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Divergence in coding sequence of different functional categories of immune genes between species of the order Rodentia

Andersson, Samuel (2021) MOBK01 20211
Degree Projects in Molecular Biology
Popular Abstract
How mice avoid diseases, a measure of divergence

The response we have to diseases vary from person to person. In much the same way diseases affect and are battled in many different ways depending on the species. This happens due to differences in their immune system. So, what causes these differences? Well, they are mostly caused by differences in the DNA, the molecule which has the code for everything that makes you, you. This DNA in turn has a multitude of different genes which contain the code for just as many proteins. In different species these genes, and the DNA as a whole, may be similar, but it has enough of a difference to make up two different species.

This is where divergence comes in. Divergence is a measure of the... (More)
How mice avoid diseases, a measure of divergence

The response we have to diseases vary from person to person. In much the same way diseases affect and are battled in many different ways depending on the species. This happens due to differences in their immune system. So, what causes these differences? Well, they are mostly caused by differences in the DNA, the molecule which has the code for everything that makes you, you. This DNA in turn has a multitude of different genes which contain the code for just as many proteins. In different species these genes, and the DNA as a whole, may be similar, but it has enough of a difference to make up two different species.

This is where divergence comes in. Divergence is a measure of the difference between two closely related species. An example would be the animals that provided the DNA used in this study: mice and rats. These two have DNA and by extension genes that are closely related, something which is also known as orthologs. It is in orthologs where divergence is studied.

Divergence also measures natural selection in a gene. Depending on the value, we can tell whether changes in selected genes are positive, negative or does not affect the animal. What is it used for? In this project, I looked at differences between the genes in the immune system of 15 different rodent species with the goal being to find how much change these genes are allowed.

How was this done? By comparing the different rodent genes in a process called alignment. Alignment is a process in which two or more, in this case orthologs, are compared to find the best way they match up with each other. By then comparing them and finding where they are different, we can get a rough measure of divergence through three different variables, dN, dS and dN/dS. These can roughly be explained as dN being the amount the gene has changed, dS being the rate at which the gene changes and dN/dS being the mode and strength of natural selection described before. These values are then analysed to make sure that the values have not come about through coincidence. Additionally, these genes were categorised into 3 different categories; recognising proteins called PRRs, signal proteins called cytokines and a huge category where all other genes were placed.

So, what were the results of this study? I found that there was in fact no randomness to these numbers and that receptors and cytokines had a much higher dN, dS and dN/dS than the other genes. This meant that they had more changes between species, they seemingly mutated faster, and these changes were allowed to stay to a higher degree.

This meant that further analysing could be done. As such I also analysed whether there was change within the PRRs and cytokines depending on for example what they bound to or whether they were signals or receivers. Almost no change was found between these subgroups. This was a bit surprising as earlier work has found that there is change within in at least the PRR group.

So, what do we use these results for? It is well known that PRRs need to compete with rapidly evolving pathogens such as bacteria. Now that we know there is a similar amount of change between PRRs and cytokines we can ask why this is. Why would signals in the immune system need to change as much as the receptors recognising the rapidly evolving disease-causing pathogens? Some studies have found that certain pathogens mimic these cytokines to diminish the immune response towards them. This could potentially be an explanation. This could shed some light into how pathogens evade our own immune system.

Supervisor: Lars Råberg
Assistant supervisor: Mridula Nandakumar
Examensarbete 15 hp i molekylärbiologi 2020
Biologiska institutionen, Lunds universitet (Less)
Please use this url to cite or link to this publication:
author
Andersson, Samuel
supervisor
organization
course
MOBK01 20211
year
type
M2 - Bachelor Degree
subject
language
English
id
9064144
date added to LUP
2021-08-30 12:06:33
date last changed
2021-08-30 12:06:33
@misc{9064144,
  author       = {{Andersson, Samuel}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Divergence in coding sequence of different functional categories of immune genes between species of the order Rodentia}},
  year         = {{2021}},
}