BIO SCI 97: Lecture 15 - Organellar Inheritance

organelles

specialized structures inside cells that perform particular functions

mitochondria

organelle responsible for producing much of the ATP that the cell uses for energy

organellar

_ inheritance describes how genetic material located in organelles is passed from parent to offspring

nuclear

_ inheritance: passing of genes located on nuclear chromosomes from parents to offspring

penetrance

the proportion of individuals with a particular disease-causing genotype that actually express the associated phenotype

partially penetrant

What inheritance pattern is most likely for this disease?

Baur

Erwin _ was a geneticist who studied inheritance patterns in plants, observing that plants had different leaf colors

Discovered that a plant had 3 types of branches with leaves: All green, all white, and variegated

chlorophyll

Green coloration in plants comes from _, a green pigment found inside chloroplasts

chloroplasts, sugars

_ are organelles responsible for photosynthesis, the process of using sunlight, CO2, and water to produce _ and O2

red, blue, green

Chlorophyll, the green pigment found inside of chloroplasts, absorb certain wavelengths of sunlight, particularly _ and _,

and reflect or transmit much of the _ light,

which makes plants appear green.

chloroplast DNA

Mutations in _ _ can interfere with chlorophyll production or chloroplast function, resulting in white regions of leaves

Nuclear, chloroplast

Relative to chlorophyll,

_ DNA encodes enzymes directly responsible for synthesizing chlorophyll,

while _ DNA encodes proteins important for chloroplast function (ex: photosynthesis, gene-expression machinery)

mutations

_ in chloroplast DNA may disrupt proteins needed for normal chloroplast development or function, indirectly preventing chlorophyll from accumulating. Without sufficient chlorophyll, the tissue may appear white.

reciprocal crosses

Erwin Baur performed _ _ by switching the leaf-color phenotypes of the maternal and paternal parents, finding that leaf coloration depended on the maternal branch, regardless of the pollen donor’s phenotype.

This differs from typical _ inheritance, where both maternal and paternal alleles can influence the offspring phenotype

nuclear, maternal

For the plants in Baur’s experiment,

The _ DNA of the maternal and paternal contributions are received by the offspring,

whereas only the _ chloroplast DNA is passed down to plant offspring

uniparental

_ inheritance means that genetic material for a particular trait is inherited from only one parent; this does NOT mean that the entire offspring inherits genetic material from only 1 parent

cellular respiration

the process of breaking down fuel/food molecules (glucose and fats) through enzyme-catalyzed reactions, releasing energy that cells use to produce ATP

• occurs in both the cytoplasm and within mitochondria

photosynthesis, sunlight

Chloroplasts perform _, using _ to convert materials such as water and CO2 into sugar and O2

eukaryotic

Mitochondria are found in nearly all _ cells, and perform _ _, the process of using energy from nutrients to produce usable ATP

DNA

Both chloroplasts and mitochondria possess _ and ribosomes, allowing them to produce some of their own proteins

sunlight, green

Chlorophyll is the green pigment in chloroplasts that absorbs _ for photosynthesis and makes leaves appear _

chloroplasts

In variegated branches, green and white regions occur because cells and tissues contain different distributions of functional and defective _

homoplasmy

all copies of a particular organellar genome within a cell are the same type

• can consist of all wild-type chloroplast DNA or all mutant chloroplast DNA

no

If there is a mutated DNA molecule, does that mean that the entire chloroplast it is in is nonfunctional?

yes

Can a cell be heteroplasmic if within it, each chloroplast contains only one DNA type (ex: 2 chloroplasts only contain wild-type DNA, and another 2 chloroplasts contain mutant DNA)?

each plant cell

Does heteroplasmy and homoplasmy refer to each plant cell, the branch/leaf, or each chloroplast?

yes

If you have one chloroplast in a cell that contains mutant and wild type DNA molecules, does this make the cell heteroplasmic?

heteroplasmy

_ is defined by the different organellar DNA genotypes present throughout the cell

nuclear, organellar

_ inheritance: In typical diploid cells, there are 2 copies of each autosomal gene

