ZOO 4910 Lecture Notes - Lecture 6: Down Syndrome, Chromosome Segregation, Aneuploidy
2 May 2018
School
Department
Course
Professor
Chromosome
•
DNA sequence on the chromosomes
•
Haploid
!
Diploid
!
Triploid
!
Tetraploid
!
Ploidy -number of sets of chromosomes
○
Genome
•
Genomic Perspective of Evolution
Specialized cell division
•
Reduces chromosome number by half (--> sperm and eggs)
•
Aneuploidy
○
Trisomy 21
○
Missing X chromosome (turner syndrome)
○
When things go wrong:
•
Bananas -triploid
•
Cause of ~15% of human miscarriages
○
Most of the time aneuploidy leads to death
!
If the organism does survive, they are usually
sterile
!
In extremely rare circumstances, the mutant can
survive and reproduce
!
When the organism survives:
○
Improper chromosome segregation --> diploid gametes
•
Recall: Meiosis
Autopolyploidy -two chromosome sets derived from one
species
•
Allopolyploidy -two chromosome sets derived from different
species (tabacco)
•
Changes in Ploidy Level
Surfeit of males (75%)
○
Sex determination makes duplication less viable
•
It is much more common in plants (up to 30-80% are
polyploidy)
•
Polyploidy events are rare in animals
308 chromosomes
•
Docosaploid -22n (black mulberry)
Heterosis -increase in performance (like hybrid virility)1.
Gene Redundancy -mask deleterious alleles; tolerant of
inbreeding
2.
Asexual reproduction possible3.
Benefits of Polyploidy:
*all these traits make for excellent founder species
Susumu Ohna (1970)
•
Evolutionary complexity is mediated by polyploidy
•
1R and 2R whole genome duplications -
500-900mya
!
This occurred twice in the common ancestor of all
vertebrates
○
Third round of duplication occurred in teleost fish
lineage (300mya)
○
Whole genome duplication (WGD) in vertebrates:
•
Time when gene sequences diverged
○
Transpositions
○
Segmental duplications -part of a chromosome
○
Tandem duplications -single genes or small DNA
regions
○
Phylogenetic interference for duplicated gene origins:
•
Different duplicate gene pairs originated around the
same time (~350mya) -date duplication through
phylogenetic analyses
○
Synteny segments of human genes on two different
tetraodon chromosomes
○
Proposed model for the distribution of ancestral
chromosome segments in the human and
tetraodon genomes
!
The composition of tetraodon chromosomes is
based on their duplication pattern whereas the
composition of human chromosomes is based on
the distribution of orthologues of tetraodon genes
!
*see slide
○
Evidence of teleost 3R WGD:
•
WGD -sudden doubling of every chromosome caused a
drastic change to the genome
○
Diploidization -the major evolutionary process
following WGD
○
Evolution after WGD:
•
Pseudogenes -genes that mutate and lose function
○
Subfunctionalization -partitioning of ancestral gene
functions among the duplicates
○
Neofunctionalization -one of the duplicates acquires a
novel functino
○
4 way recombination at meiosis
○
Like pairs with like
!
Neat and tidy process
!
In a diploid genome:
○
Too much similarity for neat and tidy process
!
Sometimes like pairs with like
!
Sometimes like pairs with 'almost like'
!
In tetraploid genome:
○
Evolutionary Consequences of WGD:
•
Evolution by Gene Duplication
Chromosomes come in different shapes and sizes
•
Acrocentric -at end
○
Metacentric -in middle
○
Fused acrocentric -end of one chromosome when fused
with another
○
Centromere is the tightly wound portion where spindle fibers
bind to pull pairs apart
•
Two metacentric homologues --> bivalent ring
○
Four metacentric homologues -->tetravalent ring
○
Traditional pairings:
•
A -normal chromosome pairing of 2 metacentrics
(bivalent ring)
○
B -normal pairing of 2 acrocentrics (bivalent rod)
○
C -4 way pairing with 2 acrocentrics and 2
metacentrics (multivalent rod)
○
D -4 way pairing of 4 metacentrics (multivalent ring)
○
*see viewing mitosis in a salmonid:
•
Quick Review: Chromosome Types
Evolution following 1R, 2R and 3R WGD proceeded to the
point where the chromosomes behave as two diploid pairs (no
4 way recombination at meiosis)
•
Contain a 4th WGD
○
'in between stage' of genome evolution
○
Pseudotetraploid -4 way recombination does happen
but is uneven
○
Faster in some places, slower in others
!
