Lec 02- DNA Chromosomes and Genomes 2 Flashcards
1
Q
What is epigenetics?
A
a form of inheritance that is superimposed on the genetic inheritance based on DNA
2
Q
What are 3 examples of epigenetics?
A
- DNA methylation
- Chromatin structure
- Histone modification
3
Q
What are the 3 challenges to the idea that histones are thought to just be involved in packaging of DNA?
A
- Mammalian chromatin contains equal mass of histones and non-histone proteins
- Histones are highly conserved
- Heterochromatin silences the genes it packages without regard to sequence and is directly inherited by daughter cells
4
Q
What does heterochromatin do?
A
- silences the genes it packages without regard to sequence
- is directly inherited by daughter cells
5
Q
What suggests that histones have other functions besides purely structural?
A
other proteins bind to histones
6
Q
How many amino acid differences are there between mammals and peas?
A
only 2 amino acid differences on H4
any change = deleterious
7
Q
Heterochromatin characteristics
A
- chromatin that is very condensed
- stains darkly throughout the cell cycle (even in interphase)
- late replicating
- genetically inactive
- very few genes
8
Q
The genes that are present on heterochromatin are resistant to ________
A
gene expression
9
Q
Where is heterochromatin highly concentrated?
A
at centromeres and telomeres
10
Q
What is position effect?
A
activity of a gene depends on position on the chromosome
11
Q
What happens if a gene’s position is relocated near heterochromatin?
A
- it will be silenced
- zone of inactivation spreads a different distance in different cells
12
Q
What is euchromatin?
A
all the rest of chromatin that is less condensed than heterochromatin
13
Q
What kind of modifications are the amino acid side chains of histones subject to?
A
covalent modifications
14
Q
Where do covalent modifications of histones occur?
A
histone core and tail
15
Q
Acetylation of lysine characteristics
A
- loosens chromatin structure
- added by histone acetyl transferases (HATs)
- removed by histone deacetylase complexes (HDACs)
16
Q
Characteristics of Mono, Di, and Tri-methylation of lysines
A
- Added by methyl transferases
- Removed by histone demethylases
17
Q
What covalent modifications occur with histones?
A
- Acetylation of lysine
- Mono, di-, tri-methylation of lysine
- Phosphorylation of serine
18
Q
What does the recruitment of the histone covalent modification enzymes depend on?
A
gene regulatory proteins
19
Q
Are histone modifications reversible?
A
yes, but can persist long after regulatory proteins have disappeared
20
Q
What determines how/when/if gene expression takes place?
A
the types of proteins the modified DNA attracts
21
Q
Varient histone proteins exist for each core histone except which?
A
H4
22
Q
Varient histone proteins are present in ___________ amounts than core histones and are __________.
A
much smaller amounts
less well-conserved
23
Q
When are major histones synthesized?
A
during S-phase
24
Q
What are major histones assembled into?
A
nucleosomes on daughter DNA helices just behind the replication fork
25
When are variant histones synthesized?
during interphase
26
What are variant histones inserted into?
already-formed chromatin
27
What do varient histones require?
histone exchange process catalyzed by chromatin remodeling complex
28
Histone code characteristics
- has specific meaning for cell
| - determines how/when DNA is packaged in nucleosome
29
How is the histone code read?
by the code reader complex
30
What does the code reader complex involve?
joint recognition of histone tail and covalent modifications
31
Histone code can ________ as the cell needs change
change
32
What happens after modifying enzyme marks one or few neighboring nucleosomes?
chain reaction can ensue
33
What enzymes spread the mark over the chromosome?
the code reader-writer enzyme
34
What do the code reader-writer complexes also contain?
an ATP-dependent chromatin remodeling protein
35
All the chromatin remodeling complexes work together to _________
either condense or decondense long stretches of chromatin as the reader moves along
36
What 2 mechanisms halt the spread of chromatin modifications?
- physical barriers
| - enzymatic barriers
37
What does the HS4 region on the chromatin do?
-protects the b-globin locus from silencing
38
What cluster does the HS4 rein on chromatin contain?
cluster of histone acetylase binding sites
39
What does the centromeric heterochromtin contain which makes it special?
- centromere-specific H3 histone
- CENP-A
- other proteins that pack the nucleosomes into dense arrangements to form kinectochore
40
What kind of structure is required for attachment of the mitotic spindle to the heterochromatin?
dense arrangements of nucelosomes
41
What kind of DNA sequences do centromere sequences in humans consist of?
alpha satellite DNA
42
What is alpha satellite DNA?
short repetitive DNA sequences
43
Centromeric heterochromatin is defined by assembly of proteins, not ____________
DNA sequence
44
Where are alpha satellites found?
at non-centromeric positions in the genome
45
Where can new centromeres (neocentromeres) form?
spontaneously on fragmented chromosomes
-some of which lack alpha satellite DNA
46
How is centromeric chromatin organized?