_ inheritance: In cells, there can be hundreds to thousands of copies of one gene per cell

randomly

When plant cell division occurs, chloroplasts and their DNA are _ distributed between daughter cells, meaning that daughter cells may have different proportions of wild-type and mutant chloroplast DNA

• A daughter cell can also receive more chloroplasts than the other daughter cell

homoplasmic

If a parent cell is homoplasmic for a particular chloroplast DNA genotype, its daughter cells will be _ for that genotype, regardless of how the chloroplasts are distributed during cell division

chloroplast

Heteroplasmy and homoplasmy describe the collective _ DNA genotypes across all *s within a cell

DNA, chloroplast

_ segregation can change the composition of individual chloroplasts, while

_ segregation can change the overall DNA composition of daughter plant cells

chlorophyll

If 50% of chloroplasts are green and 50% are white, it does not necessarily mean that the plant cell will be green and white;

Instead, the cell’s overall appearance depends on the total _ accumulation

uniparental

_ inheritance: a particular type of genetic material comes from only one parent

• ex: chloroplast DNA

nuclear, maternal

Although a son inherits his X-linked genes from his mother, he still inherits _ DNA from both parents through his autosomes and sex chromosomes.

In contrast, in Baur's experiment, chloroplast DNA is inherited exclusively from the _ parent, even though the offspring still inherit * DNA from both parents.

diploid, plant

In a typical _ cell,

there are 2 copies of each autosomal chromosome type, containing generally the same set of genes but potentially different alleles

In a _ cell, (can be diploid, polyploid, or haploid in gametes)

there may be many chloroplasts or mitochondria, each of which contain multiple copies of its own DNA genome and each genome contains the same sets of genes, which might also have different alleles or mutations

• ex: might contain 100 copies of a particular chloroplast gene, with 70 wild type copies and 30 mutant copies

heterozygosity, heteroplasmy

_ refers to having two different alleles of a nuclear gene on homologous chromosomes,

whereas _ refers to having different organellar DNA genotypes among the multiple organellar genome copies within a cell (2 or more organellar genotypes among many copies present in a cell)

nucleoid

a region of an organelle where organellar DNA is packaged with proteins, and does not have its own surrounding membrane.

Each can contain one or more copies of the organellar DNA genome

• Both chloroplasts and mitochondrion can have several of these

epistatic

• Nuclear gene: Functional and contributes to chlorophyll production.

• Chloroplast gene: Mutated, disrupting an essential function needed for normal chlorophyll accumulation.

• Result: Even though the nuclear gene is functional, the chloroplast mutation prevents the expected green phenotype.

Thus, the chloroplast gene is _ to the nuclear gene because its mutation masks the nuclear gene’s phenotypic effect

nuclear, organellar

Organelles require proteins encoded by both _ and _ DNA to function normally

gene

Even if a chloroplast contains mutant DNA molecules, if there are enough functional _ products, the chloroplast is able to function properly and accumulate chlorophyll, appearing green

independently, once

Organellar DNA replication and organelle division occur _ of the nuclear cell division cycle, meaning that multiple rounds of either process can occur before the cell divides or at different times.

In contrast, nuclear chromosome DNA replication typically occurs _per cell cycle during S phase, in preparation for cell division.

random segregation

how DNA copies are distributed during organelle division

DNA, chloroplast

Random segregation of _ molecules during chloroplast division,

followed by random segregation of _ during plant cell division,

can ultimately produce daughter cells with different proportions of WT and mutant chloroplast DNA.

less

When a daughter cell inherits many organellar DNA copies, random segregation is less/more likely to result in that cell receiving only one DNA genotype, assuming both genotypes are reasonably common (50% WT and 50% mutant for example)

mitosis, independently

Nuclear chromosomes during _ replicate during S-phase, are segregated using the mitotic spindle (precisely-controlled chromosome-segregation system), and daughter cells normally receive the same chromosome complement (get both homologous chromosomes)

