Genetics Flashcards
(147 cards)
1
Q
Describe the cell cycle of Saccharomyces cerevisiae
A
- reproduces by budding
- grows
- nucleus separated between 2 cells
2
Q
what did mutagenesis of Saccharomyces cerevisiae reveal?
A
- mutants that stop at specific points during the cell cycle
- key genes required for the cell cycle
3
Q
what are temperature sensitive mutants?
A
mutants that do not progress through the cell cycle at the restrictive temperature
4
Q
describe the screening for temperature sensitive mutants
A
- indentify conditional mutants
- at permissive temperature the growth of all mutants is comparable to wild type
- temperature sensitive mutants have a wild type phenotype at permissive conditions
- mutant phenotypes are visible in the restrictive temperature
5
Q
what is special about mutations required for progression in the cell cycle?
A
causes the cells to arrest at the specific point in the cell cycle
6
Q
what is meant by restrictive?
A
see phenotype as cells arrest
7
Q
where would an S phase mutant arrest?
A
at the end of S phase
8
Q
in what way are non-cel cycle division mutants distinguishable from cell cycle mutants?
A
would arrest immediately irrespective of the phase of the cell cycle at restrictive temperature
9
Q
what is cdc2?
A
cyclin dependent on kinase - key regulator of the cell cycle
- mutant at 37degrees
10
Q
how was cdc2 identified?
A
use plasmid rescue to identify human cycle genes including cdc2
11
Q
describe how the plasmid was used to identify human cell cycle genes
A
- Grew at permissive temperatures
- Transform with human genes using mRNA
- Shift transformed cells to the restrictive temperature
- Only cells transformed with the wild type copy of the mutated gene will grew
12
Q
what are the different alleles of cdc2?
A
- One mutant = very slow to divide (recessive)
- Wee mutant = smaller size, divides quickly (dominant)
13
Q
how are cdc25 and wee1 similar to cdc mutants?
A
- similar phenotypes
- likely to act at the same point in the cell cycle
14
Q
what genes control entry into mitosis?
A
- cdc2
- cdc25 and wee1 proteins regulate cdc2
- longer pathway = more information can be fed in
15
Q
how do cdc25 and wee1 reulate cdc2 protein?
A
by a sequential series of phosphorylation events
16
Q
describe the development of flowers?
A
- concentric rings of 4 types of organs (whorls)
- initiate sequentially
- mutagenesis reveals genes involved
- 3 major classes of organ identitiy mutants: a, b, c
- each affect 2 whorls in the flower
- overlap generates distinct combinations
17
Q
Describe the ABC model
A
- a and c activatities must be mutually antagonistic
- ABC gene model predicts where ABC genes are expressed
18
Q
describe the floricaula mutant
A
- flowers replaced by shoots
- difference is one gene
19
Q
describe the flo gene in plants
A
- in young meristems
- expressed in the undifferentiated cells
- key role is switching on flowering
- if not switched on will differentiate into a shoot
20
Q
describe the eye mutation in drosophilia
A
wild type = red eyes
mutants = lacks pigment
could ask how many different genes are required for color
21
Q
what is a complentation test?
A
idenitfy which mutant have defects in the same gene
22
Q
how do you do a complentation test?
A
- cross mutants to wild type reveals that all the mutations are recessive to wild type
- complentation tests require recessive mutants
- when mutant is crossed to the same mutant the phenotype should be a mutant phenotype
23
Q
what does an allelic series represent?
A
different mutant alleles of the same gene
- each allele can have different amounts of gene activity which can lead to slightly different phenotypes
24
Q
what is an example of an allelic series?
A
Cystic Fibrosis = big genes - lots can go wrong
- lots of different alleles
- 50% of CF are homozygous for the same mutation
- 95% present a common phenotype
- some have other symptoms = difficult to diagnose
25
what is the allelic series in the C gene?
