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Chapter
7. Non-Mendelian Inheritance
Most
genes follow a Mendelian pattern of inheritance, however many do not.
In
this chapter we will discuss:
Maternal
effect and epigenetic inheritance.
Genotype does not
directly govern phenotype as predicted by Mendel.
Look
at the effects of the timing and inactivation of gene expression.
Non-Mendelian
inheritance due too DNA not located in the nucleus.
Maternal
Effect.
An inheritance
pattern of nuclear genes in which the genotype of the mother directly
determines the phenotype of the offspring.
Genotypes of the
father and offspring do not affect the phenotype of the offspring. Explained by an accumulation of gene products that the mother provides to the developing eggs.
Ex: dextral
(right handed) or sinistral (left handed) shell and internal organ
arrangement of Limnea peregra (water snail).
dextral
(right handed) is more common and dominant to sinistral (left handed).
This
pattern of organization results from the cleavage pattern of the egg
immediately following fertilization.
Reciprocal crosses were done with homozygous snails and the results did not show Mendelian
inheritance.
Either
reciprocal cross resulted in offspring with the maternal phenotype.
Sturtevant examined
this data in the 1920s and concluded it was a maternal effect.
He reached his
conclusions from examining the F2 and F3 generation.
The F2
should have had a 3:1 phenotype ratio and instead was all dextral. The F3 generation shows a 3:1 ratio of dextral to sinistral because of a homozygous recessive mother.
Female
gametes receive gene products from the mother which affect early
development of offspring.
Maternal effect can
be explained by oogenesis in female animals.
The oocyte, which
will become haploid, are surrounded by nurse cells which supply it
with nutrients.
Example: If the
nurse cells were heterozygous for the snail coiling maternal effect gene.
The
egg would then receive both D and d gene products.
These
gene products last long after fertilization occurs into embryonic
development..
Since
the egg received D gene product even though the egg was only d it will
develop dextral shell and organs.
Now
if we think about the experiment we know that a DD mother would only give
D, a dd mother would only give d, but a Dd mother would transmit either D
or d but with D and d gene product. »
Researches have
found that maternal effect genes encode for proteins important in the
early steps of embryogenesis.
Caenorhabditis
elegans is used to study development (along with Drosophila)
because this nematode is transparent and you can actually follow
(visualize) an individual cells in development.
Epigenetic
Inheritance.
This is
the modification of the expression of a nuclear gene but is not
permanently changed over generations.
These changes will
happen on an individual basis over an organisms lifetime but will not be
passed on.
Dosage compensation
occurs to offset the number of sex chromosomes.
So
males and females have the same levels of gene expression early in
development.
Genomic Imprinting
involves a change in a single gene or chromosome in gamete formation.
Depending
on whether the modification occurs in spermatogenesis or oogenesis it will
result in the offspring expressing the gene inherited from the mother or
father.
Dosage
compensation is necessary to ensure genetic equality between genders. Expression of many genes on the sex-chromosomes especially on the X-chromosome is equal in both males and females despite the difference in gene numbers.
Example: X-linked
apricot eye color in male and female Drosophila.
The
hemizygous male and homozygous female have the same apricot eye color.
If
one of the females apricot eye color genes is deleted or nonfunctional the
female apricot eye color becomes paler.
This
shows that the female flies two genes are giving the same phenotype as the
males one copy.
This
is consistent with dosage compensation.
Not
all genes show dosage compensation and the reason for this is unknown.
How does this occur?
In
some organisms like Drosophila the expression of X-linked genes in the
male flies is increased two fold.
In
mammals one of the X-chromosomes in somatic cells is inactivated often the
paternal X.
In
humans the paternal or maternal chromosome is randomly inactivated
throughout the females body.
A
structure found in the somatic cells of female mammals called the Barr
body and is actually a highly condensed X-chromosome.
This
mechanism of inactivation known as the Lyon hypothesis is illustrated in
calico cats and variegated mice.
The
female mouse receives alleles for black fur from one parent and white fur
from another and one allele is randomly shut off in each developing cell
due to X-inactivation (Barr bodies) giving eventual rise to patches of
white and black fur. »
These
Barr bodies are highly compacted so most their genes cannot be expressed.
X-inactivation
in mammals depends on the Xic locus.
Mammalian cells
possess the ability to count the number of X-chromosomes and inactivate
any number above one.
A site on the
X-chromosome called the X-inactivation center or (Xic)
appears to play a critical role.
Counting is
accomplished by seeing how many Xics the cell has. Pseudoautosomal genes are not affected by X-inactivation.
Imprinted
gene expression depends on the gender of the parent which transferred the
gene.