Organellar DNA replicates _ of nuclear S phase, organelles and DNA copies are distributed less precisely, and daughter cells receive different proportions of mutant and wild-type DNA

x-linked, mitochondrial

X-linked and mitochondrial genes inheritance patterns are different because:

In ____ inheritance, the genes follow sex-chromosome inheritance,

whereas in ____ DNA inheritance, it is normally inherited from the mother by children of either sex

both, one

The zygote receives nuclear DNA from one/both parent(s), and receives mitochondrial DNA from one/both parent(s)

egg, sperm

The egg/sperm supplies essentially all the cytoplasm and mitochondria to the embryo, and the egg/sperm mitochondria may enter the egg but are generally eliminated or prevented from being transmitted

DNA

A “mutant mother” would mean that all organellar _ copies in her cells carry the mutant genotype

genotype

genetic makeup, referring to the genetic version at one gene (alleles) or of an entire genome (wild type DNA sequence vs. same genes with one mutation)

replicative segregation

the process by which the proportions of mutant and wild-type organellar DNA change over successive cell divisions (replication occurs in DNA too, where additional copies are unequally distributed among organelles and daughter cells), potentially allowing a mutation that started in one DNA molecule to become more common in certain cell lineages

replicative segregation

A mutant organellar genome can spread and eventually result in a homoplasmic cell via _ _

100%

If there is a homoplamic mutant mother that is affected by a condition, and she is crossed with an unaffected father, what % of the offspring will be affected?

can, cannot

In X-linked inheritance, fathers can/cannot pass x-linked alleles to their daughters,

In mitochondrial inheritance, fathers can/cannot transmit mtDNA

daughters

Mitochondrial inheritance pedigree:

Both sons and daughters inherit their mother’s mitochondrial DNA, but only sons/daughters normally pass that mitochondrial DNA to the next generation

mother’s

A male can have a mitochondrial genotype completely different from his partner’s (due to variation in his mitochondria from his own mother), and marry a female with her own mitochondria inherited from her mother.

However, all of the offspring will only receive the mother’s/father’s mitochondrial DNA, regardless if the offspring are male or female

No

An affected grandmother carries mutant mitochondrial DNA, and she transmits that DNA to her children, regardless if male or female

Will the affected sons pass down their mutant mitochondrial DNA to their own children?

females

All _ who inherit the mutant mitochondrial DNA from the mutant grandmother can pass it to their offspring, regardless whether children are male or female

cannot, can

A father can/cannot transmit mitochondrial disease through his mtDNA, but he can/cannot transmit nuclear DNA mutations that cause mitochondrial dysfunction

Therefore, not all mitochondrial diseases follow maternal inheritance

maternally

Human genetic diseases caused by mitochondrial DNA mutations are _ inherited

However, even if an offspring inherits mutant mitochondrial DNA from their mother, whether the disease is expressed or how or where depends on several factors

ancestral

_ lineage: a line of descent connecting individuals to a common ancestor

In terms of mitochondrial DNA transmission, the father’s _ lineage ends with him because he inherited maternal mtDNA, thus belonging to his mother’s maternal lineage, but cannot transmit that mtDNA to his children

maternal

A _ lineage refers to a line of ancestry traced through successive generations of mothers, where individuals are connected via their mothers across generations

mitochondrial

_ DNA is passed down through the maternal lineage, which scientists can use to identify and trace maternal ancestry

ancestry

refers to an organism’s biological origins through previous generations

• your biological origins - the ancestors you descended from and the relationships connecting you to them across generations

  • includes your grandmother, mother, father, grandfather, and other biological ancestors

• your overall biological history

lineage

A _ traces a particular chain of biological descent connecting an individual to their ancestors across successive generations.

genome

One reason mitochondrial DNA is easier to use for studying ancestry than nuclear DNA is its smaller _, which makes sequencing and comparing DNA between individuals easier, helping scientists investigate ancestral biological relationships; thus making studying ancestry easier

maternal

Mitochondrial DNA is particularly useful for tracing _ lineages because mitochondria (and their DNA) are generally transmitted from mother to offspring.

