Question

How do mutations occur and how can environmental factors increase mutation rates?

How do mutations affect proteins and their expression?

Does the location of the mutation within a gene matter to phenotype expresion, if so, how?

How do mutations affect phenotypes?

Can we predict the impact of a mutation on protein activity?

What are loss-of-function and gain-of-function mutations?

Answer 1

Q ) Mutation is a permanent alteration of nucleotide sequence of a genome.it causes changes in genetic make up of an organism. The changes can be at the gene level called gene mutation or point mutation or change in chromosome structure or number called chromosomal mutation.

How mutation occurs -

Mutations occurs due to error at the time of DNA replication or other types of damage to DNA (like exposure to radiation or carcinogens). After this it undergoes an error-prone repair, or cause an error during other forms of repair. Mutations may also occur due to insertion or deletion of segments of DNA due to mobile genetic elements.

The substances which causes mutation are called mutagens, They cause permanent change of the physical composition of a DNA, Due to this the genetic message also changes. Once the gene is damaged or changed, the mRNA transcribed from that gene will carry an altered message.These mutagens may be chemical or environmental.

How can environmental factor increase mutation rate-

Mutation can be caused by environmental factors like ultraviolet ray from sun.Sunlight contains ultraviolet radiation when it is absorbed by nucleic acids it causes alteration in bond character of purines and pyrimidines, the bases altered are known as photoproducts. Pyrimidines are more prone to such changes, two adjascent pyrimidines of same DNA strand form covalent bonds forming dimers. Mostly thymine dimer is formed easily. Dimerization interferes with the proper base pairing of thymine with adenine and causes pairing of thymine with guanine. This substitutes T A to CUG . Similarly cytosine dimer causes mutations by becoming deaminated to uracil dimers and produce G C to AT transition, as a result mutation rate increases.
Unprotected exposure to UV radiation by the human skin can causes serious damage at the genetic level and may lead to skin cancer due to mutation.

How do mutations affect proteins and their expression?-

Some DNA mutations are silent and have no effect, but some other mutations affect proteins and their synthesis.  A mutation is a change in a DNA sequence occuring due to a mistake done at the time of copying of DNA. Mutation also occures due to damage by chemicals. In DNA genes, gives instructions for synthesis of protein molecules, when they are altered the synthesis and expression of proteins gets affected.

In other words according to defination of central dogma - DNA makes RNA and RNA makes protein. So the code in DNA determines the code in mRNA, and the code in mRNA determines the sequence of amino acids. The amino acid chains are the basis of protein structure. So, when something goes wrong in DNA, mRNA will also be affected. If the mRNA is wrong, then the amino acid chain produced will be wrong. And it will cause a problem in the protein.

What are loss of function and gain of function mutation-

A type of mutation in which the altered gene product possesses a new molecular function or a new pattern of gene expression. Gain-of-function mutations are almost always Dominant or Semidominant.

Loss-of-function mutation is a mutation that results a reduced or abolished protein function.