Genomic conflict and genomic imprinting

Lukas Schrer
Evolutionary Biology
Zoological Institute
University of Basel

23.10.2013

Advanced-level Evolutionary Biology

The green-bearded placenta

a placenta

a green beard

a green-bearded
placenta

an idea of Haig 1996

Summary: Genomic conflict and genomic imprinting

genomic conflict
an attempt to clarify the terminology
transposable elements
cytoplasmic genetic elements
cytoplasmic male sterility

genomic imprinting
the kinship hypothesis
imprinting of growth factors in mouse
double fertilisation in plants

the green-bearded placenta

Genomic conflict

genomic
conflict

interlocus sexual
conflict

intralocus
sexual conflict

Rice & Chippindale 2001

Genomic conflict
genomic conflict is genetic conflict within an organism
genomic conflict can occur within or between genomes of an individual
organisms are composed of different genomes and genetic elements
intracellular symbionts
e.g. Wolbachia

supernumary chromosomes
e.g. B chromosomes

extracellular symbionts
e.g. zooxanthellae
transposable
elements

+ chloroplasts

Genomic conflict
conflict arises at reproduction for primarily two reasons
because not all genes are transmitted in the same way
some cytoplasmic organelles, symbionts and sex chromosomes are transmitted
by only one sex

because not all offspring inherit the same set of genes

genes that can bias fair meiosis have a transmission advantage

there is scope for a conflict between the genetic and individual level
of selection
remember the t-haplotype in mice

Genomic conflict
genes that cause such genomic conflict are called selfish genetic
elements (also selfish DNA, ultra-selfish genes, genetic parasites)
can be harmful for the individual
disruption of gene function, meiotic drive, sex-ratio distortion, male sterility

this should lead to the evolution of restorer and suppressor genes

therefore many of these kinds of conflicts may not be visible under normal
conditions, but may only appear if distant populations are crossed

Transposable elements
transposable elements
usually occur in multiple
copies in the genome
they make up about 35% of the
mammalian genome

two main types

retro-elements or -transposons
DNA elements

transposable elements can

replicate within the genome
this increases the chances that
they are actually transmitted to
the offspring

from Pomiankowski in Keller 1999

Transposable elements
transposable elements are selfish genetic elements because they can
lower the fitness of the host
transposable element insertion is probably one of the major causes
of spontaneous mutation in natural populations
>50% of mutations in Drosophila

if transposition occurs into a coding or regulatory sequence this

usually disrupts normal gene function

Transposable elements
several traits suggest that transposable elements have evolved
strategies to reduce harm to the host
transposition usually does not occur in somatic cells as this would also harm the
transposable elements, but does not increase transmission
some transposable elements (group I introns) can self-splice out of messenger
RNAs, leading to a readable mRNA and translation into a functional protein
the P element of Drosophila codes for two proteins, a transposase and an
inhibition factor, and because the inhibition factor is maternally inherited the
transposable elements only transposes when P-carrying males are crossed to
females without P elements
because they are sensitive to the cellular environment in which they reside,
transposable elements may actually become involved in regulatory functions

10

Transposable elements
DNA methylation may be involved in the silencing
of transposable elements (Kakutani et al. 2005)
in plants, mutations that disrupt DNA methylation can
lead to aberrant phenotypes that that are stably inherited
over many generations, even if the mutant plants are backcrossed into a wild-type background
in Arabidopsis thaliana the ddm1 mutation (decrease in
DNA methylation) leads to the uncontrolled release of
many transposable elements because the mutation leaves
the genome insufficiently methylated
transposition of these transposable elements then leads
to mutations that are stably inherited

11

Cytoplasmic genetic elements

cytoplasmic genetic elements do not segregate as precisely as the
nuclear genes (no fair mitosis or meiosis)
such elements include mitochondria, chloroplasts, and intracellular symbionts

if during normal cell division one daughter cell obtains too few
cytoplasmic genetic elements, this is adjusted by subsequent
multiplication of these elements
so if a mutation occurs in a cytoplasmic genetic element, then the
competitively superior form is expected to spread
however, if the same mutation is detrimental to the (asexual) host,
this mutation will not spread in the population

12

Cytoplasmic genetic elements

during sexual reproduction cells containing different cytoplasmic
genetic elements fuse so genetically different cytoplasmic genetic
elements can meet in one cell
during subsequent cell divisions sampling errors will lead to
different mixes of these cytoplasmic genetic elements in the
different cell lineages that form in the embryo
these cell lineages can then be expected to compete to obtain
access to the germ-line
cytoplasmic genetic elements that are successful in this competition
may spread in the population, even if this harms the individuals
carrying them