recombination

The lack of _ makes mtDNA useful for studying maternal ancestry because its sequence is transmitted relatively unchanged across generations, except for mutations, making ancestral relationships easier to trace without the complication of recombination.

mutations

_____ introduce differences in mitochondrial DNA sequences that help researchers distinguish maternal lineages. If every individual had identical mitochondrial DNA, researchers would not be able to differentiate between different maternal lineages or branches of a family tree using mtDNA alone.

ancestors

Researchers found that certain Indigenous American populations and populations from Siberia/northeastern Asia had similar mitochondrial DNA sequences and shared mtDNA variants, providing evidence that their maternal lineages descended from shared ancient maternal _

• branches formed by ancient maternal ancestor from descendants, and some descendants remained in Asia, and others migrated into the Americas

  • mtDNA sequences retained shared variants, despite additional accumulation of mutations

function

The protein complexes in the inner mitochondrial membrane involved in the electron transport chain contain proteins encoded by both nuclear DNA and mitochondrial DNA (mtDNA). Therefore, mutations in either genome can disrupt mitochondrial _.

nuclear

A vast majority of proteins necessary for mitochondrial function are encoded by _ DNA,

while _ DNA encodes a small but essential subset of proteins involved in energy production

oxidative phosphorylation, ETC, hydrogen, ATP

Mitochondria are primarily responsible for ATP production through _ _

This process consists of:

1. Nutrients are broke down before this process, in glycolysis and the citric acid cycle, producing high energy electron carries (NADH and FADH2)

2. The electrons enter the _ in the inner mitochondrial membrane

3. As electrons move through the ETC, energy is released and used to pump _ ions from the mitochondrial matrix into the intermembrane space

4. H+ flows back into the matrix through ATP synthase, using energy from this flow to produce _ from ADP and inorganic phosphate

5. Oxygen acts as the final electron acceptor in the ETC

krebs cycle

Cellular respiration includes glycolysis, pyruvate oxidation and the Krebs cycle, and oxidative phosphorylation

However, the mitochondria participates in both the _ _ and oxidative phosphorylation

Krebs

_ cycle (citric acid cycle): A process that occurs in the mitochondrial matrix and extracts energy from fuel-derived molecules, capturing most of that energy in high-energy electron carriers (NADH and FADH₂).

• Fuel-derived molecules are molecules obtained from breaking down nutrients in food (e.g., carbohydrates are digested into glucose).

• Glucose undergoes glycolysis to produce pyruvate.

• Pyruvate undergoes pyruvate oxidation to produce acetyl-CoA.

• Acetyl-CoA enters the Krebs cycle, where its acetyl group is oxidized, and energy is captured primarily in NADH and FADH₂.

• These electron carriers then deliver high-energy electrons to the electron transport chain for oxidative phosphorylation (ATP production).

heteroplasmy

Two individuals with the same mtDNA mutation may experience different disease severity, or no disease at all, because factors such as _ (where rather than having different DNA genotypes like mutant and functional, there may be different proportions of mutant and normal mtDNA) influence mitochondrial function

dysfunction

Because many different tissues depend on mitochondrial ATP production, mitochondrial _ can affect multiple parts of the body and produce different symptoms depending on the affected tissues’ functions

ATP

Cells in different tissues depend on mitochondria to produce _ for their specific functions (cells require this to be made to carry out their function) Therefore, mitochondrial dysfunction can impair cellular function, potentially disrupting tissue and organ function if enough cells are affected

pleiotropy

_ refers to one gene affecting multiple phenotypic traits

pleiotropy

A mother can pass mutant mtDNA to her offspring or a spontaneous mutation can occur during embryo development, which can then be distributed among different tissues during embryonic development. These tissues may contain different or similar proportions of mutant mtDNA, potentially causing mitochondrial dysfunction and different phenotypic abnormalities depending on the affected tissue (e.g., muscle weakness and vision problems caused by the same mtDNA mutation). This is an example of _____.