Evolution back to diploid state appears uneven
○
4 way recombination -large chromosome is a
prerequsite
○
Does the structure of the genome affect which regions
evolve back to diploid the fastest?
○
Salmonid specific whole genome duplication:
•
Chromosome structure and diploidization:
Homology -shared ancestry in DNA sequence
○
Homeology -chromosomes with shared ancestry within
species (result of duplication)
○
Comparison of DNA sequence within and across species:
•
Advances in WGD study:
Algorithm to find regions of similarity between sequences
(DNA, RNA and protein variants)
•
Lets researchers determine probability that two sequences
evolved from a common ancestor
•
Salmonids on Basic Local Alignment Search Tool (BLAST)
More acrocentrics than other salmonids (~28 pairs)
•
More ancestral karyotype than other salmonids
•
Arctic Char Karyotype:
Question: Does the structure of the genome affect which
regions evolve back to diploid the fastest?
•
Hypothesis: chromosome structure and 4-way recombination
causes the rate of diploidization to vary across the genome
•
Duplicate markers will be found near the telomeres of
chromosomes in higher frequency
1.
Duplicates will be found less on acrocentric homeolog
pairs
2.
Predictions:
•
4508 arctic char linkage map markers
○
1130 duplicate markers
○
Arctic Char Linkage Map:
•
Telomeres are the slowest diploidizing regions
○
Within chromosomes, more duplicate loci are preserved at
telomeres
•
No 4 way recombination
○
Diverge faster
○
Significantly lower numbers of duplicates markers on
acrocentric sets
•
More exchange
○
Within chromosomes, more duplicate loci preserved at
telomeres
•
Salmonid Diploidization:
Genome duplication allows for large scale evolutionary
changes
•
'back up copy' of every gene alleviates selection against new
mutations
•
Evolution after whole genome duplication is a messy process
•
Conclusions:
Genome Duplication & Subsequent
Evolution in Vertebrates
Friday,)September) 22,)2017
12:21)PM
Chromosome
•
DNA sequence on the chromosomes
•
Haploid
!
Diploid
!
Triploid
!
Tetraploid
!
Ploidy -number of sets of chromosomes
○
Genome
•
Genomic Perspective of Evolution
Specialized cell division
•
Reduces chromosome number by half (--> sperm and eggs)
•
Aneuploidy
○
Trisomy 21
○
Missing X chromosome (turner syndrome)
○
When things go wrong:
•
Bananas -triploid
•
Cause of ~15% of human miscarriages
○
Most of the time aneuploidy leads to death
!
If the organism does survive, they are usually
sterile
!
In extremely rare circumstances, the mutant can
survive and reproduce
!
When the organism survives:
○
Improper chromosome segregation --> diploid gametes
•
Recall: Meiosis
Autopolyploidy -two chromosome sets derived from one
species
•
Allopolyploidy -two chromosome sets derived from different
species (tabacco)
•
Changes in Ploidy Level
Surfeit of males (75%)
○
Sex determination makes duplication less viable
•
It is much more common in plants (up to 30-80% are
polyploidy)
•
Polyploidy events are rare in animals
308 chromosomes
•
Docosaploid -22n (black mulberry)
Heterosis -increase in performance (like hybrid virility)1.
Gene Redundancy -mask deleterious alleles; tolerant of
inbreeding
2.
Asexual reproduction possible3.
Benefits of Polyploidy:
*all these traits make for excellent founder species
Susumu Ohna (1970)
•
Evolutionary complexity is mediated by polyploidy
•
1R and 2R whole genome duplications -
500-900mya
!
This occurred twice in the common ancestor of all
vertebrates
○
Third round of duplication occurred in teleost fish
lineage (300mya)
○
Whole genome duplication (WGD) in vertebrates:
•
Time when gene sequences diverged
○
Transpositions
○
Segmental duplications -part of a chromosome
○
Tandem duplications -single genes or small DNA
regions
○
Phylogenetic interference for duplicated gene origins:
•
Different duplicate gene pairs originated around the
same time (~350mya) -date duplication through
phylogenetic analyses
○
Synteny segments of human genes on two different
tetraodon chromosomes
○
Proposed model for the distribution of ancestral
chromosome segments in the human and
tetraodon genomes
!
The composition of tetraodon chromosomes is
based on their duplication pattern whereas the
composition of human chromosomes is based on
the distribution of orthologues of tetraodon genes
!
