A collaborative research effort between two CST research entities resulted in publication in the prestigious Proceedings of the National Academy of Sciences (PNAS). The paper, titled "Weak selection on synonymous codons substantially inflates dN/dS estimates in bacteria" is authored by Shakibur Rahman, a biology major, Professor Sergei Pond of iGEM and postdoc Andrew Webb and Professor Jody Hey of CCGG.
Rahman, a rising senior with a minor in German language and cultural studies, recently shared his thoughts on research, why he chose CST and Temple University and his plans for the future.
How long have you been working in Dr. Hey's lab? What attracted you to their work?
I have been working in the Hey lab since roughly October 2018, fall of my freshman year. I was attracted to this lab in particular because although I had no prior experience with coding, it was a skill that I definitely wanted to work on and I figured that by starting at the beginning of my freshman year, I would have a lot of time to try to gain proficiency with coding. I also thought the project was interesting as well.
Can you describe the research?
This research is essentially the analysis of synonymous substitutions, which are codon changes that result in the translation of the same amino acid, and codon usage in 13 somewhat closely related species of bacteria.
We took the existing method for estimating the strength of natural selection on genes and modified it so it could account for more factors and therefore be more accurate. We categorized synonymous substitutions as either neutral or selected under a multiclass synonymous substitution model abbreviated as MSS instead of assuming all synonymous substitutions are strictly neutral.
The nonsynonymous to synonymous substitution ratio was compared between the MSS model and the standard codon model with the neutral assumption. A nonsynonymous substitution is a codon change that results in the translation of a different amino acid.
An overestimation of the dN/dS ratio was found in calculations using the standard codon model with the MSS model being on average 80 percent of the standard ratio. The explanation for the codon bias variation or the selection of synonymous substitutions was found to be due to very weak selection.
Why is this paper significant?
There are many papers that use the assumption that synonymous substitutions in bacteria are neutral instead of the possible categories of neutral and selected. This can lead to an over inflation calculation of the dN/dS ratio which is often a measure of whether there is positive or negative selection and the strength of selection in a population.
An overinflated dN/dS ratio would result in an overestimation of positive selection in a species and also an underestimation of the strength of negative selection. We found a way to identify a good control group for which codon changes are not affected by natural selection and by using this group, we could better estimate the strength of natural selection.
Is this your first publication? How does it feel to be first author?
This is my first publication and my first real experience with research in general. It feels somewhat surreal and very rewarding to be first author although the project was definitely a group effort.
How did you find your way to Temple? What made you want to come to CST?
I came to Temple for a few reasons. My old brother was a freshman at Temple when I applied, and the university is close enough to home where I could still see family but far enough away for me to mature away from them. It was also an affordable option and had the major and minor I wanted to pursue.
I came to CST because I have also been very interested in biology and a lot of classes also overlap with pre-med requirements. I also appreciated Temple's emphasis on research.
What are your career goals?
I am applying for the 2022 medical school admissions cycle with the ultimate hope of becoming a cardiothoracic surgeon. I also hope to continue with research in some capacity throughout medical school and while I am a surgeon, if that does happen.