Wild type → C = fully functional enzyme and coat color
| Mutant c alleles produce partially functional enzymes → different coat colours and patterns
26
what 2 types of mutations can a modifier screen detect?
1. Enhancers 2. Suppressors
27
What are enhancers
enhance original mutant phentoype
28
what are suppressors?
suppress original mutant phenotype
29
how do caernorhabditis elegans show modifiers?
- have dumpy mutants in collagen
- can lead to death in embryonic or larcei stages
- find less or more extreme phenotypes
30
what is meant by aphenotypic?
when the modifier mutants have the same phenotype as the wild type
31
what happened when 3 strains of E.coli where sequenced and compared?
- shared shared genes ('core)
- genomes are dynamic in prokaryotes
- other genes were uniqeu or shared between pairs
32
what would there be unique genes between the 3 strains?
adaptation, different infections, generation phentoype of infection
33
what does comparative sequencing tell us?
about the complements of the genes
34
describe forward genetic analysis in E.coli
- make random mutations
- screen for interesting phenotypes
- map the mutation
- identify the gene that is disrupted
- study the function of the gene
35
what are the problems with forward genetic analysis in E.coli?
Forward genetic analysis doesn’t work that well
Genome is ~4300 with 3000 genes
Many mutants not accessible to forward genetics
36
what conclusion can be drawn about the undetected genes in E.coli?
2300 genes not detectable by their mutant phenotype and the function of these genes is unkown
37
what is the most probable explanantion for the udnetected genes in E.coli?
Phenotype of some mutants was not revealed or not detectable in the conditions of the screen or in environments that would reveal all possible phenotypes
38
how could we use reverse genetic analysis to identify genes in E.coli?
Sequence of the E.coli is genome - can predict where all the genes are located
Make a library of mutation in every single gene
Screen this library of mutants for phenotypes that have been gone undetected and identify a function
Plating robot
Can culture, grow, test in different conditions, confirms phenotypes to understand the function
39
what is the endosymbiotic theory?
```
Eukaryotic cell consumes a photosynthetic bacterium → incorporates it
Becomes an organelle
Cell wall broken down
Retains membrane
Transfer of genes to the nucleus
Retained through more eukaryotes
Can escape
```
40
how did comparative genetics provide proof for the endosymbiotic theory?
- plant cells contain at least three genomes (nuclear, mitochondrial and chloroplast)
- organelles have retained fragments of their original genomes
- rest has been transferred to the nucleus
41
how many genes does a plant have?
its own. mitochondria. chloroplast. also maybe viruses
42
what is chloroplast DNA most closely related to?
prokaryotic cyanobacteria DNA
43
what was the goal of sequencing the human genome?
Need to understand similarities and differences
Humans, fruit flies, yeast, mice
Establish functional categories for all human genes
Map and sequence model organisms
Develop new sequencing technologies
44
what happens when we compare genomes to other organisms?
find that no gene appears to be unique to humans
| - regulatory gene networks are controlled by the same families of transriptional regualtors in all eukaryotes
45
what could make humans different from other organisms?
- in some cases humans have more transcriptioal activators (can still be divided into the same groups)
46
what are transcriptional activators?
proteins that have a positive effect on the transcription of a subset of genes
47
what has comparative genomics shows between mice and human genomes?
- large segments are conserved
- Banding blocks are quite big showing high conservation
- Eg X chromosome is mainly the same colour
48
what is synteny?
conservation of gene order
49
what can synteny and comparative genetics be used for?
to locate human disease genes
50
what disease can also be found in drosphilia?
Prostate, colon, pancreatic cancers
Cardiovascular disease
Cystic fibrosis
Parkinson's and dementia
51
what is bloom's syndrome/werner's syndrome?
- growth disorder
| - characterised in yeast
52
what percent of the genes does the olfactory receptor gene family represent?
about 3% - huge
53
describe sense of smell
Receptors → proteins in olfactory system
906 gene sequences → code for receptors
Bind to 10,000 odour molecules
Specific cells → express only one receptor → odorant receptor → that cell connected to nervous system
54
how is there diversity in the human olfactory receptor genes?
lots of variation → alleles. ability to smell different scents
55
where else have olfactory receptor genes been found?
