The Beauty of Mutations

What kinds of errors can occur in DNA?
What causes them?
What are their effects?

Types of mutations

Chromosomal Mutations

Mutations can occur at a fairly macroscopic level. Large sections of chromosomes can be altered or shifted, leading to changes in the way the genes on them are expressed.

Translocations involve the interchange of large segments of DNA between two different chromosomes. This can change expression of genes if a gene is at the translocation breakpoint or if it finds itself reattached ina way that it is regulated by a new promoter region, which is not tailored to its expression needs.
Inversions occur when a region of DNA flips its orientatio nwith respect to the rest of the chromosome. This can lead to the same problems as translocations.
Sometimes large regions fo a chromosome are deleted. This can lead to a loss of important genes.
Sometimes chromosomes can lose track of where they are supposed to go in cell division . One of the daughter cells will end up with more or less than its share of DNA. This is called a chromosome nondisjunction.

The more important problem with chromosomal rearrangements, however, is not that the genes at the breakpoint of rearrangement are damaged. When large regions of a chromosome are altered, it may lose the ability to segregate properly during cell division, causing a chromosomal nondisjunction. When a new cell gets less or more than its share of DNA, it will have problems with gene dosage. Expression of genes is specifically tailored to z level that a cell requires. When there are extra or too few copies of the gene, the cell runs into trouble.

Point Mutations

Point mutations are single base pair changes. What effect does that have on the encoded protein?

A nonsense mutation creates a stop codon where none previously existed. This shortens the resulting protein, possibly removing essential regions.
A missense mutation changes the code of the mRNA. If an AGU is changed to an AGA, the protein will have an arginine where a serine was meant to go. This might alter the shape or properties of the protein.
A silent mutation has no effect on protein sequence. If an AGU was changed to an AGC, the protein would still have the appropriate serine at that position.

Within a gene, small deletions or insertions of a number of bases not divisible by 3 will result in a frame shift. For example, given the coding sequence:

AGA UCG ACG UUA AGC

corresponding to the protein

arginine - serine - threonine - leucine - serine

The insertion of a C-G base pair between bases 6 and 7 would result in the following new code, which would result in a non-functional protein. Every amino acid after the insertion will be wrong.

AGA UCG CAC GUU AAG C

arginine - serine - histidine - valine - lysine

The frame shift might even generate a stop codon which would prematurely end the protein.

DNA Repair

If replication of DNA proceeded as was described previously, the DNA polymerase wouold make a mistake on average about every 1000 base pairs. This level would be unacceptable, because too many genes would be rendered non-functional. Organisms have elaborate DNA proofreading and repair mechanisms, which can recognize false base-pairing and DNA damage, and repair it. The actual error rate is more in the region of one in a million to one in a billion.

So Why Are Mutations Beautiful?

Our environment is constantly changes, as the dynamic Earth and its ecosystems change. We must change along with it, or we will become obsolete and die. One mechanism of change is at the DNA level. Mutations can often result in beneficial new genes and functions, which enable and organism to adapt to a changing environment.

However, most mutations are deleterious, and cause many of the genetic diseases that we are discovering today.

hyperbio@mit.edu