How do I determine the optimal gene-to-vector ratio for ligation?

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Discussion Overview

The discussion centers around determining the optimal gene-to-vector ratio for ligation in molecular biology, specifically for ligating a gene fragment into a Pbluescript plasmid. Participants explore various ratios, methodologies, and resources related to this process.

Discussion Character

  • Technical explanation
  • Experimental/applied
  • Debate/contested

Main Points Raised

  • One participant notes the importance of the gene-to-vector ratio and seeks guidance on what the optimal relationship should be.
  • Another participant suggests that the ratio can vary widely, from 8:1 to 1:8 (plasmid:insert), and provides a formula for calculating the amount of insert needed based on the vector and insert sizes.
  • A different participant recommends trying several ratios simultaneously, suggesting a common starting point of 1 vector to 3 insert, and testing ratios such as 1:3, 1:5, 1:7, and 1:9.
  • One participant mentions the utility of conducting a ligation without an insert to assess self-ligation of the vector.
  • A participant shares a link to a website that may provide additional help on this topic, while also noting its limited activity and response rate.

Areas of Agreement / Disagreement

Participants generally agree on the need to experiment with different ratios, but there is no consensus on a single optimal ratio, as various suggestions are offered.

Contextual Notes

Participants express uncertainty regarding the best ratio and the effectiveness of different approaches, indicating that results may vary based on specific experimental conditions.

rockind78
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I will be attempting to ligate a gene fragment (~650bp's) into a Pbluescript plasmid here in the next day or so. The fragment and the vector have both already been digested and purified, so that's not an issue. However, I have been advised by a number of different people that the concentrations of my gene relative to my vector are VERY important and I do not know what this relationship is supposed to be. I looked in the Short Protocols Molecular Biology and did not find anything. Does anyone have any good links or words of wisdom? Thanks!

Dustan
 
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There a ratio that you should follow according to the protocols. Ratio can vary from 8:1 to 1:8 (plasmid:insert).

Here the formula to calculate the amount needed

ngofvector × kbsizeofinsert × insert:vector molar ratio = ng of insert
----------------------------
kb size of vector

You usually have to work you ratio out. What we do in the lab, we set 3 or 4 differrent reaction, we keep the plasmid volume the same (usually 1 uL) and we use a range of volume for the insert (usually 1 uL, 2uL, 4uL). Then we see what works best and reuse it if necessary.
 
Thank you Ian. I appreciate the quick response. I will look at my protocols again to see if I missed something.
 
I think the usual thing is 1 vector : 3 insert.. but the best thing is to try several at the same time and see which one gives you the best enrichement (as Ian said).

Try one ligation without insert (to see self closing vectors) and then you could do 1:3, 1:5, maybe 1:7 and 1:9
 
As for a link: http://micro.nwfsc.noaa.gov/forums/index.php?sid=5a9ee6c992acccf932b83f1b3aa98383 is the only website that I have ever found that seems to be dedicated to helping people figure out questions like that (And i think I only found this website because Ian pointed me towards it many many months ago).

It's a nice website in theory, Forums like these where people ask questions and get answers, unfortunately it isn't as active as you would like, and so you aren't guaranteed a response.
 
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