1. GENETIC
AN INTEGRATED APPROACH
A N A LY S I S
Chapter 19
Cytoplasmic Inheritance
and the Evolution of
Organelle Genomes
Lectures by Kathleen Fitzpatrick
Simon Fraser University
Mark F. Sanders
John L. Bowman
Copyright © 2012 Pearson Education Inc.

2. Covering sections
19.1, 19.2 & 19.5
P. 641-653, 662-670.

3. So far we have been talking about our
chromosomal genetic material….
IS THERE OTHER GENETIC
MATERIAL IN OUR CELLS
THAT WE DEPEND ON TO
LIVE?

4. Cross section of
Cross section of
Chlamydomamas
Chlamydomamas
showing three
showing three
cellular
cellular
compartments each
compartments each
with their own
with their own
genetic material:
genetic material:
nucleus (blue),
nucleus (blue),
mitochondria (red),
mitochondria (red),
and chloroplast
and chloroplast
(green)
(green)

5. 19.1 Cytoplasmic Inheritance Transmits
Genes Carried on Organelle Chromosomes
• Cytoplasmic inheritance refers to
transmission of genes on
mitochondrial and chloroplast
chromosomes, as opposed to
nuclear chromosomes
• In many eukaryotic species,
mitochondria and chloroplasts in
fertilized eggs are uniparental,
usually maternal, in origin
• In some species, cytoplasmic
organelles are contributed to the
zygote by both parents, i.e.,
biparental in origin

6. The Study of Cytoplasmic Inheritance Differs
from the Study of Nuclear Inheritance
• Individual cells may contain
multiple organelles
• Each mitochondria or
chloroplast may contain
multiple copies of its
chromosome
• The sizes, numbers, and
identity of genes in organelles
differs among species
• Trait controlled by cytoplasmic
inheritance can also be
influenced by nuclear genes

7. The Discovery of Cytoplasmic Inheritance
• Baur and Correns independently
discovered non-Mendelian
inheritance pattern in plants in
1908
• Correns studied leaf-color
inheritance in the four o’clock
plant
• He found that when flowers were
self-fertilized, the seeds produced
gave rise to plants with leaves of
the same color as the branch
(green leaves, white leaves, or
variegated leaves) upon which
the flower was found
stephgreenspace.blogspot.com

8. Results of Correns’ Studies
• Correns made reciprocal
crosses between flowers
on branches with
differently colored leaves
• The results of the tests
showed that progeny
invariably exhibited the
same phenotype as the
female parent in the cross
• This suggested that
transmission of leaf color
occurs by maternal
inheritance, through
genes transmitted in the
ovule only

9. Explanation for Maternal Inheritance
• In the 1950s, Chiba and
colleagues suggested
that mitochondria and
chloroplasts had their
own genomes
• This was based on
observation of Feulgenstained material in the
organelles; Feulgen
specifically
stains DNA

10. Homoplasmy and Heteroplasmy
•
The number of copies of the organelle genome per organelle can vary from one to many
• A cell or organism in which all copies of an organelle gene are the same is called
homoplasmic, or said to exhibit homoplasmy
• A cell or organism in which not all copies of an organelle gene are the same is
called heteroplasmic, or said to exhibit heteroplasmy

11. Homoplasmy and Heteroplasmy
Explain Maternal Inheritance of
Leaf-Color Phenotypes
• In Correns’ work, ovules from
variegated plants can produce
progeny with green, white, or
variegated leaves
• Ovules derived from
variegated branches may be
heteroplasmic; with
chloroplasts that can and
some that cannot produce
chlorophyll
• During meiosis and mitosis,
the chloroplasts are
segregated randomly into
daughter cells, so that
variegated, white, or green
progeny could be produced

12. Genome Replication in
Organelles
• Organelle DNA is
packaged into proteinDNA complexes in an
area called the
nucleoid
• Each nucleoid contains
multiple copies of the
organelle genome
• Replication of the
organelle genomes is
not tightly coupled to the
cell cycle

13. Factors Affecting Genome Replication in
Organelles
• Organelle transmission genetics depends on three factors:
1. The growth, division, and segregation of the
organelles themselves
2. The division and segregation of nucleoids in the
organelle
3. The replication of the individual organelle genomes