13

Cytoplasmic genetic elements

a solution to this genomic conflict is to impose uniparental
inheritance of cytoplasmic genetic elements
uniparental inheritance often occurs via the female function
probably the female function because, due to anisogamy, it contributes many
more cytoplasmic genetic elements to the zygote than the sperm
in contrast, the relatively small contribution by sperm is sometimes actively
labelled with ubiquitin for degradation (e.g. mitochondria)

interestingly, uniparental inheritance of cytoplasmic genetic

elements also occurs in isogamous species
there it is usually linked to the mating type of the zygote

uniparental inheritance effectively prevents (or at least strongly

reduces) this type of genomic conflict

14

Cytoplasmic genetic elements

but uniparental inheritance leads to a new type of genomic conflict
under uniparental inheritance males are an evolutionary dead-end
elements that can bias the investment of resources towards the
female function will have a transmission advantage
there are many examples of such biases, which are variably called cytoplasmic
incompatibility, male killers, induced parthenogenesis and feminization

nuclear restorer genes are expected to appear to counteract these

biases, and sex chromosomes may partly have this function

15

from Werren et al 2008

Cytoplasmic male sterility

about 5% of angiosperms are gynodioecious
populations consist of hermaphrodites and females
females can be considered to be male-sterile hermaphrodites

male sterility is usually caused by mitochondrial mutations

due to a trade-off between resource allocation to the male and female function
these mitochondria have a higher fitness

cytoplasmic male sterility is an important tool in crop plants

because of the sex allocation trade-off male-sterile plants generally have a higher
yield, because making fewer pollen allows them to make more seeds
male-sterile plants are easier to cross with a high-yield paternal genotype,
because the own pollen does not interfere
and for the same reason male-sterile plants are easier to hybridise (used, for
example, in the sugar beet Beta vulgaris)

16

Cytoplasmic male sterility

the interaction between male-sterility mutations and nuclear
restorers was shown in Plantago coronopus

a hermaphroditic and male-sterile

flower of Plantago coronopus

17

a spike of Plantago coronopus

Koelewjin 2003

Cytoplasmic male sterility

crossed different strains so that offspring
vary in the number of restorer alleles
the number of restorer alleles correlates
with the sex ratio in the population
investment in male and female function
changes with the sex ratio

18

from Koelewjin 2003

Genomic conflict

genomic
conflict

interlocus sexual
conflict

19

Rice & Chippindale 2001

Genomic imprinting
genomic imprinting is parent-oforigin-specific gene expression
i.e. the expression of a gene depends on
whether it was inherited via the father or
via the mother

occurs in about 80 mammalian genes

most of these genes are in some way
linked to resource uptake and growth

genomic imprinting is not restricted

to mammals, but it also occurs in
some invertebrates and plants

20

intralocus
sexual conflict

Genomic imprinting
kinship theory of genomic imprinting (Haig 2004)
parent-specific gene expression evolves at a locus because a genes level of
expression in one individual has fitness effects on other individuals who have
different probabilities of carrying the maternal and paternal alleles

what is required is conflict over the level of postzygotic investment

between asymmetric kin
e.g. mother vs. offspring
an offspring is (almost) certain that its maternally derived allele is present in the
mother (unless there has been a mutation or mix-up) and it is (almost) certain
that its paternally derived allele is absent in the mother (assuming outcrossing)

e.g. offspring vs. offspring

in multiply mated females the offspring are less related in their paternal than
maternal inherited alleles

21

Genomic imprinting
in mammals genomic imprinting occurs primarily in genes involved
in mother-foetus interaction and lactation
but effects may also occur after weaning

the father can gain a fitness benefit by inducing its offspring to ask
for more resources from the mother than she may be willing to give
(unless there is strict life-long monogamy)
the mothers future reproduction is not important to the father (similar to male
manipulation in other sexual conflict traits)
the mother should try to silence such genes (e.g. by changing the state of
methylation via an epigenetic modification)

this leads to the evolution of genomic imprinting

'demand' genes are only expressed when inherited via the father
'defense' genes are only expressed when inherited via the mother

22

Genomic imprinting
imprinting of growth factors in mouse
the insulin-like growth factor 2 (Igf2) is
expressed in the foetus and promotes the
acquisition of resources from the mother
across the placenta
! the paternal copy of Igf2 is expressed, but
the maternal copy is inactive
the insulin-like growth factor 2 receptor (Igf2r)
appears to inhibit the action of Igf2
! the maternal copy of Igf2r is expressed, but
the paternal copy is inactive

experimentally tested
mice with an inactivated Igf2 attain only 60% of
the normal birth weight
mice with an inactivated Igf2r have a 30% higher
than normal birth weight
23

Genomic imprinting
genomic imprinting probably prevents parthenogenesis in mammals,
because parthenogenetically produced zygotes would lack the
(effects of the normally) paternally expressed genes
could this maybe explain why parthenogenesis is sperm-dependent
in many planarians?

