1. Extranuclear inheritance.

2. Lineage markers:
Y chromosome and mtDNA
Extranuclear inheritance

1. Organelle DNA inheritance

2. Infectious heredity: (HIV or Hepatitis C viruses)

3. Maternal effect

Drosophila development:

White dots = proteins form mRNA from

the mother.
 Extracellular Genomes:
• Set of hereditary information encoded in the
DNA of an organism, including both coding and
non-coding sequences

• Complete genetic information of an organism,

encoded by chromosomes and organelles DNA.

Human cells:
22 autosomal chr + X + Y + Mitochondrial
DNA (mtDNA)
Plant cell
• In plants: chromosomes + mitochondrial + chloroplast DNA

Circular DNA
Chromosomes

Circular DNA
Plants
Chloroplast DNA : 154 kb mtDNA : 367 kb

Source: http://edoc.hu-berlin.de/dissertationen/kuehn-kristina-2006-02-23/HTML/chapter1.html

Source http://www.ruhr-uni-bochum.de/pcp/JSchweer.html
mtDNA is smaller in animals

Human mtDNA: ~ 16.6 Kb

22 tRNA encoding regions

13 protein encoding regions
2 rRNA encoding regions
1 control region (~ 1200 bp)

Mutation rate is faster

in the control region
National Centre for Biotechnology Information (NCBI)

https://www.ncbi.nlm.nih.gov/nuccore/J01415.2?report=graph
Organelle inheritance
The DNA contained in chloroplast and mitochondria are
transmitted to the next generation through the ooplasm of the
maternal parent.

100s- 1000s of these genomes are present per cell.

All genomes within organelles are identical.

In rare cases mutations occur is one or many of them. As a result

the organisms carrying two or more different variants of the
organelle genomes is called heteroplasmic.

Heteroplasmy is frequent in humans.

It poses problems in forensic identifications
Origin of organelles:
Lynn Margulies
Endosymbiotic theory 1938-2011.

2 billion years ago: symbiosis with free- living protobacteria-

like organisms that were capable of aerobic respiration and
photosynthesis.

The genome of chloroplasts and mitochondria resembles

those of prokaryotic organisms.

The theory proposes that these bacteria were engulfed by

larger eukaryotic cells, and a beneficial symbiotic relationship
developed.
The chloroplasts of
Evolution of the host cell showed alterations, primary of which glaucophytes like this
Glaucocystis have a
was the transfer of many genes from the invading bacterium to peptidoglycan layer,
evidence of their
the nucleus of the host endosymbiotic origin from
cyanobacteria.
Source: wikipedia
Endosymbiosis, cont.
• Mitochondrial DNA (mtDNA) is
smaller than the DNA in chloroplasts,
introns are absent, and gene
repetitions are rare.

• Most of the protein encoding genes

are located on a single strand

• Replication in mitochondria is
dependent on genes encoded by
nuclear DNA

• This polymerase is sensitive to

bacterial antibiotics.
 mtDNA in humans

Properties Applications
• high copy number (Forensic DNA profiling of
degraded DNA)
• resistance to degradation
• maternal inheritance
• lack of recombination genealogy studies human history/
prehistory
• High mutation rate
higher m in control region forensic identifications

90 mummies mtDNA
genome sequenced
mtDNA inheritance ( Pedigree)

Source: http://www.kerchner.com/books/introg&g.htm
Pattern of inheritance of mtDNA
mtDNA mutation rates: Frequency with which a gene changes from the wild-type to a
specific mutant; generally expressed as the number of mutations per generation).

CR: fast mutation

rate
m = 10-3

Coding region, slow

mutation rate
m = 10-8
 Human mtDNA: control region
Haplotypes: defined by DNA sequence information in the ~1200 bp of the
control region, also called D-loop. Sections utilized in forensics are called
HVRI-II-III (Hyper Variable Regions)

m (mutation rate)
Control region has larger mutation rate

Control region:
µ~4 × 10−3 bp/generation

Coding region:
µ ~2 × 10−7 to 10−8 bp/generation
Image modified from http://www.familienforschung-rimek.de/dna-forschung/die-dna-und-das-ostpreussen-projekt
Mutations in human mtDNA
• Human mtDNA contains 16,569 base pairs coding for 13 of over 70
proteins required for aerobic cellular respiration.
• mtDNA is very susceptible to mutations, no histones (protective).
• Mitochondria have high concentrations of reactive oxygen species (ROS)
generated by cell respiration
• ROS (reactive oxygen species) damages organelle contents (proteins,
lipids, mtDNA)
superoxide

• A zygote receives a large number of organelles through the egg;

• a mutation in one or a few will be diluted out by many mitochondria that
lack the mutation and function normally
• During embryonic development, mutant mtDNA can concentrate in
certain tissues.
• Heteroplasmy is the condition in which adult cells have a variable mixture
of normal and abnormal organelles.
mtDNA haplotype

Individuals from the same maternal

family show identical haplotypes.