14. Variable Segregation of Organelle Genomes
• The variation in numbers of
organelles and their genomes can
influence the phenotypic effects of
mutant alleles of organelle genes
• Heteroplasmic cells can produce
heteroplasmic and homoplasmic
descendants
• If a mutation arises in a
chloroplast genome, chloroplasts
can arise in which all copies of the
genome harbor the mutation;
homoplasmic descendants can
occur by chance

15. Replicative Segregation
• Random
segregation of
organelles during
replication is
called replicative
segregation
• It can lead to
genetically
mosaic
organisms with
some mutant
cells and some
wild-type cells
• Homoplastic cells
can arise by
chance

16. Heteroplasmic Individuals & Disease
• In heteroplasmic
individuals,
penetrance and
expressivity depend
on the ratio of mutant
to wild-type alleles,
which can vary
among cells and
tissues
• The number of
chloroplast or
mitochondrial
genomes present in
germ cells influences
the ratio of mutant to
wild-type organelles
in the gametes

17. Mitochondrial Fusion and Fission
• Mitochondria have been observed to undergo frequent fusion and fission
• This creates the potential for individual mitochondria to have genomes of
mixed origin
• It also allows for the genomes of mitochondria within a cell to become
homogenized
• In contrast, chloroplasts do not usually undergo fusion
http://www.sciencemag.org

18. Mother-Child Identity of Mitochondrial DNA
• Mothers and all of their children share
identical mitochondrial DNA
• Mitochondrial DNA is used to find
matches between mothers and
offspring, or grandmothers and
grandchildren
• This was most dramatically used in
Argentina, to reunite kidnapped children
with their grandparents
• 1970s: Argentinean dictatorship
kidnapped and murdered political
dissidents. Pregnant women were
allowed to give birth before execution.

19. Mother-Child
Identity of
Mitochondrial
DNA
• Grandmothers of the
Plaza de Mayo
demanded return of their
adopted grandchildren
• Comparisons of
mitochondrial DNA
revealed exact matches
between individual
abuelas and specific
children of the murdered
women, allowing many
abuelas to be reunited
with their grandchildren,
whose mothers had
‘disappeared’.

21. Mitochondrial DNA Sequences and
Species Evolution
• Mitochondrial DNA sequences are
used as a tool for deciphering
genealogical history and
evolutionary relationships of
mammalian species
• Mitochondria are strictly maternally
inherited in mammals, with no
recombination of alleles
• Once a mitochondrial mutation
occurs in the germ cell of a
female, the mutation is transmitted
to all of her offspring; maternal
lineages can be traced back in
time and can allow identification of
a common ancestor

22. Mitochondrial Eve
• Analyses of mitochondrial DNA variation in
human populations has helped distinguish
between two models of human evolution and
migration. Looking for a Most Recent Common
Ancestor.
•
These results are very controversial.
•
The results only consider mitochondrial DNA!
•
Also looking at Y-MRCA (Most Recent Common
Ancestor, Male (Y))
•
Also looking at 6 Neanderthal genomes
• The multiregional (MRE) model suggests that
modern humans emerged gradually and
simultaneously from Homo erectus on different
continents
• The recent African origin (RAO) model proposes
that modern humans evolved from a small African
population that migrated out of Africa, displacing
other species
22

23. •
•
The MRE model suggests that
modern humans arose about 2
million years ago, and predicts
uniform genetic diversity among
most world populations
The RAO model suggests an
earlier origin (120,000 to 200,000
years ago), and predicts that
more genetic diversity should be
observed in the oldest
populations, in Africa

24. mtDNA Analysis Supports the RAO Model
• mtDNA analysis shows that African populations are most diverse and that
diversity elsewhere is based on a subset of African alleles
• Researchers determined an average rate of base changes in
mitochondrial DNA by comparing human and chimpanzee sequences
• Then they calculated the minimum divergence
time of humans, and obtained an estimate of ∼ 200,000 years
LIKE PHYLO! 