24

Genomic imprinting
most well-understood examples come from mammals
how would this work in the sex-role reversed sea-horses?

25

Genomic imprinting
plants may also have genomic imprinting
a maternally dominated tissue is responsible for
the provisioning of the growing embryo and seed

a look at fertilisation and seed set in plants

the 3N endosperm is the link between the

2N mother plant and the 2N embryo
26

The green-bearded placenta

green-beard genes
signal their presence in an organism (feature)
detect the presence in another (perception)
help the carriers of such genes (response)

such a gene would be expected to spread

through the population even if it harms some of
the individuals carrying it
the term green-beard gene was coined by
Dawkins (1976), but the mechanism was
conceived by Hamilton (1964)

27

The green-bearded placenta

in placental mammals green-beard genes
may be involved in mother-foetus
interactions (Haig 1996)
in a heterozygous mother only 50% of the
offspring inherit a given allele
if an embryo could signal to the placenta that it
has inherited the allele, the maternal allele could
increase provisioning to that particular embryo
this could occur at a cost of the other embryos
(and thus the mother)
! gestational drive
the green-bearded placenta

28

The green-bearded placenta

cadherin genes, which are involved in
cell-cell contacts, have all the
necessary traits
cadherins have homophilic interactions
(feature and perception)
cadherins lead to good cell-cell contact and
are involved in gene activation (response)

so if cadherin genes can be involved in

gestational drive the evolution of
suppressors is expected, leading to
(rapid) antagonistic coevolution

29

The green-bearded placenta

a recent study provides preliminary evidence for this hypothesis
the authors tested for positive selection (using the dN/dS ratio
approach) on the evolution of cadherin genes
three different cadherins (E-, P- and VE- cadherin), which are all
involved in maternal-foetal interactions, showed at least some signs
of positive selection
one cadherins (H-cadherin), which is not expressed in the placenta,
did not show any signs of positive selection

30

Summers & Crespi 2005

The green-bearded placenta

Amino Acid!
Met!
Trp!
Asn!
Lys!
Asp!
Glu!
His!
Gln!
Tyr!
Cys!
Phe!
Ile!
Stop!
Pro!
Gly!
Ala!
Thr!
Val!
Arg!
Ser!
Leu!

Codons
ATG
TGG
AAT!
AAA!
GAT!
GAA!
CAT!
CAA!
TAT!
TGT!
TTT!
ATT!
TAA!
CCT!
GGT!
GCT!
ACT!
GTT!
CGT!
TCT!
CTT!

AAC
AAG
GAC
GAG
CAC
CAG
TAC
TGC
TTC
ATC!
TAG!
CCC!
GGC!
GCC!
ACC!
GTC!
CGC!
TCC!
CTC!

ATA
TGA
CCA!
GGA!
GCA!
ACA!
GTA!
CGA!
TCA!
CTA!

CCG
GGG
GCG
ACG
GTG
CGG!
TCG!
CTG!

AGA!
AGT!
TTG!

AGG
AGC
TTA

31

Summary: Genomic conflict and genomic imprinting

genomic conflict
an attempt to clarify the terminology
transposable elements
cytoplasmic genetic elements
cytoplasmic male sterility

genomic imprinting
the kinship hypothesis
imprinting of growth factors in mouse
double fertilisation in plants

the green-bearded placenta

32

Literature
Mandatory Reading
none

Suggested Reading
Pages 206-213 of Chapter 9 on Genomic Conflict in Stearns & Hoekstra
(2005). Evolution: An Introduction. 2nd Edition. Oxford University Press
Haig (1996) Gestational drive and the green-bearded placenta. Proceedings of
the National Academy of Sciences USA 93: 6547-6551

Books
Burt & Trivers (2006). Genes in Conflict: the Biology of Selfish Genetic Elements.
Harvard University Press, Cambridge, MA.

33