size (Ne)
effective number of breeding adults in a population; influenced by the number of individuals contributing genes to the next generation, their sex ration, variation between individuals in reproductive success, fluctuations in population size, the age structure of the population, and whether mating is random
restriction enzymes
enzyme that recognizes particular base sequences in DNA and makes double-stranded cuts nearby; also called a restriction endonuclease
cladogenesis
evolution in which one lineage is split into two
anagenesis
evolutionary change within a single lineage
phylogeny
evolutionary relationships among a group of organisms or genes
explain how telomerase is related to cancer
inappropriate activation of the enzyme telomerase can contribute to the progression of cancer - telomeres: special sequences at the ends of eukaryotic chromosomes - in many tumor cells, sequences that regulate the expression of the telomerase gene are mutated, allowing the enzyme to be expressed, and the cell is capable of unlimited cell division. this mutation allows cancer cells to divide indefinitely. + (in most somatic cells, the ends of chromosomes cannot be replicated, and the telomeres become shorter with each cell division. This shortening eventually leads to the destruction of the chromosomes and cell death, so somatic cells are capable of only a limited number of cell divisions. In germ cells and stem cells, telomerase replicates the chromosome ends thereby maintaining the telomeres, but this enzyme is not normally expressed in somatic cells.)
what affect does inbreeding have on a population?
inbreeding can lead to inbreeding depression: decreased fitness arising from inbreeding; often due to the increased expression of lethal or deleterious recessive traits - bc the frequency of heterozygotes decreases and the frequency of homozygotes increases which means more of a chance for a recessive trait
bioinformatics
interdisciplinary field that combines molecular biology and computer science; develops databases and computational toots to store, retrieve, and analyze nucleic acid- and protein-sequence data.
what does the cell cycle need in order to function properly?
it needs stimulatory (proto-oncogenes) and inhibitory (tumor-suppressor genes) signals to function properly
probe
known sequence of DNA or RNA that is complementary to a sequence of interest and will pair with it; used to find specific DNA sequences
physical maps
map of physical distances between loci, genetic markers, or other chromosome segments; measured in base pairs - based on direct analysis of DNA - higher resolution - more accurate - restriction mapping - created for genomic analysis
genetic maps
map of the relative distances between genetic loci, markers, or other chromosome regions determined by rates of recombination; measured in recombination frequencies or map units - low resolution - limited detail - does not always accurately correspond to physical distances between genes - based on rates of crossing over
Hardy-Weinberg Law
mathematical model that evaluates the effects of reproduction on genotypic and allelic frequencies - applies only to a single locus
positive assortative mating
mating between like individuals that is more frequent than would be expected by chance. (ex: tall people mate preferentially with other tall people and short people with short people)
inbreeding
mating between related individuals that takes place more frequently than expected by chance
negative assortative mating
mating between unlike individuals that is more frequent than would be expected by chance (ex: tall and short people would preferential mate)
PCR
method of enzymatically amplifying DNA fragments (amplify DNA in a test tube outside of cells)
explain how histone modifications alter chromatin structure, specifically methylation and acetylation of histones
modification of histones include the addition of phosphates, methyl groups, acetyl groups, and ubiquitin. - many of these modifications take place in the positively charged tails of the histone proteins, which interact with the DNA and affect chromatin structure. + The addition of acetyl groups to amino acids in the histone tails (histone acetylation) generally destabilizes chromatin structure, causing it to assume a more open configuration, and is associated with increased transcription + The addition of methyl groups to histones (histone methylation) also alters chromatin structure, but the effect varies depending on the specific amino acid that is methylated; some types of histone methylation are associated with increased transcription and other types are associated with decreased transcription.
knockout mice
mouse in which a normal gene has been disabled ("knocked out")
migration (gene flow)
movement of genes from one population to another; also called gene flow
balancing selection
natural selection that maintains genetic variation - overdominance, in which the heterozygote has higher fitness than either homozygote, is one type of balancing selection
state how nonrandom mating affects the allelic frequency and the genotypic frequency
nonrandom mating alters the frequencies of genotypes but not the frequencies of alleles.
proto-oncogenes
normal cellular gene that controls cell division. when mutated, it may become an oncogene and contribute to cancer progression.
rooted
phylogenetic tree in which one node represents the common ancestor of all other organisms (nodes) on the tree. in a rooted tree, all the organisms depicted have a common ancestor.
gene tree
phylogenetic tree representing the evolutionary relationships among a set of genes
southern blotting
process by which DNA is transferred from a gel to a solid support such as nitrocellulose or nylon filter - one technique used to transfer the denatured (single-stranded) fragments from a gel to a permanent solid medium.
