Concerted Evolution Dan Graur
Divergent (classical) evolution vs. concerted evolution Expected Observed Ganley AR, Kobayashi T. 2007. Genome Res. 17:184-191.
Ribosomal RNA gene unit (in a cluster) ITS = internally transcribed sequences ETS = externally transcribed sequences NTS = nontranscribed sequences
Xenopus borealis Xenopus laevis
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.
(a) Stringent selection. (b) Recent multiplication. (c) Concerted evolution.
(a) Stringent selection. Refuted by the fact that the NTS regions are as conserved as the functional rRNA sequences.
(b) Recent multiplication. Refuted by the fact that the intraspecific homogeneity does not decrease with evolutionary time.
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.
CONCERTED EVOLUTION Concerted evolution results in a homogenized set of nonallelic homologous sequences.
CONCERTED EVOLUTION REQUIRES: (1) the horizontal transfer of mutations among the family members (homogenization). (2) the spread of mutations in the population (fixation).
Mechanisms of concerted evolution 1. Gene conversion 2. Unequal crossing-over 3. Duplicative transposition. 4. Gene birth and death.
gene conversion concerted evolution
Gene Conversion Unbiased Gene Conversion: Sequence A has as much chance of converting sequence B as sequence B has of converting sequence A. Biased Gene Conversion: 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 said to the master and the other to be the slave.
Gene conversion has been found in allspecies and at allloci that were examined in detail. Biased gene conversion is more common than unbiased gene conversion. The rate of gene conversion varies with genomic location.
unequal crossing-over concerted evolution
Unequalcrossing over Unequal crossing over
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.
following unequal crossing-over mild a-thalassemia
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.
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.
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.
concerted evolution: Advantages of Unequal Crossing-Over over Gene Conversion 2. In a gene-conversion event, only a small region is involved.
In yeast, an unequal crossing-over event involves on average ~20,000 bp. A gene-conversion track cannot exceed 1,500 bp.
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
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.
Types of arrangement of repeated units: • Dispersed • Clustered
The dispersed arrangement causes unequal crossing-over to lead to disastrous genetic consequences. The dispersed arrangement reduces the frequency of gene conversion.
3. relative sizes of slowly and rapidly evolving regions within the repeat unit.
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.
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
Selection against variation Selection against homogeneity 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
Concerted evolution under unequal crossing-over is quicker than that under gene conversion.
The time required for a variant to become fixed in a population depends on population size.