25. Mitochondrial Mutations and Human
Genetic Disease
• Mitochondrial mutations
can result in human genetic
diseases
• The phenotypes of such
diseases are often highly
pleiotropic, because of the
dependence of cells on
mitochondrial function
• Leber’s hereditary optic
neuropathy (LHON) causes
blindness in late
adolescence/early
adulthood; there are a
variety of pleiotropic
defects, including heart
abnormalities
25

26. Penetrance of LHON Is Not Complete
• In mitochondrial disorders
such as LHON, while all
affected children have an
affected mother, the converse
is not true
• There are three possible
reasons for incomplete
penetrance of the disorder: the
effects of heteroplasmy, the
influence of nuclear genes,
and the effect of environmental
factors
• In human pedigrees,
heteroplasmic mothers may
produce heteroplasmic or
homoplasmic (both types)
offspring

27. Mitochondrial Transmission in Mammals
• Human oocytes
typically have a few
large mitochondria
(∼10) that are later
divided into smaller
mitochondria,
representing up to
2000 mitochondrial
genomes
• This relatively small
number of original
mitochondria allows
for the possibility of
producing
homoplasmic
offspring that are wild
type

28. Replicative Segregation in
Somatic Cells
• Heteroplasmic individuals
undergo replicative
segregation in somatic
cells, which may lead to
variable wild-type :
mutant mitochondrial
ratios in different cells
and tissues
• Disease symptoms will
develop only if the tissues
that are vulnerable to the
disorder contain a high
proportion of mutant
mitochondria
• This will affect the
expressivity of the
disease

29. Mating Type and Chloroplast
Segregation in Chlamydomonas
• Chlamydomonas reinhardii is a singlecelled, haploid green alga with a single
large chloroplast containing 50 to 100
genomes, divided among 5 to 15
nucleoids
• Chlamydomonas cells of different
mating type, mt+ or mt−, produce diploid
cells that then undergo meiosis to
produce haploid progeny
• Both mating types contribute to the
cytoplasmic content of the zygote, but in
95% of matings, the chloroplast genome
is contributed by the mt+ parent

30. A Chloroplast Mutant in
Chlamydomonas
• The first mutation in a
chloroplast gene in
Chlamydomonas was
discovered by Ruth Sager
in 1954, and confers
streptomycin resistance
(strR)
• During mating, the two
cells of opposite mating
type fuse, and the
chloroplasts from each
parent fuse to form a
single chloroplast
• The mt− cell’s chloroplast
is usually eliminated; and
its genome is likely
degraded at some point
during mating

31. Elimination of One
Chloroplast
from the Zygote
• Reciprocal crosses between
resistance and sensitive
strains of each mating type
confirmed that the chloroplast
genotype is predominantly
contributed by the mt+ parent
• The mechanism for the
uniparental transmission is
unknown
• Chlamydomonas cells will
rarely show biparental
inheritance (5% of matings will
be biparental)
•
In this case, the presence of two
types of genomes in the same
organelle allows recombination
between them

32. Section 19.5
THE ENDOSYMBIOSIS THEORY

33. 19.5 The
Endosymbiosis Theory
Explains Mitochondrial
and Chloroplast
Evolution
• Endosymbiosis is a
mutually beneficial
relationship in which
one organism inhabits
the body of another
• Evidence indicates that
mitochondria and
chloroplasts are
descendants of freeliving bacteria that took
part in ancient infections
of eukaryotic cells
learn.genetics.utah.edu

34. Evidence for the Endosymbiosis Theory
• The double-membrane system
in chloroplasts and
mitochondria is derived from a
similar membrane system
found in bacteria
• The organelles are similar in
size to bacteria
• Organelle DNA is packaged
similarly to that of bacteria, and
differently than nuclear DNA

35. More Evidence for the Endosymbiosis
Theory
• The transcriptional and
translational machinery of the
organelles closely resembles
that of bacteria
• The protein-coding
sequences of organelle
genes are more like those of
bacteria than they are like
either nuclear genes of
eukaryotes or the sequences
of archaea

36. Evolution of Mitochondria
• Evidence indicates that
mitochondria are
monophyletic, all descended
from a single ancestor
• A single endosymbiotic
event gave rise to
mitochondria after a global
rise in atmospheric oxygen
that began 2 billion years
ago.
• The closest living relatives of
mitochondria are free-living
α-proteobacteria
• Extant α-proteobacteria
have larger genomes than
mitochondria, indicating
gene loss.