Have been found in yeast and other fungi
Size of gene families in in vertebrates are much bigger
80% of human olfactory genes appear in clusters
56
why do olfactory receptor genes appear in clusters?
Adjacent sequences → sequences duplicated
| Repeated elements → increased the chances of further duplication
57
what is gene duplication?
adjacent copies of a gene
58
what happens in gene duplication if there is selective pressure on both genes?
stay similar
59
what happens in gene duplication if there is selective pressure on one gene?
- one copy degrades
| - one copy acquires a new function
60
what is subfunctionalization?
duplicated genes perform different aspects of original function
61
what is neofunctionalization?
one acquires a new function (rare)
62
what are homologous genes?
all similar genes - common ancestor
63
what are orthologous genes?
homologous genes loacted in the genomes of different organisms (same function in different organisms)
64
what are paralogous genes?
two or more homologous genes located in the same gene
65
what are pseudogenes?
an inactivated and non-functional copy of a gene
66
describe the globin family?
- relatively small but equally ancient as the odorant
67
what are the different types of globins?
alpha globins, beta globins, nueron globins, cytoglobins, myoglobin
68
what is neuroglobin?
found in the brain, high affinity for oxygen, extra supplies of oxygen
69
what is cytoglobin?
relic of our aquatic ancestry, found throughout the body, deliver oxygen to tissues that are starved of oxygen
70
what is myoglobin?
release of oxygen into muscle eg running away from a predator, high affinity of oxygen
71
what do the clusters of alpha and beta globins suggest?
gene duplication
72
describe evolution of mammalian beta globin genes
Evolutionary outcome for the clusters are different in different species
Evolution in some gene families appears dynamic
In a relatively short space there have been different outcomes of the clusters
73
how do the globin cluster gene families compare to other similar families in mammals?
They both have pseudogenes
Expression of genes follows a developmental sequence
Means we have different subunits making hemoglobin in our bodies when were an embryo and adult → different affinities and requirements for oxygen
This only happens due to the gene cluster
Research → how this is regulated through developmental time → mechanism required to stagger expression → when to trigger the different genes
Mechanism exists because the gene cluster has evolved due to gene duplication events
74
how does gene duplication occur?
Gene duplication by unequal crossing over between homologous chromosomes
Recombination events between repeat sequences
Can occur between pair of homologous chromosomes or sister chromatids
Sometimes inherited, selected for in evolution
75
how does gene duplication allow a number of possibilites in evolutionary terms?
Once there is more than one copy of a gene - sequence changes can occur in the extra copies
Each structural domain within a protein is an individual unit in a polypeptide chain and is coded for in continuous series of nucleotides
76
what is domain duplication
Duplication of a segment of a gene
Addition genes can be created by domain duplication - duplication of segments within a gene
Has important implications for the functions of particular proteins
77
what is domain shuffling?
News genes can be creating by domain shuffling
| Potential to produce proteins with a brand new function
78
what is the evidence for domain shuffling?
Tissue Plasminogen Activator (TPA)
Important in wound healing → required for the breakdown of blood clots in vertebrates and stimulate cell proliferation
Artificial version is used in clinical medicine to treat strokes → tries to remove the damage a clot could do in a stroke
For TPA the domains have been shuffled to form an additional protein that's involved in the same process → that's been selected for as it helps wound healing in humans
79
what are the 3 domains in TPA?
```
finger module
growth factor domain
kringle structure
```
80
what is the finger module in TPA?
found in fibronectin - binds fibrin in clots to activate TPA
81
what is the growth factor domain in TPA?
found in epidermal growth factor, stimulates cell proliferation
82
what is the kringle structure in TPA?
found in plasminogen, binds to fibrin clots
83
what is whole genome duplication?
