Download Gene Duplication and Gene Families

Gene Duplication and Gene Families
Reading MGAe2
Duplications
p. 372 (ignore 2nd paragraph); Fig 11-19b
Duplications
p. 634-635
Gene Duplications
Duplications may be "tandem" or "insertional" (non-tandem).
The most likely scenario for tandem gene duplication is "unequal crossing over".
Gene Duplication and Deletion by Unequal Crossing Over
Meiotic Pairing In Duplication Heterozygote
Tandemly repeated sequences facilitate unequal crossing over leading to expansion/contraction of the
tandem array. The relatively high frequency of unequal crossing over is responsible for the
hypervariability of VNTR, minisatellite, and microsatellite sequences.
Meiotic Pairing In Duplication Homozygote.
Amplification of duplication by unequal crossing over within "asymmetric
pairing" region
Gene duplication may lead to altered phenotypic expression due to change in relative gene dosage
(imbalance).
Natural selection on a duplicated copy may be relaxed, allowing it to accumulate mutations and either
evolve modified functions or degenerate into a non-expressed pseudogene.
Gene Families (Gene Clusters, Tandem Gene Arrays)
A gene family is a set of genes created by duplication of an ancestral gene.
Genes in a family may occur in tightly linked tandem arrays, or be dispersed on different chromosomes
(following translocation events).
Duplicated copies of genes in gene families may be
freed from the constraints of natural selection and allowed to accumulate mutational changes without
phenotypic effect. They may evolve modified, or more rarely, completely different functions. Even when
genes in a family have similar functions they may be expressed in different tissues and at different times
of development. Alternatively, and this may be more common, duplicated genes may degenerate into
non-functional pseudogenes.
In other gene families, all copies of the gene have essentially identical sequence and function. Such gene
families always exhibit tight linkage of all genes in the family. The products of genes in such families are
frequently required in large amounts.
When the sequences of all genes in a family are identical, it does not mean that the shared sequence is
identical to the sequence of the original gene, but that all sequences in the array are subject to concerted
evolution and homogenization. The maintenance of such clusters of identical genes demands a
mechanism to homogenize their sequences and prevent divergence by accumulation of incremental
changes. Such mutations would be only weakly opposed by selection.
Unequal crossing over is one possible mechanism to homogenize genes in a family. In the model shown
to the right, abcde represent a tandem array of five repeats that, while they have diverged in sequence,
still retain sufficient homology to exhibit asymmetric pairing. The scenario envisions expansion of b by
unequal crossing over, leading to displacement of the other sequences.
Examples
Gene Family
#Genes
animal globin proteins
2-50
modified gene function/dispersed
opsins (visual pigment proteins) 4-?
mammalian lysozyme/lactalbumin
rRNA
histones
conserved function
100-1,000
Immunoglobul;ins
Actins
5-30
>500
modified gene function/dispersed
novel function
Thalassemia
The thalassemias are a group of genetic defects with variable clinical manifestations due to
derangements of hemoglobin production. The thalassemic conditions are associated with inheritance of
chromosomes that lack one or more normal globin genes. In some thalassemias the aberrant
chromosome contains a chimeric globin gene (such as "Lepore") that must have arisen by unequal
crossing over.
Draw a diagram of
meiotic pairing between two normal copies of chromosome 11 to show how unequal crossing
over could produce the Lepore globin gene.
Lactalbumin
The mammalian α-lactalbumin gene arose by duplication of the lysozyme gene, and subsequently
evolved an entirely new function, although its regulation has apparently not changed.