37. Evolution of Chloroplasts
• Chloroplasts are also monophyletic, descended from a single
endosymbiotic event at least 1.2 billion years ago
• The closest relatives of chloroplasts are free-living
cyanobacteria
• Existing cyanobacteria have much larger genomes than
chloroplasts, thus large-scale gene loss took place during the
evolution of chloroplasts

38. Animals && Fungi
Animals Fungi
Mitochondria and
chloroplasts are
monophyletic
-All descended from a
single common ancestor
Land plants and algae
Land plants and algae

39. • Many of the genes “lost” from chloroplast and mitochondrial genomes have been
relocated to the nuclear genome
• Nuclear genomes of eukaryotes show evidence of both ancient and recent DNA
transfer between organellar and nuclear genomes (more recently transferred
sequences will be more similar between nuclear and organelle genomes)

40. Approaches to Detecting
Organellar DNA Transfer
• Comparison between
Arabidopsis nuclear genome
and that of three
cyanobacteria species shows
that about 4300 nuclear
genes have a cyanobacterial
origin!
•
The importance of the enormous
amount of genetic information in
the evolution of eukaryotes is
difficult to overestimate!
• Comparisons between several
eukaryotic nuclear genomes
and α-protobacteria detected
at least 630 nuclear genes
derived from the
endosymbiont that gave rise
to mitochondria

41. Recent Transfers of Organelle Sequences to
Nuclear Genomes
• Recent transfers of mitochondrial
and chloroplast genes are included
in all nuclear genomes
• NUMTS are nuclear
mitochondrial sequences; these
are genes in the nucleus derived
from mitochondrial genomes
• NUPTS are nuclear plastid
sequences, genes in the nucleus
derived from plastid genomes
http://scienceblogs.com/digitalbio/2006/0
8/04/digital-biology-friday-hey-who/

42. Conclusions Based on Observation of
NUMTS and NUPTS
• Given the level of sequence similarity between NUMTS and NUPTS and their
respective organelle sequences, the transfers to the nucleus seem to be relatively
recent
• Entire organelle genomes were likely transferred to the nuclear genome multiple
times in evolutionary history
• The process is ongoing; DNA continues to move between the organelles and the
nucleus and the rate of transfer is surprisingly high
Arabidopsis
NUPTs
Chromosomes 1, 4, and 10 of Rice
NUMTs
NUPTs
NUMTs
Total number
301
572
677
566
Genic regions
79
166
177
138
Intergenic regions
222
406
500
428
Total number of
tight clusters
47 (151)
60 (288)
101 (467)
80 (367)
Homogenous
clusters
37
49
68
47
Heterogeneous
clusters
10
33
Mol Biol Evol (2004) 21 (10)

43. Encoding of Organellar Proteins
• Organelles contain many
more proteins than they
encode in their genomes;
most organelle proteins are
encoded in nuclei
• The nuclear-encoded proteins
are translated in the
cytoplasm and then
transported into the
organelles
• Organellar proteins are
targeted to their final
locations by signal
sequences, 15-25 amino
acids long at their amino
ends; different sequences
target the protein to different
locations within the organelle
http://dblab.rutgers.edu/paulinella/background.php

44. Encoding of Organellar Proteins, continued
• Contrary to expectation, not
all of the nuclear genes
originally derived from an
organelle are now targeted
to that organelle
• For example, in Arabidopsis,
less than half of the genes
originally from the
cyanobacterial
endosymbiont are targeted
to the chloroplast
• Conversely, a number of
proteins now targeted to the
chloroplast did not originate
in the cyanobacterial
endosymbiont

45. IF MITOCHONDRIA HAVE
THEIR OWN DNA, DO WE
NECESSARILY NEED TO GET
THEM FROM OUR MOTHER
OR FATHER?

46. Three Parent Babies!
https://www.youtube.com/watch
?v=jQxsW_H5qr4
• Nuclear DNA from the egg of woman carrying mitochondrial defects is
transferred into the enucleated cytoplasm of a donor egg that harbors
nonmutated mtDNA
• The egg is then fertilized in vitro by male sperm and then implanted in the
uterus of the mother with the mitochondrial disorder
• The resulting embryo will contain genetic information from three parents

48. Questions?