Imprinting implies a
marking process that has memory.
Segment of DNA is
marked and the mark is retained throughout the life of the organism.
Leads to
non-Mendelian inheritance because the offspring will not express both
alleles
The
expression is based upon the gender of the parent who passed on the
allele.
Example: Mouse Igf-2
A gene encoding for an Insulin like growth factor. This gene is essential for normal growth.
A mutant allele of
this gene (Igf-2m) results in dwarfism, however the dwarfism
depends on whether the mutant allele was passed on by the male or female
parent.
Imprinting of the Igf-2
gene occurs so that the maternal allele is not expressed.
The
only way that the mouse will be dwarf is if it inherits the Igf-2m
gene from the male parent.
Imprinting
can be broken down into different stages: Establishment of the imprint during gametogenesis, imprint maintenance during adulthood and erasure and reestablishment of imprint in germ cells.
The offspring get
imprinted (inactive) genes from the mother and active genes from the
father.
The offspring then
maintain these active/inactive genes for their lifetime.
When producing their
own gametes the females inactivate any Igf-2 allele it is passing
on and the male activates all alleles of Igf-2 it is going to pass
on.
Imprinting
plays a role in the inheritance of two human genetic disorders Angelman
syndrome (AS) and Prader-Willi syndrome (PWS).
PWS is characterized
by reduced motor function, obesity and mental deficiencies.
AS is characterized
by repetitive muscle movement, seizures, hyperactivity and mental
deficiencies. Both are most commonly due to a small deletion on chromosome 15.
If it is inherited
from the mother it is Angelman syndrome, paternal inheritance leads to PWS.
To explain this
researchers have proposed that this region contains two closely linked but
distinct genes that are maternally or paternally imprinted.
One gene is
maternally expressed if it is deleted from a maternally inherited
chromosome 15 then AS will result.
A different gene is
paternally expressed if it is deleted from the paternally inherited
chromosome 15 then PWS will result.
Extranuclear
inheritance.
The most
biologically important involves genetic material in cellular organelles.
Since the
organelle and DNA is outside the nucleus it is called extranuclear or
cytoplasmic inheritance.
This
genetic material contains genes that encode for proteins that function
within these organelles.
Mitochondria
and chloroplasts contain multiple copies of circular chromosomes; each
chromosome carries several genes.
1951 Japanese
researcher Y. Chiba was the first to suggest that chloroplast had their
own DNA.
Visualized
the DNA with the DNA specific stain Feulgen.
Mitochondrial and
chloroplast chromosomes have been further characterized with the advent of
molecular genetics and electron microscopy. The genetic material of these organelles is located in a region called the nucleoid.
The genome is
composed of a single circular chromosome.
Each organelle may
have multiple nucleoids each with multiple copies of the chromosome.
Ex:
Mice each mitochondrion has 1-3 nucleoids, each with 2-6 copies of
the chromosome.
The size of the
mitochodrial and plastid genomes vary among species and organisms.
Animals
small; plants large.
Human mtDNA
is 17,000 bp and is 1% the size of a bacterial chromosome.
The functional role
of the gene products of the mitochondrial chromosome is ATP production.
Many
of the genes required for photosynthesis.
Tobacco
chloroplast chromosome.
156,000
bp.
Many important
proteins involved in the function of chloroplast and mitochondria are
encoded for in the nucleus these proteins have special targeting sequences
that help them get to the correct organelle.
Extranuclear
inheritance produces non-Mendelian results in reciprocal crosses.
Mitochondria and
plastids do not segregate into gametes the same way chromosomes do.
Carl Correns (1909)
studied leaf pigmentation in Mirabilis jalapa.
Leaves
were either white green or variegated.
He
used reciprocal crosses and found females passed on the leaf pigmentation,
maternal inheritance of plastids.
The
inheritance pattern of mitochondria and plastids varies from species to
species and depends on gender.
Mitochondria and
chloroplast are often inherited from the mother in heterogamous species.
The
mothers gamete is large and gives most the cytoplasm to the new zygote.
The
males gamete is small barely more than a nucleus. 1-4/100,000 mitochondria in mice are inherited from the father.
Rare human
diseases are caused by mitochondrial mutations.
Since mitochondria
show maternal inheritance these diseases show strict maternal inheritance
as well.
Lebers
hereditary optic neuropathy-
Mutation in one of several genes involved in cellular respiration. »
ND1,
ND2, CO1, ND4, ND5, ND6 or cytb
Neurogenic
muscle weakness-
Mutation in the ATPase6 gene that encodes for a subunit of the
mitochondrial ATP-synthetase.
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