Theoretically, larger genes are more susceptible to mutations than smaller genes. Why?
Simplistically it may seem that gene size is a large factor just because cosmic radiation is random so the damage caused by radiation and its by products will be greater because the target size is greater. While this is true there are many other factors so larger genes have a higher chance of containing sequences that can expand ( CCG expansion in fragile X) or problems caused by viral dna sequences within the larger genes (FMD) and large genes often have a lot of small exons so errors in splicing are more common because there are more splicing motifs to mutate and also more chance of splicing going wrong. Another factor is CpG methylation . the CpG site is very easily deaminated when it is methylated to thymidine so it can be the case that a small gene with a high CpG content will have a much higher mutation rate than a much larger gene with a low CpG content. Small genes like FRGR3 ( achondroplasia) and FGFR2 (apert syndrome) are interesting. The rate of CpG conversion in Apert syndrome is about 500-800 times higher than the usual CpG rate of mutation and is dependent on Paternal age so other factors can have a large effect on the rate of mutation even in small genes
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Genome sizes and mutation rates co-vary across all domains of life. In unicellular organisms and DNA viruses, they show an inverse relationship known as Drake’s rule.
You may check this paper as well: https://www.nature.com/articles/258359a0
Simplistically it may seem that gene size is a large factor just because cosmic radiation is random so the damage caused by radiation and its by products will be greater because the target size is greater. While this is true there are many other factors so larger genes have a higher chance of containing sequences that can expand ( CCG expansion in fragile X) or problems caused by viral dna sequences within the larger genes (FMD) and large genes often have a lot of small exons so errors in splicing are more common because there are more splicing motifs to mutate and also more chance of splicing going wrong. Another factor is CpG methylation . the CpG site is very easily deaminated when it is methylated to thymidine so it can be the case that a small gene with a high CpG content will have a much higher mutation rate than a much larger gene with a low CpG content. Small genes like FRGR3 ( achondroplasia) and FGFR2 (apert syndrome) are interesting. The rate of CpG conversion in Apert syndrome is about 500-800 times higher than the usual CpG rate of mutation and is dependent on Paternal age so other factors can have a large effect on the rate of mutation even in small genes
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Theoretically, yes. However, the mutation rate depends on the location in the chromosome, GC content, presence or absence of transposons, repeat regions, etc. This is a BIG question. Time to hit the books and learn the literature!
Yes, as you mentioned , the largest genes are more susceptible to be highly mutated due to as the gene increased in size , GC contents, transposons elements , repeated sequences, epigentic effects, misreading during replication and transcription ,.....etc were increased but by anyway, many factors affecting the mutation rate rather the the size of the genes
Dear all...
I'm deeply appreciated for your answers which were so helpful.
Books are not the only way to learn!! Questions, Answers.. even Notes can be valuable, and that what RG platform is!! it's another way to communicate and learn. I will keep learning from your experiences.
I agree with Katie. The literature (books and published papers) is required knowledge. One cannot simply talk amongst ones peers or do lab experiments and expect to understand the system of interest. Dig deep into the literature!! Stay current with literature, but also read relevant books and publications from previous decades. That helps one understand the foundations of one's topic.
You are right, there are many ways to learn. Folks with simple questions can come here for advice and simple answers. You have a big, complex question that does NOT have a simple answer. The experts on Research Gate are telling you to go read the literature. You need to become an expert in your topic. Best of luck!
Dear Katie (THE EXPERT)...
It's simple, when you find any statement not fit with your logic (which is not ideal always), you can just pass through!!! We may find some questions "BIG" because it's beyond our capabilities "EXPERIENCE", but we still have a chance to show our experts by dressing a simple answer for such "BIG" question!!!!
Wish You All the Best Katie,
Ayoob.
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