GenBank
NCBI Reference Sequence: NC_012920.1
Is used for annotation of mutations

Image from http://www.mtdnatest.com/reagents-kits/mtdnatest-human/

 mtDNA haplotype vs haplogroup
Haplotype: is a group of alleles carried by an
individual that are inherited together from a Ancestral mtDNA
single parent.

Haplogroup: is a group of similar haplotypes that

share a common ancestor with a single-nucleotide
polymorphism (SNP) mutation.
Human mtDNA: coding region
Slower mutation rate.
Some mutations are frequent or only
present in certain geographic regions,
and then provide information about
geographic origin of the group of people
sharing this mutation.

These are called Ancestry Informative SNPs.

AIl markers define HAPLOGROUPS.

These are shared by people living in the
same area or sharing the same ancestral
history (long-term pedigrees).
 mtDNA in perspective
L0d is predominant in southern Africa

Extracted from Behar et al (2008).

Correlation between geography and
genealogy: deep pedigrees with slow mutation
rate regions

http://en.wikipedia.org/wiki/Genetics_and_archaeogenetics_of_South_Asia
https://www.youtube.com/watch?v=yuT4IC1KXoc
Human mtDNA phylogenetic tree
(topology)

http://www.phylotree.org/tree/main.htm
 Interpreting phylogenetic trees
A phylogeny is a tree that shows the
evolutionary relationships among a group
of organisms

tip
node
Trees are constructed using information
Branch/ (characters).
node support
In the previous slides, the mtDNA tree
is constructed with DNA sequence
information.
root The characters that define branches or
tips are SNPs.
branch
The SNPs are either in ancestral or
derived state.
Phylogenetic information in trees
How tot construct a cladogram using
TIME GenBank

Clade- Short branch https://www.youtube.com/watch?v=OS

KwuOccAak
cluster

Closely related

distantly related

MRCA
(most recent
common ancestor)

Recent
Deep branch bifurcation
 Human Y-chromosome
60 Mb
PAR: Pseudo Autosomal region,
homology with X, pairing, recomb,
segregation
Non Recombining Region

SRY: SEX DETERMINING REGION.

Testis Determining Factor

Male Specific region of Y. 23 Mb

Some homology with X.
75 coding genes
NRY

(X chromosome: 900-1400 genes)

Y haplotypes and haplogroups

Haplotypes are defined according to a set of

microsatellites or Short Tandem Repeats
(STRs), expressed in # of repeats.

Haplogroups are defined by ancestry

informative SNPs, similarly to mtDNA.
Y-STRs
(Short Tandem Repeats or microsatellites)
• The forensic field has been dominated by the application
of STRs with mutation rate of 10-3 to 10-4

• In 2010: identification of markers with m > 10-2.

(RM-YSTRs, or Rapidly Mutating Y-STRs)

• m are expressed in # observed changes per # of meiotic

events.

• Related males have identical or very similar haplotypes.

 H
a
Y-chromosome SNPs p
l
o
g
r
o
u
p
s

Y-chromosome Haplogroups
 Out of Africa migration

Haplogroup A is the foundational haplogroup to all known patrilineal lineages which is largely restricted to
Africa.
Questions..
• What is extranuclear inheritance?
• How are mtDNA and chloroplast inherited?
• What are the characteristics of mtDNA?
• Why is mtDNA informative in the study of (human) evolution ?
• Why is mtDNA more prone to mutations than nuclear DNA?
• Explain the difference between haplotype and haplogroup
• What is a phylogenetic tree?
• What is the pattern of inheritance of mtDNA in a pedigree?
• What is the pattern of inheritance of the Y-chromosome?
links
http://evolution.berkeley.edu/evolibrary/article/phylogenetics_02

http://epidemic.bio.ed.ac.uk/how_to_read_a_phylogeny

http://www.biotechniques.com/news/Why-Do-Mitochondria-Still-Contain-
DNA/biotechniques-363872.html?autnID=343145#

Videos
mtDNA and human evolution http://www.youtube.com/watch?v=yuT4IC1KXoc