northern blotting
process by which RNA is transferred from a gel to a solid support such as nitrocellulose or nylon filter
speciation
process by which new species arise. (allopatric and sympatric)
western blotting
process by which protein is transferred from a gel to a solid support such as a nitrocellulose or nylon filter.
allelic frequencies
proportion of a particular allele within a population
genotypic frequency
proportion of a particular genotype within a population
neutral mutation hypothesis
proposal that much of the molecular variation seen in natural populations is adaptively natural and unaffected by natural selection; that is, that individuals with different molecular variants have equal fitnesses
epigenetics
refers to changes in gene expression or phenotype that are potentially heritable without alteration of the underlying DNA base sequence. - many epigenetic effects are caused by changes in gene expression that result from alternations in chromatin structure or other aspects of DNA structure such as DNA methylation
postzygotic reproductive isolating mechanisms
reproductive isolating mechanism that operates after gametes from two different species have fused to form a zygote, either because the resulting hybrids are inviable or sterile or because reproduction breaks down in subsequent generations - hybrid inviability - hybrid sterility - hybrid breakdown
prezygotic preproductive isolating mechanisms
reproductive isolating mechanism that prevents gametes from two different species from fusing and forming a hybrid zygote - ecological isolation - behavioral isolation - temporal isolation - mechanical isolation - gametic isolation
fitness
reproductive success of a genotype relative to that of other genotypes in a population
describe how retroviruses can cause cancer
retroviruses can cause cancer by: 1. mutating or rearranging proto-oncogenes or 2. inserting strong promoters new proto-oncogenes - retroviruses often contain strong promoters to ensure that their own genetic material is transcribed by the host cell. if the provirus inserts near a proto-oncogene, viral promoters can stimulate high levels of expression of the proto-oncogene, leading to cell proliferation.
next-generation sequencing technologies
sequencing methods, such as pyrosequencing, that are capable of simultaneously determining the sequences of many DNA fragments; these technologies are much faster and less expensive than the Sanger dideoxy sequencing method.
transcriptome
set of all RNA molecules transcribed from a genome
proteome
set of all proteins found in a cell (encoded by the genome)
recombinant DNA technology
set of molecular techniques for locating, isolating, altering, combining, and studying DNA segments; also commonly called genetic engineering
sympatric speciation
speciation arising in the absence of any geographic barrier to gene flow; in which reproductive isolating mechanisms evolve within a single interbreeding population
allopatric speciation
speciation that arises when a geographic barrier first splits a population into two groups and blocks the exchange of genes between them
genomics
study of the content, organization, and function of genetic information in whole genomes
gel electrophoresis
technique for separating charged molecules (such as proteins or nucleic acids) on the basis of molecular size or charge, or both
DNA fingerprinting
technique used to identify individuals by examining their DNA sequences
population genetics
the branch of genetics that studies the genetic makeup of groups of individuals and how a group's genetic composition changes over time
genomic imprinting
the expression of an allele depends on whether it is inherited from the male or the female parent - is caused by epigenetic differences in the alleles inherited from male and female parents. - the genetic conflict hypothesis suggests that imprinting evolves because of conflicting evolutionary pressures acting on maternal and paternal alleles
transformation
the mechanism by which bacterial cells take up DNA from the external environment - some types of cells undergo transformation naturally; others must be treated chemically or physically before they will undergo transformation - inside the cells, the plasmids replicate and multiply as the cells themselves multiply.
give an example of how RNA molecules alter chromatin structure with respect to X inactivation
they key player in X inactivation is a gene called Xist, which encodes a long noncoding RNA (IncRNA) - this RNA molecules does not encode a protein. instead, Xist IncRNA coats the X chromosome from which it was transcribed. it then attracts PRC2 and eventually PRC1 which produce epigenetic markers and other histone modifications that repress transcription.
how DNA methylation is stably maintained through DNA replication
through the process of cell division... 1. before replication, DNA is fully methylated at CpG dinucleotides 2. during replication, new DNA strands are synthesized without methyl groups 3. after replication, each new DNA molecule will have methylation on one strand but not the other: the DNA is hemimethylated 4. methyl groups attract methyltransferase enzymes, which add methyl groups to the unmethylated strand,... 5. ...resulting in fully methylated DNA
what is a way that many cancers arise?
through the sequential mutation of a number of genes (ex: colon cancer)
gene pool
total of all genes in a population
forward genetics
traditional approach to the study of gene function that begins with a mutant phenotype and proceeds to a gene that encodes the phenotype
malignant
tumor consisting of cells that are capable of invading other tissues
molecular clock
use of molecular differences to estimate the time of evolutionary divergence between organisms; assumes a roughly constant rate at which one neutral mutation replaces another
gene therapy
use of recombinant DNA to treat a disease or disorder by altering the genetic makeup of the patient's cells