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Life Sciences => Cells, Microbes & Viruses => Topic started by: Ripu Daman Singh on 08/07/2009 12:30:04

Title: How do mutations of more than one base change arise?
Post by: Ripu Daman Singh on 08/07/2009 12:30:04
Ripu Daman Singh  asked the Naked Scientists:
   
Chris,

Love your show (http://www.thenakedscientists.com/HTML/podcasts/)!  By far the best podcast (http://www.thenakedscientists.com/HTML/podcasts/).

I read a bbc report with the following content:
"... These mutations - where one letter of the DNA code is substituted for another - are a first step in evolution.

DNA can mutate and change imperceptibly every time a cell divides and makes a copy of itself.
But when one of these mutations causes a change that is advantageous for the animal - for example, rendering it resistant to a particular disease - it is often "selected for", or passed down to the next few generations of that same species."

Questions:
1.  Can just one letter change in the DNA, in the right place, actually change behavior of the Gene in a significant and functional way?
2.  How do changes involving more than just one letter evolve?
3.  It will take many one letter changes for a Gene to Mutate from a sequence of AAGCTGAC to say AGAGCTAGACA .  Each of these one-letter changes will need to be functional sequences in order to survive in the species.  That means we can predict the path of mutation since any non-functional one letter change will obviously die out.  Is this true?  Do we use this information today?  If yes, how?

Regards,
-rds

What do you think?
Title: How do mutations of more than one base change arise?
Post by: wolfekeeper on 16/07/2009 15:01:16
Generally only one mistake will happen at once, it could be a replacement, substitution or a section that gets swapped or duplicated or a virus could insert itself etc. etc.

The chances of a mistake being beneficial is low; the chances of the combination of two mistakes being beneficial when one isn't is far lower still; and if either one is beneficial on its own, that's much more likely to happen first, followed by the other.

So generally, most mutations have to be beneficial or not significantly detrimental pn their own to be selected.
Title: How do mutations of more than one base change arise?
Post by: Chelsie on 19/07/2009 21:34:54
1. Can just one letter change in the DNA, in the right place, actually change behavior of the Gene in a significant and functional way?

It can change the function of the protein synthesized via the gene, but it depends on whether the mutation is a conservative change or a non conservative change.

As you may already know, DNA or more specifically the singular genes within DNA are the blue prints for making proteins. After DNA is transcribed into RNA, the RNA bases are read in triplicates which code for amino acids. 3 bases in a specific order = 1 amino acid.

Example:
The triplicates CAC result in the amino acid Histidine.
The triplicates AGC result in the amino acid Serine.
The list goes on...
 
Each gene specifies how the amino acids will be sequenced. One full sequence of amino acids is called a polypeptide (AKA a single stranded protein). The sequence of amino acids specify how the single strand of protein will fold into it's final shape. The shape of the protein is extremely important because the shape determines it's function. The reason genetic diseases arise is because mutations cause the protein to fold incorrectly which renders it semi - completely dysfunctional. 

There are 20 amino acids. Each have different molecular properties. For example: Practically everything in a living organism comes in contact with water. The amino acid Leucine is very hydrophobic, meaning it hates water and will do whatever it can to stay out of water. On the other hand, the amino acid Serine is very Hydrophilic, meaning it loves water so it will do what it can to be in the water. Lets assume that a normal (non mutated) protein strand has many hrdrophobic amino acids in one area of it's strand and many hydrophilic amino acids in another area of it's strand. The hydrophobic region will do whatever it can to be away from the water so it folds inwards. The hydrophilic area will want to be in the water so it folds outwards. So, depending on the amino acid and where they are located on the protein strand determines how the protein will fold. There are many other factors involved in protein folding but it would take an extreme amount of explaining. I just wanted to give you a quick example!
 

The reason single base mutations can be damaging is because they can turn one amino acid into another. For example: if the mutation turns a hydrophilic amino acid into a hydrophobic amino acid, that amino acid will no longer want to be in the water and will cause the protein to fold differently. This is called a non conservative mutation and they can greatly impact the function of a protein leading to disease.

On the other hand, a single base mutation can be conservative and will not impact the way a protein folds. For example: if the mutation turns a hydrophobic amino acid into another hydrophobic amino acids, the protein folding will be less impacted and it will retain it's function.

Another fact to consider is that amino acids can be coded by more than one triplicate sequence. There can be a single base mutation but it may still code for the same amino acid.

2.  How do changes involving more than just one letter evolve?

I'm not quite sure what you're asking here. As you asking why multiple base mutations happen or how evolution works at the molecular level? If you can clarify, I will try my best to answer :) :)