LHON

a mitochondrial disease caused by mtDNA mutations that impair oxidative phosphorylation, particularly affecting cells of the optic nerve

• this mutation can be present in other tissues as well, but retinal ganglion cells are particularly sensitive to its effects due to its high energy demand and other cellular characteristics

partial penetrance

LHON is a mitochondrial disease that demonstrates _ _, meaning that some children carrying the mutation may not display the disease-associated phenotype, which may be a result of various factors:

1. Different proportions of mutant mtDNA in children

2. Which tissues have more mutant mtDNA - so less in the optic nerve cells means less likelihood of disease-development

3. Nuclear genetic factors

4. Environment

homoplasmic

Although LHON commonly involves homoplasmic/heteroplasmic mtDNA mutations, this is not required nor sufficient for disease development

homoplasmy

_ refers to the uniformity of mtDNA genotypes, and you can discuss it at the cellular, tissue, or even individual level

• generally, an individual who is * for a particular mtDNA mutation has that mutation in essentially all their mtDNA copies throughout the body; it just cannot be confirmed for every cell, since scientists typically examine only certain tissue samples rather than every body cel

incomplete penetrance

An individual can be homoplasmic for a LHON-associated mutation, meaning that essentially all of their mtDNA carry that mutation, including mtDNA in their optic nerve cells, but the individual may never develop LHON. This demonstrates _ _

homoplasmy

_ in terms of mutations means that the mitochondrial DNA copies have the same genotype (in other words, the same mutation across mtDNA copies)

threshold

_ effect: whether the proportion of mutant mtDNA is high enough to cause noticeable dysfunction

occurs when the proportion of mutant mtDNA is low enough, mitochondrial function may remain sufficient to meet a cell's energy needs, preventing the disease-associated phenotype. However, when the proportion of mutant mtDNA exceeds a certain * , mitochondrial function may become insufficient, causing cellular dysfunction and potentially disease symptoms.

egg

The mitochondrial bottleneck occurs during _ development in the mother and helps explain why her different eggs can contain different proportions of mutant mtDNA

oocytes

_ are developing and immature egg cells, which are formed by germline cells in the mother’s developing ovaries

amplification

_ increases the number of mtDNA copies in the developing oocytes as it matures, while approximately maintaining the proportion of mutant to normal mtDNA

fertilized

When the egg is _, it develops into an embryo, and its mtDNA is distributed among developing cells and tissues

• the proportion of mutant mtDNA can differ among those tissues, influencing penetrance and expressivity in offspring carrying the mutation

• higher proportions of mutant mtDNA in one tissue may increase the likelihood of mitochondrial dysfunction, depending on the mutation and that tissue’s energy requirements

bottleneck

The mitochondrial _ helps create differences in mutant mtDNA proportions between eggs because only a small effective sample of maternal mtDNA contributes to each developing oocyte

DNA

Germline cells physically pass their mt _ to descendant cells during division, and that can subsequently replicate; so, the original cell no longer exists as one separate cell and has divided into daughter cells

heteroplasmy

Different levels of _ can contribute to both incomplete incomplete penetrance and variable expressivity in mitochondrial diseases

Leigh

_ syndrome: a progressive neurological disorder, involving mitochondrial dysfunction, that commonly begins in infancy or early childhood, which can affect brain and nervous system function, muscle control and movement, feeding and swallowing, breathing, and development

• can be life-threatening in early childhood

mutation

Leigh syndome is not defined by one particular _, but it is defined by a characteristic pattern of neurological problems and brain abnormalities that can result from different genetic mutations - either in nuclear DNA or mtDNA - that impair mitochondrial dysfunction

Leigh

_ syndrome can result from different genetic mutations that impair mitochondrial function. The mutation causing * syndrome can be present in the DNA of cells across multiple tissues. Although multiple tissues may be affected, the effects depend on factors such as the proportion of mutant mtDNA and the energy requirements of each tissue. However, certain brain cells are particularly vulnerable because of their high energy demands, so mitochondrial dysfunction can cause especially severe effects in these cells