Whole Genome Duplications (Polyploidy)
Made famous by S. Ohno, who suggested WGD can be a route to
evolutionary innovation (focusing on neofunctionalization)
Ohno proposed in the 1970s that vertebrate lineage underwent two WGDs
… later confirmed with whole-genome sequence data.
WGDs are most common in plants but observed in vertebrates, fishes, yeast,
and Paramecium, among other species
Major mechanisms of polyploidy
1. Gametic nonreduction - production of unreduced gametes
caused by an error in meiosis
2. Somatic doubling - production of a cell with twice the normal
chromosome number caused by an error in mitosis
3. Polyspermy – fertilization of multiple gametes
Errors in meiosis/mitosis can be caused by genetic or environmental factors
Production of 2n gametes
Spindle error or failure
Abnormal chromosome
pairing
Abnormal or absent
cytokinesis
Pre-meiotic doubling
Produced at an average
rate of 0.5% per gamete
Bretagnolle and Thompson New Phytol. (1995) 129: 1-22
Types of Polyploidy
Autopolyploidy – chromosomal
duplications derived from the same
species … produce ohnologs
Allopolyploidy – chromosomal
duplications derived from different species
… produce homeologs
Timeline after WGD
1. Initial duplication of entire genome
autopolyploid = identical genome
2. Gene loss is likely frequent immediately after (although some papers
find no evidence of this)
which copy is lost is initially random
2. As sequences diverge, loss may not be random
sub/neofunctionalization may favor retention of specific ohnologs
4. Chromosomal rearrangements reduces 2X chromosome number
5. Reciprocal Gene Loss (RGL) in different individuals
can promote speciation
From Kellis & Lander. Nature 2004
Reciprocal Gene Loss (RGL): differential loss of ohnologs can
lead to speciation (due to problems pairing chromosomes)
Ancient WGD’s correlate with increased species diversity and even radiations
Mating
WGD-driven speciation (via RGL) may be more likely to occur soon after WGD:
rate of gene loss is highest soon after WGD and
the copy lost isRGL
more
in likely to be random
individuals
WGD
event
Difficulties during
subsequent meiosis (F2s)
The costs & benefits of WGD
Costs:
Doubles the DNA content and chromosome number
More DNA = larger cells, larger volume, more proteins required
Benefits:
Doubles whole pathways of functionally related genes
Maintains balanced expression across the genome
The Balance Hypothesis
Single-gene duplication can = stoichiometric imbalance
WGD maintains stoichiometry (at least initially)
The Balance Hypothesis predicts
that proteins in multi-subunit complexes
and proteins that require precise
stoichiometry are more likely to be influenced
by WGD vs single-gene duplications
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
(“6 – 36% of ohno. pairs have one with higher rate of divergence
note this evolution can occur at the level of function OR expression
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
note this evolution can occur at the level of function OR expression
2. Buffering (?)
Observation: yeast genes with retained ohnologs have less phenotypic consequence
of deletion … probably due to redundancy
? But is the driving force for their retention?
( seems weird that buffering could drive their retention )
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
note this evolution can occur at the level of function OR expression
2. Buffering (?)
3. Benefit of copy number increase (maintaining stoichiometry across pathways)
e.g. Most glycolytic enzymes & most ribosomal proteins in S. cerevisiae
are retained Ohnologs
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
note this evolution can occur at the level of function OR expression
2. Buffering (?)
3. Benefit of copy number increase (maintaining stoichiometry across pathways)
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
note this evolution can occur at the level of function OR expression
2. Buffering (?)
3. Benefit of copy number increase (maintaining stoichiometry across pathways)
4. Need to maintain stoichiometry across pathways
The fate of duplicate genes after WGD
1. ‘Classical’ sub- or neo-functionalization
note this evolution can occur at the level of function OR expression
2. Buffering (?)
3. Benefit of copy number increase (maintaining stoichiometry across pathways)
4. Need to maintain stoichiometry across pathways
5. Evolution of new regulatory circuits (‘rewiring’)
Veron et al. Mol Biol Evol 2007
unicellular ciliate (eukaryote): evidence of three ancient and successive WGDs
-
find no evidence for rapid gene loss shortly after WGD
the latest WGD correlates with expansion of sister species
10-16% of ohnologs show asymetric evolutionary rates (i.e. one copy faster)
Gene retention driven by stiochiometric requirements (complexes) and expression
abundance (higher expression = more likely to be retained)