Transcript Molecular III - Gene regulatory networks (ppt6)

Lecture 6 - Inheritance and change in DNA - Part II Meiotic Recombination
A. Evolution of Sex
•Evolution selected for DNA that itself was capable of
change from generation to generation.
•Inheritance (between generations) is typically NOT
through mito sis which would make clones of a parent.
•Instead, most organisms h ave sex. Why do we need sex?
•In a species, each gene can have many variations (usually
small mut ations) = alleles
•Highe r life has 2 copies of each gene. If two copies are
the same, then that locus/gene is homozygous. If the two
copies are different, then the gene is heterozygous.
•Theoretically, we only need one copy. Why do we have 2
copies then?
•Hypothesis:
The second copy allows allelic experimentation without
killing the organism
The second copy buffers the organism from deleterious
mutations.
Slide 6.2
Dominance and recessiveness - both alleles may encode proteins;
example - eye colour
-the gene that encodes the protein that "does the job" is dominant.
Allele A
Functional protein
Allele B
No protein or little protein
-most alleles are codominant (both proteins contribute to function)
-in agricultural breeding, many useful alleles are dominant, caused
by quantitative gain-of-function alleles (eg. disease resistance)
Because evolution favored having two alleles per gene, evolution
created sexes (male and female), each parent giving one copy to the
progeny (parent = P; progeny = F1)
Fig 18.24
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al.
WH Freeman and Co. Publishers, NY, 1996
Fig 5.1
Sex brings these two sets of alleles together.
Problem: To maintain 2 copies/gene in the progeny, each parent must
only contribute one copy of the two it has = meiosis
Slide 6.3
B. Meiosis and Meiotic Recombination
meiosis = the process of producing gametes that involves
reducing the allele number from two to one per gene to facilitate
inheritance via sex (demo showing duplication/reduction)
Mitosis
Meiosis
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Figure 5.2
WH Freeman and Co. Publishers, NY, 1996
Slide 6.4
Why is a genome divided into multiple chromosomes instead
of one large chromosome?
(demo of advantage of >2 chromos vs 1 chromosome)
Meiosis permits the independent assortment of genes because of the
existence of multiple chromosomes to allow the progeny to try out
new combinations of alleles. This is useful because many genes are
involved in producing a trait such as seed yield.
Independent assortment - for each chromosome pair, each gamete
can contribute the maternal or the paternal chromosome.
If two genes in a genome do not assort independently after meiosis
(from a sample of many meiosis), then the two genes are likely on the
same chromosome. In such a case, the two genes are said to be linked
In addition to mixing and matching entire chromosomes, evolution
selected for segments within chromosomes to be mixed and matched
= meiotic recombination demo
Chiasmata
Fig 19.3
Fig 19.1
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Chapter 19
WH Freeman and Co. Publishers, NY, 1996
Slide 6.5
For meiotic recombination to occur, the two chromosome pairs must
be aligned perfectly = chromosome pairing. This pairing is mediated
by precise recognition proteins that recognize homologous DNA
sequences and align them.
Fig 3.27
Fig 3.28
Synaptonemal
Complex
Proteins “zip”
the pairs
together
•The result of meiotic recombination is that blocks of genes
(chromosomal segments) are inherited intact from each parent,
NOT entire chromosomes.
•In the discipline of Genetics, it has been observed that the physical
distance between alleles of two linked genes ("map units" or
CentiMorgans, cM) is directly proportional to the number of meiotic
recombination events that occur in the gametes.
Fig 5.9
Fig 5.7
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Chapters 3 and 5
WH Freeman and Co. Publishers, NY, 1996
Slide 6.6
Map distances
between linked
benes
(m.u. = map unit)
Fig 5.10
Therefore, the percentage of "recombinants" that are recovered equals
the relative, physical map distance between the two genes. This
method (called "linkage mapping") is used to determine the order and
physical distances of genes on each chromosome. Once a gene has
been assigned a relative location on the chromosome
(relative to other genes), the gene is said to be "mapped".
Once a gene is mapped, it accelerates breeding and accelerates being
able to isolate ("clone") that gene.
A tomato linkage
map
Fig 5.15C
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al Chapter 5
WH Freeman and Co. Publishers, NY, 1996
Slide 6.7
Meiotic recombination allows new allelic block combinations to be
generated (demo with lethal flags)
Independent assortment and meiotic recombination are only useful
if different alleles exist.
Extremely different alleles can be found if the parents were
previously geographically isolated from each other and hence
developed independent sets of mutations.
Meiotic recombination allows blocks of alleles to be exchanged
between parental chromosomes -- this is the basis of breeding.