Generate extra copies of every gene (but no new genes)
84
what are the consequences of whole genome duplications?
This duplication increases the potential for new genes
The sequence of each duplicated gene can begin to change without modifying the function of the original gene because there is an additional copy of the original gene
frees up every sequence in the genome for evolution
85
in what organisms have many duplicated genes been found?
- S.cerevisiae → 800 gene pairs, 376 gene pairs occur in 55 duplicated sets
86
who does S.cerevisiae share a common ancestor with and how similar are they?
Kluyveromyces lactis shares a common ancestor with S. cerevisiae that lived 100 million years ago
K lactis and S. cerevisiae do not share the same gene pairs
This is because 10% of S. cerevisiae genes are likely to be derived from a whole genome duplication event
87
what is the consequence of a whole genome duplication event in S.cerevisiae?
difference in metabolism
In s.cerevisiae → as a by product of metabolising glucose it produces ethanol → it will eventually use that as a food source for when it runs out of glucose
In Kluvyrusj. Lactase → doesn't produce in ethanol, burns through the glucose much quicker, increases its biomass
extra copy of every single gene has increased the potential for the sequence of the extra genes to change without the function of the organism
88
how has alcohol dehydrogenase been affected by whole genome duplication events?
- it was copied through one
- Extra copies of the ADH gene allows new functions of the ADH enzyme to evolve
In S. cerevisiae ADH catalyses the conversion of acetaldehyde to ethanol
This enables S. cerevisiae to accumulate ethanol
This means S. cerevisiae can be used in fermentation and brewing
89
what makes us human?
Brain growth trajectory, brain size, descended larynx, eccrine sweat gland density, endurance running, earlier onset of labour and longer duration of labour, lacrimation (crying), T cell function (enhanced immune function), longer and more extended thumb
90
how are apes, neanderthals and denisovans similar?
human-lineage-specific genomic changes and correlate with phenotype
Hard to as there are parts of the human genome that are very hard to sequence
There are far more genomic differences between and other primate genomes than was originally though
First estimates indicated the sequences difference between chimpanzees and humans was 1.2%
The more complete analysis suggests as much as 5%
Often the hardest parts of the genome as were the differences are
91
what is a transposon?
a piece of DNA that can move from one location to another
92
describe the features of transposons
can be exploited to generate insertional mutants
Useful tools for mutagenesis
Transposon or transposable element is a discrete DNA sequence element that can move from one location in the genome to another
Often under the control of a transposase encoded by the element itself
93
how much of the DNA is transposons?
300,000 copies of DNA transposons
Evidence says that they don’t currently move → all appear to be inactive
But it represents a considerable amount of genes
44% of the human genome consisted of genome wide repeats
94
what is found at either end of a transposon?
a matching repeat at either end of the transposon → direct repeats allow transposons to be identified in genome sequencing projects
95
what are the 2 methods of transposon movement?
1. replicative transposition
| 2. conservative transposition
96
what is replicative transposition?
- move by replicating that sequence
| - transferred to a different location
97
what is conservative transposition?
where they hop from one place to another
98
what are retro elements?
transpose replicatively via an RNA intermediate
99
describe variegated pigmentation in maize
- caused by transposition in somatic cells
- mutations in pigment biosynthesis
- originally maize corn was dark pigmented
- yellow is a mutation
100
what does a full length Ac element contain?
a functional transposase gene
101
what does the Ds element contain?
has an internal deletion and does not code for a functional transposase
102
describe Ac - Ds transposons in maize
- The transposase recognises the 11 bp inverted repeats (IRs) at either end of the Ac and Ds transposers and catalyses the transposition of both Ac and Ds elements
- Maize has about 10 different types of Ds element of different sizes with internal deletions of 194 bp to several kb
- Recombination between pairs transposons can result in deletion of segments of the genome or chromosome breaks
103
what conclusions can be drawn about Ac - Ds in maize
- Recombination between transposons can also cause chromosomes to break and demonstrated that some regions are more likely to suffer chromosome breaks than others
- Mobile elements must be responsible for the break → these elements could move to a new position and the location of the chromosome break would move with them
- Ds were stable elements and did not move in the absence of Ac
- Ds could move in the presence of Ac
104
what does the size of the pigment sector depend on?
