Lect. 2 - DNA, chromosomes and Genomes 2

Question 1

epigenetics

Answer 1

a form of inheritance that is superimposed on the genetic inheritance based on DNA

Question 2

What are some examples of epigenetics?

Answer 2

DNA methylation, chromatin structure (inherited from parental to daughter cells after cell division), and histone modification

Question 3

heterochromatin

Answer 3

chromatin that is very condensed - stains darkly throughout the cell cycle, even in interphase. thought to be late replicating and genetically inactive; contains very few genes and those that are present are resistant to gene expression

Question 4

where is heterochromatin highly concentrated?

Answer 4

at centromeres and telomeres

Question 5

position effect

Answer 5

activity of a gene depends on position on chromosome - will be silenced if relocation near heterochromatin

Question 6

euchromatin

Answer 6

all the rest of the chromatin that is less condensed

Question 7

example of gene silencying from Drosophila

Answer 7

breakage events that bring heterochromatin near active genes tends to silence them, zone of inactivation spreads a different distance in different cells; evidence that heterochromatin when positioned next to genes can silence them and is not localized to one area

Question 8

histone modifications

Answer 8

aa side chains of histones are subject to a variety of covalent modifications; occurs on the core of the histone as well as the tail

Question 9

what is the effect of acetlyation of lysines on histones

Answer 9

the chromatin structure is loosened; added by histone acetyl transferases (HATs) and removed by histone deacetylase complexes (HDACs)

Question 10

What is the mechanism of the mono,di and tri-methylation of lysines?

Answer 10

added my methyl transferases; removed by histone demethylases

Question 11

In histone modification, what determines how/when/if gene expression takes place?

Answer 11

the types of proteins the modified DNA attracts

Question 12

variant histone proteins exist for each core histone except for which?

Answer 12

H4

Question 13

variant histone proteins

Answer 13

present in much smaller amounts than core histones and are less well-conserved;

Question 14

major histones

Answer 14

synthesized during S-phase and assembled into nucleosomes on daughter DNA helices just behind replication fork

Question 15

When are variant histone proteins synthesized?

Answer 15

during interphase and inserted into already-formed chromatin. Requires histone exchange process catalyzed by chromatin remodeling complex

Question 16

Histone Code

Answer 16

thousands of combinations of modifications (methylation, acetylatoin, etc) may exist; further diversity is created by variant histones; code has specific meaning for cell, determining how/when DAN is packaged in nucleosome

Question 17

What reads the histone code?

Answer 17

code reader complez; involves joint recognition of histone tail and covalent modificaitons; code can change as the cell needs change

Question 18

H3 modifications to N-terminal tail

Answer 18

reading histone code involves joint recognition of marks at other sites on nucleosome along w/ tail recognition; few meanings known

Question 19

modified chromatin can spread

Answer 19

after modifying enzyme marks one or few neighboring nucleosomes, chain reaction can ensue; code reader-writer enzymes spread the mark over chromosome

Question 20

Chromatin remodeling

Answer 20

complexes also contain an ATP-dependent chromatin remodeling protein - all work together to either condense or decondense long stretches of chromatin as reader moves along

Question 21

What halts the spread of chromatin modifications?

Answer 21

several mechanisms: physical and enzyme barriers; HS4 region - protects the Beta globin locus from silencing, contains a cluster of histone acetylase binding sites

Question 22

What do centromeric heterochromatin contain?

Answer 22

centromere specific H3 histone, CENP-A, and other proteins that pack the nucleosomes into defense arrangements to form the kinetochore, a structure required for attachments of the mitotic spindle.

Question 23

What do centromere sequences in humans consist of?

Answer 23

short repetitive DNA sequences called alpha satellite DNa

Question 24

Alpha satellite DNA

Answer 24

defined by assembly of proteins, not DNA sequence: alpha satellites are found at non-centromeric positions in the genome

Question 25

Neocentromeres

Answer 25

new centromeres that can form spontaneously on fragmented chromosomes, some of which lack alpha satellite DNA

Question 26

Inheritance of chromatin structures

Answer 26

de novo centromere formation requires a "seeding event" on alpha satellite DNA; H3-H4 tetramers are directly inherited by the daughter strands at the replication fork; once formed, it is directly inherited in each round of replication

Question 27

what are the largest chromosomes known?

Answer 27

lampbrush chromosomes from amphibian oocytes - can be visualized by light microscopy

Question 28

structure of interphase chromosomes

Answer 28

series of large chromatin loop emanating from a linear chromosome axis

Question 29

Which would be more likely to be being transcribed; the DNA closer to the axis or the DNa in the chromatin loops?

Answer 29

loops - b/c they are more available

Question 30

What does heterochromatin preferentially associate with?

Answer 30

nuclear lamina

Question 31

What property does the interior of the nucleus have?

Answer 31

very heterogeneous

Question 32

How are different activities localized in the nucleus?

Answer 32

Different "neighborhoods" have effects on gene expression; distinct biochemical environments have high local concentrations of enzymes and molecules for specific processes - DNA repair foci & RNA synthesis

Question 33

Mitotic Chromosomes

Answer 33

Highly condensed; final level in chromosome packing; 2 daughter DNA molecules replicated in interphase are separately folded to produce two sister chromatids

Question 34

What is the purpose of condensation?

Answer 34

disentangelment of sister chromatids to allow separation for cell division and protection of fragiles DNA molecules as separation occurs

Question 35

Condensins

Answer 35

proteins that aid compaction; use ATP hydrolysis to coil the DNA molecules into chromatids; major structural component of the core of every metaphase chromosome

Question 36

Homologues

Answer 36

genes that are similar in both sequence and function due to common ancestry; human homologues exist in yeast, worms, fruit flies and bacteria

Question 37

Which is more tightly conserved, gene sequences or genome structure?

Answer 37

Gene sequence; size of genome, number of genes, size of introns, abundance of repetitive sequences can be quite different

Question 38

How do genomic changes occur?

Answer 38

as mistakes in DNA replication and repair; rare; 1/1000 nucleotide pairs is randomly changed in the germ line every million years; movement of transposable elements also play a role

Question 39

Comparative genomics

Answer 39

reconstruct genome evolution by comparing genomes of contemporary organisms

Question 40

What are reasons for sequence conservation?

Answer 40

not having much time for mutations to occur since lineages separated; purifying selection

Question 41

purifying selection

Answer 41

elimination of mutations that interfere with important genetic functions

Question 42

Genome size can vary considerably

Answer 42

puffer fish genome = 0.4 billion base pairs compared to 1 billion in other fish; small size due to small introns - lacks repetitive DNA

Question 43

pseudogenes

Answer 43

a duplicated gene that has become irreversibly inactivated by multiple mutations

Question 44

duplication and divergence

Answer 44

both copies remain functional while diverging in sequence and pattern of expression; globin gene gamily derives from common ancestral gene

Question 45

SNPs

Answer 45

single nucleotide polymorphisms; points in the genome where one group has one nucleotide and a different group has another; variation occurs at a high rate (1% or more)

Question 46

CNVs

Answer 46

copy number variants; presence of many duplications and deletions of large blocks of DNA; some blocks are common and others rare; significant of most is unknown