Concerted Evolution

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Concerted Evolution
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Divergent (classical) evolution vs. concerted
evolution
Ganley A. R., Kobayashi T. Genome Res.
200717184-191
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Ribosomal RNA gene unit (in a cluster)
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Xenopus borealis
Xenopus laevis
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18S and 28S in X. laevis and X. borealis are
identical. NTS regions differ between the two
species. NTS regions are identical within each
species. Conclusion NTS regions in each
species have evolved in concert, but have
diverged rapidly between species.
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(a) Stringent selection. (b) Recent
multiplication. (c) Concerted evolution.
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(a) Stringent selection. Refuted by the fact
that the NTS regions are as conserved as the
functional rRNA sequences.
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(b) Recent multiplication. Refuted by the fact
that the intraspecific homogeneity does not
decrease with evolutionary time.
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(c) Concerted evolution.
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CONCERTED EVOLUTION A member of a gene family
does not evolve independently of the other
members of the family. It exchanges sequence
information with other members reciprocally or
nonreciprocally. Through genetic interactions
among its members, a multigene family evolves in
concert as a unit.
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CONCERTED EVOLUTION Concerted evolution results
in a homogenized set of nonallelic homologous
sequences.
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CONCERTED EVOLUTION REQUIRES (1) the horizontal
transfer of mutations among the family members
(homogenization). (2) the spread of mutations in
the population (fixation).
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Mechanisms of concerted evolution 1. Gene
conversion 2. Unequal crossing-over 3.
Duplicative transposition.
Later
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gene conversion ? concerted evolution
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Gene Conversion Unbiased Sequence A has as
much chance of converting sequence B as sequence
B has of converting sequence A. Biased The
probabilities of gene conversion between two
sequences in the two possible directions occur
are unequal. If the conversional advantage of
one sequence over the other is absolute, then one
sequence is the master and the other is the slave.
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Gene conversion has been found in all species and
at all loci that were examined in detail.
Biased gene conversion is more common than
unbiased gene conversion. The rate of gene
conversion varies with genomic location.
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unequal crossing-over ? concerted evolution
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Unequal crossing over
Unequal crossing over
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Tomoko Ohta
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concerted evolution Advantages of Gene
Conversion over Unequal Crossing-Over 1. Unequal
crossing-over changes the number of repeats, and
may cause a dosage imbalance. Gene conversion
does not change repeat number.
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normal configuration
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following unequal crossing-over
mild a-thalassemia
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concerted evolution Advantages of Gene
Conversion over Unequal Crossing-Over 2. Gene
conversion can act on dispersed repeats. Unequal
crossing-over is severely restricted when repeats
are dispersed.
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deletion
duplication
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concerted evolution Advantages of Gene
Conversion over Unequal Crossing-Over 3. Gene
conversion can be biased. Even a small bias can
have a large effect on the probability of
fixation of repeated mutants.
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concerted evolution Advantages of Unequal
Crossing-Over over Gene Conversion 1. Unequal
crossing-over is faster and more efficient in
bringing about concerted evolution.
At the mutation level, UCO occurs more frequently
than GC.
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concerted evolution Advantages of Unequal
Crossing-Over over Gene Conversion 2. In a
gene-conversion event, only a small region is
involved.
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In yeast, an unequal crossing-over event involves
on average 20,000 bp. A gene-conversion track
cannot exceed 1,500 bp.
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Factors affecting the rate of concerted
evolution 1. the number of repeats. 2. the
arrangement of the repeats. 3. relative sizes of
slowly and rapidly evolving regions within the
repeat unit. 4. constraints on homogeneity. 5.
mechanisms of concerted evolution. 6. population
size. 7. dose requirements
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1. the number of repeats.
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The number of unequal crossing-overs required for
the fixation of a variant repeat increases
roughly with n2, where n is the number of
repeats.
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2. the arrangement of the repeats.
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Types of arrangement of repeated
units Dispersed Clustered
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The dispersed arrangement causes unequal
crossing-over to lead to disastrous genetic
consequences. The dispersed arrangement reduces
the frequency of gene conversion.
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3. relative sizes of slowly and rapidly evolving
regions within the repeat unit.
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Noncoding regions evolve rapidly. Coding
regions evolve slowly. Both unequal
crossing-over and gene conversion depend on
sequence similarity for the misalignment of
repeats. The more coding regions there are, the
higher the rates concerted evolution will be.
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4. constraints on homogeneity.
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Two extreme possibilities 1. The function
requires large amounts of an invariable gene
product. rRNA and histone genes 2. The
function requires a large amount of diversity.
immunoglobulin and histocompatibility genes
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5. mechanisms of concerted evolution.
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Concerted evolution under unequal crossing-over
is quicker than that under gene conversion.
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6. population size.
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The time required for a variant to become fixed
in a population depends on population size.
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7. dose requirements.
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Centripetal selection against too many or too few
repeats.
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2 loci, 3 alleles
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Detecting Concerted Evolution
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When dealing with similar paralogous sequences,
it is usually impossible to distinguish between
two alternatives (1) the sequences have only
recently diverged from one another by
duplication. (2) the sequences have evolved in
concert.
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The phylogenetic approach. The two a-globin
genes in humans are almost identical. They were
initially thought to have duplicated quite
recently, so there was no sufficient time for
them to diverge in sequence.
a1
a2
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The phylogenetic approach. However, duplicated
a-globin genes were also discovered in distantly
related species, so most parsimonious solution to
assume that the duplication is quite ancient, but
its antiquity is obscured by concerted evolution.
a1
a2
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g
duplication
55 million years ago
Gg
Ag
speciation
5 million years ago
The orthologs should be closer to one another
than the paralogs.
Gg
Ag
Gg
Ag
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In humans, the 5 parts of Gg and Ag differ from
one another at only 7 out of 1,550 nucleotide
positions (0.5). In contrast, the 3 parts of
Gg and Ag differ from one another at 145 out of
1,550 nucleotide positions (9.4).
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exon 3
exons 1 and 2
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exon 3
exons 1 and 2
Expected phylogenetic tree for exons 1 and 2, if
gene conversion had only occurred in the human
lineage.
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Death is not final The resurrection of
pancreatic ribonuclease as seminal ribonuclease
in Bovinae by gene conversion
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The resurrection of pancreatic ribonuclease as
seminal ribonuclease in Bovinae through
gene-conversion of a small region at the 5' end
of the gene.
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Pseudogenes may represent reservoirs of genetic
information that participate in the evolution of
new genes, not only relics of inactivated genes
whose fate is genomic extinction.
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21-hydroxylase (cytochrome P21) gene In humans,
the 10-exon gene is located on chromosome 6.
The gene has a paralogous pseudogene in the
vicinity.
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21-hydroxylase (cytochrome P21) gene Hundreds of
mutations in the 21-hydroxylase gene have been
described. 75 of them are due to gene
conversion.
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gene ATGTCTCTGACCAAGGCTGAGAGGACCATGGTC
GTGTCCATATGGGGCAA pseudogene
ATGTCTCTGACCAAGGCTGAGAGGACCATGGTCGTGTCCATATGGGGCAA