when the mutation occurred in development
| - frequency, size and shape
105
what happens to the pigment sector if the mutation happens early in devlelopment?
large sector
106
what happens to the pigment sector if the mutation happens late in devlelopment?
small sector
107
what happens if a transposon is jumping out of a gene?
restores the wild type function of that gene
108
describe what can be concluded by looking at phenotypes of an endosperm
- Flowering plant seeds are the result of a double fertilisation event - a diploid embryo and triploid endosperm
- In maize the colour of the kernel is determined by the triploid endosperm, not the diploid embryo
109
in McClintocks experiment what was C'?
prevents pigment being expressed in the aleurone layer, C (recessive) leads to pigment developing the aleurone layer
110
in mclintocks experiment what was Bz?
produces a purple pigment, bz (recessive) → produces a dark brown aleurone pigment
111
describe McClintocks experiment?
- selected male lines that were homozygous for dominant alleles and female lines that were homozygous recessive alleles
- looking for chromosome breaks
- Found bronze sectors but no purple ones → told her that the chromosome always borke between Bz and the centromere causing the bronze sectors
- The chromosome would always break in the same location
- The chromosome would always break in the same location → could confirm the presence of these breaks by comparing the sizes of the chromosomes
- Took her Ds line and crossed it with an Ac line → produced stable lines that didn’t produce any transposition events → could follow the chromosome breaks
- When she did this she only found purple sectors
112
why did McClintock choose male lines that were homozygous for dominant alleles and female lines that were homozygous recessive alleles?
alleles and female lines that were homozygous recessive alleles
Homozygous lines also meant that both alleles are passed onto the embryo and can be analysed in the future generations
McClintock would also know which alleles would be present in the triploid endosperm and in what proportion
113
what can happen when transposons move?
- they can induce chromosome breaks
| - chromosome breaks can generate new chromosome
114
what is the transposons role in genome evolution?
Transposons can initiate recombination events that lead to genomic rearrangements
Recombination between a pair of LINE-1 elements 35 MYa is thought to have generate the beta globin gene duplication resulting in Gy and Ay members of this family
Transposon directed gene expression → what happens if a transposon is inserted upstream
Gene identified in mouse which codes for a protein in the immune response → expression is regulated by sequence by transposable elements
115
what are HCNEs?
they are high conserved non-coding elements
116
what are the evolutionary origins of HCNEs?
traced back to the common ancestor of humans and fish
117
where are HCNEs found?
- regions where the frequency of genes is much lower and and emrbyonic development
118
how could transposons be drivers of evolutionary innovation?
Some conserved non-coding element families are derived from transposons
Transposons could have created lots of regulatory elements
119
what can transposons carry?
gene segments
120
what are MULEs?
mutator like transposable elements - often contain captured DNA sequences
121
where are Pack MULES found and what do they do?
Pack - MULEs transposons are widespread in rice
Pack - MULEs can collect different gene segments to make new hybrid genes and move these sequences to a new position
In between the inverted repeated regions are potential coding regions → there are exons and introns → captured by transposons and deposited in a different location
122
what proteins can pack MULES be translated in?
Putative peptide transporter
Mitogen activated protein
Kinase like protein
and others that we don't know
123
what were the type of genes that mendel studied?
- single gene traits
| - traits, for the most part, where not affect by the environment
124
what are complex traits?
- influence by multiple genes as well as by the environment
| - more prevalent than single gene traits
125
what are some examples of complex traits?
- height
- grain size
- human diseases (high blood pressure, obesity, diabetes)
- birth defects
126
how are the phenotypes of complex traits measured?
number, size, shape and yield
| - they are quantitative
127
what can effect the expression of complex traits?