*see slide
○
Evidence of teleost 3R WGD:
•
WGD -sudden doubling of every chromosome caused a
drastic change to the genome
○
Diploidization -the major evolutionary process
following WGD
○
Evolution after WGD:
•
Pseudogenes -genes that mutate and lose function
○
Subfunctionalization -partitioning of ancestral gene
functions among the duplicates
○
Neofunctionalization -one of the duplicates acquires a
novel functino
○
4 way recombination at meiosis
○
Like pairs with like
!
Neat and tidy process
!
In a diploid genome:
○
Too much similarity for neat and tidy process
!
Sometimes like pairs with like
!
Sometimes like pairs with 'almost like'
!
In tetraploid genome:
○
Evolutionary Consequences of WGD:
•
Evolution by Gene Duplication
Chromosomes come in different shapes and sizes
•
Acrocentric -at end
○
Metacentric -in middle
○
Fused acrocentric -end of one chromosome when fused
with another
○
Centromere is the tightly wound portion where spindle fibers
bind to pull pairs apart
•
Two metacentric homologues --> bivalent ring
○
Four metacentric homologues -->tetravalent ring
○
Traditional pairings:
•
A -normal chromosome pairing of 2 metacentrics
(bivalent ring)
○
B -normal pairing of 2 acrocentrics (bivalent rod)
○
C -4 way pairing with 2 acrocentrics and 2
metacentrics (multivalent rod)
○
D -4 way pairing of 4 metacentrics (multivalent ring)
○
*see viewing mitosis in a salmonid:
•
Quick Review: Chromosome Types
Evolution following 1R, 2R and 3R WGD proceeded to the
point where the chromosomes behave as two diploid pairs (no
4 way recombination at meiosis)
•
Contain a 4th WGD
○
'in between stage' of genome evolution
○
Pseudotetraploid -4 way recombination does happen
but is uneven
○
Faster in some places, slower in others
!
Evolution back to diploid state appears uneven
○
4 way recombination -large chromosome is a
prerequsite
○
Does the structure of the genome affect which regions
evolve back to diploid the fastest?
○
Salmonid specific whole genome duplication:
•
Chromosome structure and diploidization:
Homology -shared ancestry in DNA sequence
○
Homeology -chromosomes with shared ancestry within
species (result of duplication)
○
Comparison of DNA sequence within and across species:
•
Advances in WGD study:
Algorithm to find regions of similarity between sequences
(DNA, RNA and protein variants)
•
Lets researchers determine probability that two sequences
evolved from a common ancestor
•
Salmonids on Basic Local Alignment Search Tool (BLAST)
More acrocentrics than other salmonids (~28 pairs)
•
More ancestral karyotype than other salmonids
•
Arctic Char Karyotype:
Question: Does the structure of the genome affect which
regions evolve back to diploid the fastest?
•
Hypothesis: chromosome structure and 4-way recombination
causes the rate of diploidization to vary across the genome
•
Duplicate markers will be found near the telomeres of
chromosomes in higher frequency
1.
Duplicates will be found less on acrocentric homeolog
pairs
2.
Predictions:
•
4508 arctic char linkage map markers
○
1130 duplicate markers
○
Arctic Char Linkage Map:
•
Telomeres are the slowest diploidizing regions
○
Within chromosomes, more duplicate loci are preserved at
telomeres
•
No 4 way recombination
○
Diverge faster
○
Significantly lower numbers of duplicates markers on
acrocentric sets
•
More exchange
○
Within chromosomes, more duplicate loci preserved at
telomeres
•
Salmonid Diploidization:
Genome duplication allows for large scale evolutionary
changes
•
'back up copy' of every gene alleviates selection against new
mutations
•
Evolution after whole genome duplication is a messy process
•
Conclusions:
Genome Duplication & Subsequent
Evolution in Vertebrates
Friday,)September) 22,)2017 12:21)PM
Document Summary
Reduces chromosome number by half (--> sperm and eggs) Most of the time aneuploidy leads to death. If the organism does survive, they are usually sterile. In extremely rare circumstances, the mutant can survive and reproduce. Autopolyploidy - two chromosome sets derived from one species. Allopolyploidy - two chromosome sets derived from different species (tabacco) It is much more common in plants (up to 30-80% are polyploidy) Heterosis - increase in performance (like hybrid virility) Gene redundancy - mask deleterious alleles; tolerant of inbreeding. *all these traits make for excellent founder species. This occurred twice in the common ancestor of all vertebrates. Third round of duplication occurred in teleost fish lineage (300mya) Tandem duplications - single genes or small dna regions. Different duplicate gene pairs originated around the same time (~350mya) - date duplication through phylogenetic analyses. Synteny segments of human genes on two different tetraodon chromosomes.
