Chromosomal duplications

A chromosomal segment gets doubled in duplication mutation. The duplication mutation occurs in different segments of the chromosomes. Duplication mutations follow tandem configuration. It involves duplication mutation in chromosomal segments adjacent to each other. If the order of the duplicated segment is opposite to that of the original one, this kind of mutation is known as reverse tandem duplication. The terminal tandem duplication involves the arrangement of the duplicated segment in tandem at the end of the chromosome. A duplicated segment of chromosome exactly orients itself the same way as that of the normal region. Unequal crossing over leads to duplication of the chromosomal regions. The duplication rate reduces the survival rate of an organism.  

Tandem duplications lead to mispairing and unequal crossing over. The result of the crossover consists of two products having a tandem duplicated region, a product with a single copy of duplication, and another product with the triplicated regions. The heterochromatic regions undergo a special type of pairing known as a non-specific pairing or heterochromatic fusion. It leads to unequal crossing over. Another reason for the occurrence of the duplications involves primary structural changes in the chromosomes due to certain mutations, deletions, or other deficiencies. Crossing over in the inversion heterozygotes and translocation heterozygotes also produce duplications. The small-scale duplications (SSDs) involve duplicated stretches of DNA consisting of few genes. Large-scale duplications (LSDs) give rise to duplication of the entire chromosome. Whole genome duplication and polyploidy also arise due to large-scale duplications. Interspecific hybridization and chromosome doubling lead to aneuploids and polyploids. Non-disjunction of chromosome pairs causing the polyploid formation occurs either in the mitosis or meiosis.

Image: Types of duplication mutation

The role of gene duplications in the evolution:

Gene duplication played a crucial role in creating a new copy of a gene from a redundant old gene copy. Not all gene duplications prove to be useless or lethal. Some of the gene duplications also prove to be advantageous. For example, some of the hypotheses state that gene duplications led to evolution and species diversity. Gene duplications act as buffering agents acting against the null mutations. The retention of the duplicates is due to the buffering of the crucial genes. Gene duplication also helps in increasing the expression of products required in large amounts. For example, ribosomal proteins are required in large quantities in the cell for carrying out the process of translation. Similarly, the histone proteins are essential for the structural build-up of the chromosomes (DNA-histone complexes).

An important example of multigene families evolving through duplications includes globin genes. An important blood component known as hemoglobin consists of heme and four globin chains (two alpha globin chains and two beta-globin chains). It has an oxygen binding capacity. The genes encoding both the chains are present on two different chromosomes in the form of clusters with similar sequences. These sequences evolved from an ancestral gene through duplication. They mainly involved tandem gene duplications. Tandem gene duplication involves the duplication of both the regulatory sequences and exonic sequences. The alpha and beta globin genes in humans such as HBA1 and HBA2 encode identical products. Duplications also give rise to pseudogenes. Other important proteins such as cytoglobin, myoglobin, and neuroglobin also evolved due to the tandem duplications.

Chromosomal duplication also led to the evolution of the plant genome. Polyploidy is very common in the plants. The plant genetic maps based on low copy number markers help in inferring the chromosomal duplications.

Following are the examples involving duplications:

·        Bar mutants in Drosophila:

Tandem duplication produces bar-shaped eyes in Drosophila. Studies report the relationship between the Bar mutant on the X chromosome and reduced eye-size phenotype. Bar mutants arise due to the duplication of region 16A on the X-chromosome. Thomas Morgan and Alfred Sturtevant studied bar mutants in Drosophila for the first time. The homozygous bar mutants have less number of facets. A bar mutant arises due to less than a normal number of facets in the compound eye. Bar eye looks like a slit-shaped structure. The normal eye looks like an oval-shaped structure. The heterozygotes with bar mutations show a large number of facets. Heterozygous females with bar eyes are very common in Drosophila species.

·        Human red-green color blindness:

Color blindness or color vision deficiency arises due to X-linked recessive inheritance. The affected males pass on the trait to all the daughters who become carriers. The sons remain unaffected. The carriers daughters pass on the trait to the next generation having 50% affected sons and 50% carrier daughters. Unequal crossing over involving certain gene duplications constitute the main reason behind the red-green color blindness. Cone cells consist of pigments imparting a vision. These pigments are light-sensitive proteins playing an important role in ophthalmics. They impart color vision to the humans. A pigment known as rhodopsin imparts vision in the dim light. It is present in the rod cells. The cone pigments impart light sensitivities. They include blue, red and green colors.

The secret of human vision lies in perceiving the mixture of these three colors. The genes encoding the red and the green pigments are present on the X chromosomes (Xq28 position). Here comes the role of gene duplication. A single ancestral pigment gene gave rise to red and green pigment encoding genes. They arose due to subsequent gene duplications. Hence, they are similar in their amino acid sequences (96% identical). The genetic basis of red-green color vision deficiency arises due to an unequal crossing over between these two genes due to sequence similarity. An unequal crossing over between the homologous regions in the red and the green pigment genes results in two products. One product consists of a duplicated green pigment gene. The other product consists of deleted green pigment gene.

Protanopia refers to the inability to perceive red color. Protanomaly refers to an impaired ability to perceive red color. Impaired green color perception leads to deuteranopia and deuteranomaly. Males with a deleted green pigment gene on the X chromosome result in deuteranopia or green color vision deficiency. A crossing over between mismatched gene segments of both the colors results in a chimeric gene. It involves joining of a part of the green pigment gene with the part of the red pigment gene. When the 5’ end of the green pigment gene combines with the 3’ end of the red pigment gene to form a chimera, the crossing over point occurs in either of the two places. The crossing over point occurring near the 5’ end leads to a chimeric gene expressing red pigment. Hence, it leads to green blindness or deuteranopia. If the crossover point occurs near the 3’ end, the green pigment gene predominates. Hence, it leads to deuteranomaly. Consider another case of color vision deficiency. A chimeric gene consists of a red pigment gene at 5’ end and green pigment gene at 3’ end. Also consider two cases of unequal crossing over. If the crossover point is near the 5’ end, the green pigment gene predominates. The red pigment gene does not remain. Hence, it leads to red-blindness. If the crossover point is near the 3’ end, it results in protanomaly.

·        CNVs in autism and schizophrenia:

The human genome consists of a huge number of repetitive DNA sequences. Pairing between the repetitive sequences sometimes leads to ectopic recombination leading to chromosomal abnormalities. Gene copy number variation arises due to unequal crossing over. The autism spectrum disorders and schizophrenia show CNVs having repeated sequences showing duplications in some regions and deletions in other regions. 

References:

[1] Chromosome Structure and Aberrations, by Tariq Ahmad Bhat, Aijaz Ahmad Wani.
[2] Thompson & Thompson Genetics in Medicine, Robert L. Nussbaum, Roderick R. McInnes.
[3] Genetics, Daniel Hartl, Maryellen Ruvolo

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