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Figure 5.21
WH Freeman and Co. Publishers, NY, 1996
C. Breeding
Sex between these two parents ("breeding") can bring the two sets of
alleles together. Sometimes, the F1 progeny resulting from the cross
between two geographically-diverse parents results in hybrid vigor,
which can increase yields (corn, rice, etc.) by >15%.
Small plant A x small plant B = large plant
The mechanistic basis of hybrid vigor is not understood and is very
controversial. Any hypotheses?
-each parent has different recessive, harmful mutations
-by crossing them, the progeny inherit a dominant, functional allele
for each locus (gene)
Slide 6.8
Meiotic recombination allows small chromosomal segments
containing useful genes (eg. disease resistance) to
be bred into locally adapted lines
Goal:
1 2 3 4
Local variety
Problem
Local x wild progeny = F1
50% = wild
1 2 3 4
Wild variety
disease
resistance
allele
Solution
Allow meiosis to recombine Disease R gene onto “local”
chromosome 2 background
Backcross recombined chromosome 2 to Local lines for
5-6 generations (BC1-BC6) to regenerate a nearly-pure Local
variety genetic background.
source: M.Raizada
Slide 6.9
Independent assortment and meiotic recombination are only
useful if different alleles ("genetic diversity") exist; otherwise
new combinations of alleles cannot be mixed up for breeding.
These alleles can come from diverse geographic populations
(such as from seedbanks) or they can be generated artificially
using chemicals or high energy radiation ("mutagens").
This is called mutation breeding, which has been practiced since
~World War II:
Fig. 15.30
Table 15.5
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Chapter 15
WH Freeman and Co. Publishers, NY, 1996
Slide 6.10
D. Evolution of genomes and the speciation of crops
Mistakes during meiosis contribute to large changes in genome evolution
and speciation, and have been critical to the evolution of crop species.
meiotic recombination involves breaking and pasting of chromosome
segments such that all genes are conserved. However, due to mistakes
in chromosome alignment or DNA repair, a block of a chromosome can
randomly break and reattach to itself or to other chromosomes resulting:
(demonstrations of)
What are each of these?
•tandem duplication
•deletion
•inversion
•translocation
•loss or gain of an
entire chromosome
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Figure 17.1A
WH Freeman and Co. Publishers, NY, 1996
These mistakes allow for genes to becoming duplicated (and initially
redundant), but then they mutate to create related, but novel genes
(through gradual spontaneous mutations). This is a way for gene
numbers to rapidly increase and create more complexity = gene families.
Slide 6.11
Change - Merging Entire Genomes at Fertilization
Mistakes in reproduction that permit the chromosomes from the
pollen and eggs from different species to unite can result in the
production of new species:
1 set of chromosomes = haploid
2 sets of chromosomes = diploid
4 sets of chromosomes = tetraploid
6 sets of chromosomes = hexaploid
bread wheat = hexapoloid - recent fusion of 3 species
pasta wheat = tetraploid - recent fusion of 2 species
modern corn = tetraploid - ancient fusion of 2 species
-because ancient, genes have diverged, so appeared
to be a diploid
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Figure 18.12
WH Freeman and Co. Publishers, NY, 1996
Figure 6.12
It appears as if most crop species have undergone multiple genome
fusions during the last 100 million years. This appears to be a common
way to rapidly recombine large numbers of different alleles together,
perhaps during periods of rapid or extreme environmental change.
Introduction to Genetic Analysis (6th ed)
A.J. Griffiths et al. Figure 18.11
WH Freeman and Co. Publishers, NY, 1996
Slide 6.13
***The result is that genomes are "a mess", an ancient
record of the mistakes in recombination, the fusion of
genomes, the gain and loss of blocks of chromosomes, and
many, many rearrangements*****
eg. Corn vs rice, highly related, though overall synteny, has
15,000 local chromosomal rearrangements
The rearrangements, duplications in the 5 chromosomes
of Arabidopsis thaliana (related to canola)
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
TAGI (2000) Nature 408, 796-814
Nature Publishing Group, U.K.
Slide 6.14
E. Lecture 6 - Summary of Concepts
Therefore, how did different crop plants and evolution of
higher plants evolve?
--New alleles for natural selection and breeding selection from:
-Point mutations
-Jumping Genes
-Segmental gene duplications
-inheritance or loss of entire chromosomes or entire genomes
-All of these recombine, mix and match, due to meiosis
(independent assortment of chromosomes) and meiotic
recombination (exchange of blocks within each chromosome)
•meiotic recombination with sex drives the mixing of blocks of
chromosomal DNAto generate new combinations of alleles
-- this is the basis of evolution and breeding
•alleles are inherited as chromosomal blocks
•the genome is not ordered, but messy, the result of mistakes in
DNA recombination, resulting in new genes
Questionnaire please
Slide 6.15