Lecture 17 - Mitochondrial Dna

Front 1

What is extranuclear inheritance?

Back 1

inheritance patterns involving genetic material outside the nucleus

Front 2

Mito and chloroplasts contain

These organelles are found in the

therefore extranuclear inheritance is also termed

Back 2

Dna

cytoplasm

cytoplasmic inheritance

Front 3

The genetic material of the mito is located in a region called?

Back 3

nucleoid

Front 4

The genome of organellses usually consists of a singular _______ chromosom

Back 4

circular

Front 5

A nucleoid may contain several copies of the ________

the organelle contains many____________

a cell contains many _________
therefore there are numerous copies of organellar _________ per cell

Back 5

genome

nucleoids

organells

genome

Front 6

T/F: Sizes of the mito genome in selected organisms are very diverse

Back 6

t

Front 7

Whats more stable: circular mtDNA or linear mt DNA

Back 7

circular

Front 8

Circular DNA is present at a thousand times higher copy number than linear. T/F

Therefore the mito DNA can be sometimes sequenced from _______ samples

Back 8

True

extinct

Front 9

Give examples where mtDNA was sequenced from extinct samples

Back 9

wolly mammoth and world trade center

Front 10

What theory descrices the evolutionary origin of organelles?

Back 10

endosymbiotic theory

Front 11

The theory holds that encestral eukaryotic cells grew _____ and lacked ________ and chloroplasts.

These early cells engulfed an aerobic _____-_______bacterium which evolved into a ________.

Back 11

anaerobically , mito

alpha- proteo, mitochondrion

Front 12

Likewise, endocytosis of a photosynthesizing bacterium led to the evolution of modern eukaryotic cells with mito and ________.

Back 12

chloroplasts

Front 13

Mitochondria uses ___. This provides a great advantage for ______ production.


Chloroplasts allow fixation of ________ from the air.

Back 13

O2, ATP

CO2 (carbon)

Front 14

Evolution of mito genomes:

During evolution, how did the organellar genomes gotten smaller? 2 basic mechs

Back 14

transfer of genes to nuclear genome
loss of genes that were no longer requird

Front 15

mOST MITO PROTEINS ARE ENCODED BY GENES IN THE ________

tHESE PROTEINES ARE FIRST MADE IN THE_______ THEN TRANSPORTED TO THE MITO

tHE HAVE MITO TARGETING SIGNALS IN THERE __________ TERMINAL ENDS

Back 15

nucleus, cyto, amino

Front 16

Mito DNA has a ______ mutation rate than nuclear DNA.

This makes it useful in the study of close evolutionary __________ within species.

Examples Mitochondrial Eve and Out of africa hypothesis describes?

Back 16

higher, relationships

hypotheses of human origin and migration

Front 17

The mito genetic code differes in a _____ codons from the nuke code.


UGA usuall encodes stop but in mito it encodes:

AUA usually isoleucine but in mito:

AGA usually arginine but in mito:

Back 17

stop, in mito tryptophan

methionine


Vetebrate mito - STOP
drosophilia mito - SERINE
Yeast mito - arginine

Front 18

The 22 human mito tRNA are all encoded in the __________ genome and have expanded _________.

Back 18

mitochondria, xpanded

Front 19

Does the mito genome have histone prots?

Back 19

no

Front 20

Does it have pre-mRNA introns?

Back 20

No

Front 21

Polycistronic DNA?

Back 21

YES

Front 22

5' cap added to mRNA?

Back 22

NO

Front 23

3' POLY A til added to mRNA?

Back 23

some animals

Front 24

Shine delgarno sequence in 5" UTR of mRNA?

Back 24

RARE

Front 25

NON UNIVERSAL CODONS AND EXTENDED WOBBLE?

Back 25

YES

Front 26

The human mtDNA consists of _____ bp?

It only carries _____ genes:

___ rRNAs
____ tRNAs
____ mRNAs that encode polypeptides functioning in oxidative phosphorylation to make ATP

Back 26

16569
37
2
22
13

Front 27

human mtDNA is high _________ in organization.

it is replicated by DNA polymerase ______

there are few ________ regions

There are no _________. (budding yeast mtDNA has 2 ______-________ group II introns)

Back 27

economical

gamma, non-coding, introns, self-splicing

Front 28

Human mtDNA is circular or linear?

Outside strand is called?

Inside strand is called?

_____ strand codes for only ____ protein and 8 ______.
tHE PROTEIN IT ENCODES IS CALLED ______?

wHAT KIND OF GENES ARE FOUND ON MTDNA? 3 KINDS

Back 28

circular

heavy strand H

light strand L

L, 1, tRNA, ND6

tRNA , PROTEIN, and rRNA genes

Front 29

Is the mechanism of mito DNA replication symmetric or assymetric?

Back 29

assymetric

Front 30

RNA primer initiates replication at origin on ___ strand.

After RNA synthesis of primer is initiated, RNA is ______ and ________ is syntheszed.

Synthesis of new ___ strand creats ____ loop by ________ parental strand.

__ loop then expands.

Back 30

H

degraded, DNA

L, D, displacement

D loop

Front 31

When the displaced strand passes origin on L strand, synthesis of new _____ strand starts.

Completion of new L strand releases _______ genomes

Back 31

H, daughter

Front 32

Review slide 18

Back 32

now

Front 33

the mtDNA replication machinery

the mito polymeras gamma is a _______trimer of one _______ subunit called gamma A and two ________ subunits gamma B. These increase processivity.

Back 33

hetero, catalytic, accessory

Front 34

What is the mitochondrial DNA helicase?