- 2 alternating types of chromatin
| - CENP-A binds the kinectochore
47
What are the 2 alternating types of chromatin?
- nucleosomes with CENP-A (centromere-specific histone H3) on outside fold
- nucleosomes with normal H3 that is dimethylated at lysine 4 on inside fold
48
What does de novo centromere formation require?
requires a "seeding" event on alpha satellite DNA
49
What are directly inherited by the daughter strands at the replication fork?
H3-H4 tetramers
50
What happens once the de novo centromere is formed?
it is directly inherited in each round of replication
51
What are the largest known chromosomes?
lampbrush chromosomes from amphibian oocytes
52
How are the lampbrush chromosomes from amphibian oocytes structured?
series of large chromatin loops emanating from a linear chromosome axis
53
Each chromosome occupies _________
its own area in the nucelus
54
With what does heterochromatin preferentially associate?
the nuclear lamina
55
Where are gene-rich regions dispersed?
throughout the chromosome
56
Chromatin structure and location changes during ______________
gene expression
57
When do you see "chromosome puffs"?
during decondensation of chromatin during gene transcription
58
Where do actively transcribed genes extend?
extend out of its area on an extended chromosome loop
59
How are different activities localized in the nucleus?
- nucleus interior = very heterogeneous
- different neighborhoods have effects on gene expression
- biochemical environments have high local concentrations of enzymes and molecules for specific processes
60
What are 2 processes that distinct biochemical environments have high local concentrations and enzymes for?
- DNA repair "foci"
| - RNA synthesis
61
Characteristics of mitotic chromosomes
- highly condensed
| - final level in chromosome packaging
62
Two daughter DNA molecules replicated in interphase are separately folded to produce ____________
2 sister chromatids
63
What holds chromatids together
their centromeres
64
What is the purpose of condensation?
- Disengagement of sister chromatids to allow separation for cell division
- Protection of fragile DNA molecule as separation occurs
65
What proteins aid compaction?
condensins
66
What are condensins?
- use ATP hydrolysis
- coil DNA molecules into chromatids
- major structural component of the core of every Metaphase chromosome
67
Cells that do not have condenses have ______________
abnormal condensation
68
What are homologues?
- genes that are similar in both sequence and function due to common ancestry
- not the same as syntany
69
Where do human homologues exist?
- yeast
- worms
- fruit flies
- bacteria
70
What is the major clue to gene and protein function?
recognition of sequence similarity
71
Gene sequences are more _____________ than genome structure
tightly conserved
-size of genome, number of genes, size of introns, and abundance of repetitive sequences can be quite different
72
Number of genes only roughly correlated with ________ complexity of organism
phenotypic
73
Where does phenotypic complexity arise from?
duplication and expansion of related gene families
74
How do genomic changes occur?
as mistakes in DNA replication and repair
75
How many nucleotide pairs is randomly changed in the germ line every million years?
1/1000 nucelotide pairs
rare occurrence
76
What may also play a role in mistakes in DNA replication and repair?
movement of transposable elements
77
What DNA changes can occur?
- base pair substitiutions
| - large scale rearrangements
78
What are 4 large scale rearrangements?
- duplications
- deletions
- inversions
- translocations
79
What does comparative genetics do?
reconstructs genome evolution by comparing genomes of contemporary organisms
80
What are 2 reasons for sequence conversion?
- not having much time for mutations to occur since lineages separated
- purifying selection
81
What does purifying selection mean?
elimination of mutations that interfere with important genetic functions
82
Small size genome is due to small ________
introns
83
Small size genomes lack _________
repetitive DNA
84
Intron position of huntingtin gene is __________ compared to the human gene
conserved
85
________% of human genome is conserved
5%
86
Only ________% of the human genome codes for proteins
1.5%
87
Little selective pressure is needed to maintain __________ genes
mutation-free
88
What are pseudogenes?
duplicated gene that has become irreversibly inactivated by multiple mutations
89
What is gene duplication and divergence?
both copies remain functional while diverging in sequence and pattern of expression
90
What gave rise to "a" and "b" globin genes?
duplication and mutation
91
What moved the "a" globin gene to a separate chromosome?
translocation
92
What resulted in more specialized "b" globin molecules?
further duplication and mutation
93
Human sequences vary ______% from one to another
0.1%
94
Human and chimps differ _____%
1%
95
Majority of human sequence variations are neither _______ or _______
harmful or beneficial
96
What type of mutations can become fixed in a population?
neutral mutations
97
What are SNPs?
- single nucleotide polymophisms
- points in the genome where one group has one molecule and another group has another
- variation occurs at high rate (1%)
98
What are CNVs?
- copy number variants
- presence of many duplications and deletions of large blocks of DNA
- some blocks common, others rare