- lifestyle choices
- inadequate nutrition → slow growth
- increased salt intake → high blood pressure
- diet high in fat/sugar → diabetes
- soil and moisture for crops
128
how do crops show variation?
from the environment
129
how do Mendel's laws apply to complex traits?
- Many genes contribute to complex traits, different genotypes have very similar phenotypes
- Difficult to see the effects of individual genes (mendelian ratios are not easily observed)
130
describe complex traits using 3 unliked genes with two alles (Aa, Bb, Cc) which influence the intesity of red coloration in seed casing of wheat
- even possible phenotypes ranging from nearly colourless to dark red
- two plants heterozygous for each of three unlinked genes affecting colour
- the genes act cumulatively to determine the intensity of red coloration
- phenotypes among the progeny appear as a normal distribution
131
what is the corn strain experiment with complex traits?
- Two strains of corn were grown in two different nitrogen environments
- Strain 1 = little variation in its yield in high or low nitrogen
- Strain 2 = a low yield in low nitrogen conditions and a much higher yield with more nitrone
- implies the effect of a genotype is sometimes specified by the environment, other times it is not
- implies there may be no genotype that is the ‘best’ across a broad range of environments and likewise no environment is ‘best’ for genotypes
132
what is phenotypic plasticity?
Phenotypic variation in different environment
| Complex trait heavily influenced by the environment → same genotypes producing a different phenotype
133
what is an example of phenotypic plasticity?
a butterfly that is orange in dry environments and blue in wet environments
134
what did Francis Galton find at height in populations?
When parents are below average height their offspring are taller than the parents but shorter than the population mean
When parents are above average height the offspring are shorter than the parents but taller than the average population
135
what conclusion did francis galton come to about height in populations?
- Height is a complex trait - the genotype is a large number of genes that contribute to height
- Contribution of the environment
- During meiotic cell division segregation and recombination break up combinations of genes that contribute to complex traits
136
what is heritability?
the proportion of the total variation due to genetic differences among individuals
137
what does heritability determine in a complex trait?
how closely the mean values of the progeny resembles that of the parents
138
use corn to explain heritability and complex traits
Genetically different strains of corn
- All of these cron plants are grown in the same environment → same greenhouse, same water, same soil
- Heritability of height of corn = 100%
Genetically identical strains of corn
- All of these corn plants are genetically identical
- Differences in height are due to environmental differences
139
why are twins good study when looking at heritability?
- separate the effects of genotype and environment in phenotype differences among individuals
- share the same genotypes → differences are due to their environment
140
what are the issues with studying twins?
the environment between twins is quite often identical itself
141
what is concordance?
defined as the percentage of cases in which both members of a pair of twins show the trait when it is known that at least one member shows it
142
what do high concordance rates suggest?
disorders have an important genetic component
143
what does it mean if none have a 100% concordance rate?
indicates that both genes and the environment play a role in the differences observed
144
how is cholestrol a complex trait?
- lots of genes affecting cholestrol
- environment has a big impact
- Genetic interactions between genes for one type of cholesterol and genes for another type of cholesterol
- Many of the genes affect two or even three types of molecules associated with cholesterol
- Many of the genes interact with one another and it is difficult to interpret the relationship between these genes and cardiovascular disease
145
if you have a few traits for complex trait what effect will this have?
a few traits will have a relatively large affect
146
give some examples as to why using personalised medicine would be more effective.
- Asthma → differences in response to inhalers and have been traced to genetic variation in the gene ADRB2
- Alzheimer’s disease → some treatment drugs are less effective in women with a particular genotype for APOE gene
- High cholesterol → drug treatment can cause muscle weakness: more than half of the cases of muscle weakness can be traced to genetic variation
147
Why might reciprocal crosses be carried out with only male flies scored?
To test for sex linkage
| This would be revealed in the male