Back 34

ttwinkleeee

Front 35

Mitochondrial DNA mutations and repair systems

MAMMALIAN:

HAVE A _________ ____________ REPAIR SYSTEM
HAVE A ___________ REPAIR PATHWAY (O6-methylguanosine)
HAVE AN ALTERED ____________ REPAIR SYSTEM
HAVE THE _______ FOR RECOMBINATION REPAIR

DOES NOT HAVE __________ EXCISION REPAIR
WHICH MEANS THEY CAN NOT REPAIR THYMINE DIMERS EFFICIENTLY

Back 35

base excision
direct
mismatch
enzymes

nucleotide

Front 36

How many polycistronic messages cover the 2 strands in mito dna trascription?

Back 36

3

Front 37

Human mitochondrial DNA (mtDNA) has three promoters?.

The ___ promoter transcribes almost the entire heavy strand and the ___ promoter transcribes the entire light strand.

The ____ promoter causes the transcription of the two mitochondrial rRNA molecules: _____ AND ____

Back 37

H1, H2, and L SP (heavy strand 1, heavy strand 2, and light strand promoters)

H2, LSP

H1, 12S, 16S

Front 38

What cuts the rRNA and tRNA out from the polycistronic transcripts?

Back 38

RNAse P

Front 39

mitochondrial mrna lack ____ caps, 5' ____, __________ binding sites, and 3'_________.

most non mammalian also lack....

Back 39

5', UTRs, ribosomal, UTRs



poly-A TAILS

Front 40

ARE MITO RIBOSOMES MORE SIMILAR TO EUKARYOTIC OR BACTERIAL RIBOSOMES?

Back 40

BACTERIAL

Front 41

what kind of ribosomes do mitochondria have?

are they bigger than bacterial 70s ribosomes?

Back 41

55s

yes

Front 42

Mito ribosomes are mostly made of ________. How many?

Back 42

protein, there are 85 proteins compared to 53 in e. coli

Front 43

What percent of mito ribosomes are RNA?

Back 43

25%, compared to 65% RNA for bacterial ribosomes

Front 44

mito ribosomes bind to which codons at the end of mitochondrial mRNA?

Back 44

AUG, AUA (Met)

Front 45

Variations within mitochondrial DNA sequence give rise to ____________, defined as the presence of multiple distinct mitochondrial sequences within an individual.

Back 45

heteroplasmy

Front 46

there can be variable levels of heteroplasmy in mtdna in different tissues within the ______ individual

Back 46

same

Front 47

Mitochondrial mutations exhibit a ____________ effect.


Manifestations are produced only when the percentage of mutant mtDNA is above a certain___________.
___% - ___% mutant copies.

This varies depending on the tissue

Back 47

threshold,

threshold

60 - 80

Front 48

There is a close relationship between a mutant mtDNA and...

Back 48

aging

Front 49

mitochondrial DNA deletions accumulate in _________ and ________ with age. This plays a role in _____________ disease.

Also related to age-related loss in ________ mass called __________.

Back 49

brain, muscle, parkinsons

muscle, sarcopenia

Front 50

What stimulates the formation of the mtDNA deletions in brain and muscle with age?

Back 50

oxidative stress

Front 51

Common mito diseases:

Leigh Syndrome

_______ onset progressive n_____________ disorder.
Lesions are on one or more areas of the ___. (ex: brainstem, cerebellum)

there are defects in o____________ p___________ mitochondrial respiratory chain complexes. (Complexes I, II, IV, and V)

Mutations in mitochondrial ____ and _______ genes, and also __________ encoded subunits of oxidative phosphorylation.

Back 51

Early, neurodegenerative, CNS


oxidative phosphorylation

ND5, atp6, NUCLEAR

Front 52

Leber Hereditary Optic Neuropathy (LHON)

presents itsef in ______ as acute or subacute central vision loss which leads to blindness.

Most common in _____ around age ___.

___________ mutations in mtDNA (___ -->___ transitions)

leads to reduction in mito _________ production, which leads to dysfunction and death of the ______ nerve.

Mutations in at least four mitochondrial genes:


Mutations at basepairs 11778, 3460, 14484 in mtDNA accounts for 90% of prevalence.

Back 52

midlife

men, 20

Missense, G-->A

ATP, optic

ND1, ND4, ND4L, ND6 - Complex 1 of electron transport

Front 53

MELAS - mitochondrial encephalomyopathy lactic acidosis and strokelike episodes

________ inheritted disease

__________ neurodegenerative disorder

onset is between ages...

___ different mutations can cause MELAS

most common ________ mutation is A3243G of the my-tRNA leu gene

deficiency of complex 1 in _________ muscle

Back 53

maternally

progressive

2-15

17

point

skeletal

Front 54

MERRF - myoclonic epilepsy and ragged red fiber disease

_______system disorder that leads to generalized epilepsy, ataxia, weakness, dementia

hearing loss, myopathy, optic atrophy, and neuropathy can result


rare disorder 1 in 100,000

begins during _________ or __________. but can onset in ___________.

lethal in the absence of some amount of normal mito function

Back 54

multi

childhood, adolescence, adulthood

Front 55

Kearns-Sayre Syndrome (KSS)

_____-scale single deletions or ___________ of mtDNA, usually not ________.

occurs ________, probably at germ cell level or very early in embryonic development.

deletions vary in size from 1.1 to 10 kb and there are more than 150 different deletions associated with KSS.

deletions of 4977bp, known as the _______ deletion is most frequently encountered.

deletions are present in ___ tissues.

Back 55

large, rearrangements, inherited

spontaneously

common

all

Front 56

Chloroplast DNA is usually ________, but typically _______ than mtDNA.

have genes that encode for _RNA, _RNA, _______ genes, and unassigned ________.

Back 56

circular, larger,


rRNA, tRNA, protein, open reading frames (ORF)

Front 57

Sizes of chloroplast genomes do not vary in size as much as mtDNA. T/F

Back 57

true