Duplications of DNA sequences are a fundamental feature of genome evolution.

Types of sequence duplications

• Partial gene duplication
  • Duplication of exons
  • Internal duplication to expand a gene
  • Duplication of an exon and a subsequent "donation" to another gene (exon shuffling)

• Complete Gene duplication

• Partial or complete chromosome duplication
  • Generally rare events as aneuploid gametes are usually bad news

• Polyploid -- whole genome duplication
  • Very common in plants (many crop species are polyploids)

    Autopolyploids

    Self-polyploids

    Multiple chromosome sets from the same parent

    Allopolyploids

    Chromosome sets from different parents

• E. coli chromosome shows evidence of a genome duplication

• Yeast also shows a recent chromosome doubling

• On-going debate as to whether tetrapods (four-limbed vertebrates) underwent two genome duplications (i.e., the tetrapod genome is a teraploid of the ancestral mammalian genome)

Orthologous vs. Paralogous Comparison of Duplicates

When comparing two related duplicate genes in different species, there are two types of comparisons:

• Orthologous comparisons --- the two copies are derived from a speciation event (alpha hemoglobin in mice and humans)

• Paralogous comparison --- the two copies are be traced back to a duplication event (alpha Hb in mice vs. beta Hb in humans). Under a paralogous comparison, the common ancestor of the two copies being compared is much deeper than the speciation event.

Fates of a Recently Duplicated Gene

Pseudogenes

• The duplication process itself may produce a defective copy

• A striking example are Processed pseudogenes. Here an mRNA is reversed-transcribed into a cDNA copy that is inserted back into the genome. Signals of this
  • Poly-A tail
  • Introns removed
  • only the transcript is copied (hence, the promoter and other regulatory elements are missing)

• Alternatively, a completely functional duplication may occur and become fixed in the population (say by drift). Subsequently one of the copies may fix an inactivating mutation
  • This can change linkage relationships (Haldane 1935)

Neofunctionalization

One of the duplications may acquire a mutation (most likely regulatory) that gives it a slightly different function from the original. This is neofunctionalization of one of the copies, and selection will thus retain both copies.

Subfunctionalization

If the original copy carried out several independent functions (say it has two independent promoters for two different tissues), then the appropriate null mutations may knock out one function but keep the other. If the appropriate mutations occur, the original function may be partitioned over both copies so that both are now needed to carry out the original function and hence selection retains both copies.

Families and Superfamilies of Genes

Structural Organization of Gene Family Members

Gene family members can occur as a linked Gene Cluster or set of clusters.

The most extreme example of a cluster is a tandem array, with all copies arrayed head-to-tail. rRNA genes are typically arrayed in this fashion.

Alternatively, copies can be dispersed throughout the genome

• Oprons -- are genes of a family that are unlinked to any other family members (they have "lost" their families).

Types of Repeated genes

• Invariant repeats. Examples are histones and rRNA genes. Need a large amount of product, often in a short period of time.
  • Invariant repeats often occur in tandem arrays.

• Variant repeats -- variants of the same general theme with slightly different functions.

  Example: Globin gene superfamily

Concerted Evolution of Gene Family Members

Observation of Concerted Evolution

Many gene families show a most interesting behavior, first observed in the NTS spacer regions of the rRNA gene in the frog Xenopus.

Why is this observation unusual? If each gene evolved independently, we would expect orthologou comparisons to show a higher level of sequence similar than s paralogous comparisons among family members within the same species.

Hence, Genes in the family appear to have evolved together as a group, rather than independently.

Key: Gene family members within a species seem to have shared a common ancestral sequence following the speciation event.

Mechanisms of Conserved Evolution

What mechanisms can account for this observation?

Unequal crossing

Recombination between homologous sequences in a tandem array

Unequal crossover changes the number of copies. Repeated cycles of unequal crossingover results in all copies descending from a single ancestral copy,

For n genes, it takes roughly n² crossover events to homogenize the family. If the rate of unequal crossingover is c per generations, then it takes roughly n²/c generation to homogenize the family.

Gene Conversion

DNA sequences showing some level of sequence similar can undergo gene conversion, the non-reciprocal transfer of sequence information.

Unlike unequal crossingover, this does not require that genes are linked nor does it change copy number. Again, it takes roughly n²/c generation to homogenize the family.

Gene conversion common occurs between different genes. In fact, in yeast it is involved in switching the mating type of a cell.

Finally, gene conversion can potentially show bias, with one seuqence being more favorabily converted over others. This can impart a directional force on the evolution of the gene family.

Homogenization of a gene family be either gene conversion or unequal crossingover is akin to genetic drift homogenizing all the alleles within a finite population.

Birth and Death Models for Concerted Evolution

If gene families under expansion (through gene amplification) following a speciation event, then the family members within a species are more closely related than family members between species.

Evolutionary Implications

As mentioned, if there is no selection to maintain sequence identify among family members, then the above forces at the molecular level (conversion, unequal crossingover) act akin to drift. Like drift, their actions can be opposed by the effects of selection.

Indeed, very weak selection can easily prevent concerted evolution from occurring.

A briefly popular notion in the early 1980's was Gabby Dover's idea of "Molecular drive", wherein these molecular forces acting on gene families overpowered selection and drove evolution. The population genetic models are not consistent with this view.

Indeed, concerted evolution can actually make selection more efficient, as unequal crossingover or conversion spreads a favorable mutation across family members, as opposed to having to wait for each member to independent acquire the same favorable mutation.

Likewise, by spreading an unfavorable mutation across family members, the forces of concerted evolution likewise enhance the efficiently of selection. These forces increase the variation in fitness among different individuals, which increases the efficiency of selection in removed a weakly deleterious allele.