gene
GATCTCCATGCAGGCGGATGCCGTGGGCACCGAGGCCCTGCAGAGGTGAG
pseudogene GATCTCCATGCAGGCGGATGCCGTGGGCACCGA
GGCCCTGCAGAG-----

gene TGCCAGACAGCCTGGGACAGGTGACAGTGTCC
CAGGTGACACTGGTGTAG pseudogene
--------------------------------------------------

Gene
GTGACAGCGTGAGTTTAGTGAGGACAGGGGCCAGTGAAGAGGGGGCAATG
pseudogene ---------------------------------
-----------------
gene
AGGAAGCGACAGTGTGGAGGGGTAATTGTGGTGGGGAACTGTGAGGAC
CC... pseudogene ----------------------------
----------------------

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Were it not for the fact that the pseudogene is
truncated, we would be hard pressed to say which
is the gene and which is the pseudogene.
gene ATGTCTCTGACCAAGGCTGAGAGGACCATGGTC
GTGTCCATATGGGGCAA pseudogene
ATGTCTCTGACCAAGGCTGAGAGGACCATGGTCGTGTCCATATGGGGCAA

gene
GATCTCCATGCAGGCGGATGCCGTGGGCACCGAGGCCCTGCAGAGGTGAG
pseudogene GATCTCCATGCAGGCGGATGCCGTGGGCACCGA
GGCCCTGCAGAG-----

gene TGCCAGACAGCCTGGGACAGGTGACAGTGTCC
CAGGTGACACTGGTGTAG pseudogene
--------------------------------------------------

Gene
GTGACAGCGTGAGTTTAGTGAGGACAGGGGCCAGTGAAGAGGGGGCAATG
pseudogene ---------------------------------
-----------------
gene
AGGAAGCGACAGTGTGGAGGGGTAATTGTGGTGGGGAACTGTGAGGAC
CC... pseudogene ----------------------------
----------------------