Synonymous codon selection bias and its impact on evolutionary co-translational protein folding
(2024) BINP51 20232Degree Projects in Bioinformatics
- Abstract
- Protein biosynthesis follows a hierarchical process, as genes are transcribed into mRNA, translated into a chain of amino acids, and ultimately folded into functional proteins. This implies that the protein structure is merely determined by the amino acid sequence. Yet, studies on translation efficiency indicate that codon usage, which is organism dependent, significantly impacts protein folding kinetics. On the translational level, inadequately used codons can lead to differences in translation and elongation speed, thus leading to misfolded proteins, which can relate to diseases, like cystic fibrosis. Computational analysis to understand how certain motifs in codons and protein structures relate are limited, as these two levels have been... (More)
- Protein biosynthesis follows a hierarchical process, as genes are transcribed into mRNA, translated into a chain of amino acids, and ultimately folded into functional proteins. This implies that the protein structure is merely determined by the amino acid sequence. Yet, studies on translation efficiency indicate that codon usage, which is organism dependent, significantly impacts protein folding kinetics. On the translational level, inadequately used codons can lead to differences in translation and elongation speed, thus leading to misfolded proteins, which can relate to diseases, like cystic fibrosis. Computational analysis to understand how certain motifs in codons and protein structures relate are limited, as these two levels have been mostly separated in existing in silico studies.
Annotated coding sequences for experimentally determined and in silico predicted protein structures were directly acquired from their main sources, enabling a wider analysis of codon usage’s impact on protein folding. The dataset was used in a variety of statistical analysis, including the study of relative synonymous codon usage values within structure motifs and along the sequence. Since rare or not frequently used codons are under selective pressure, as they decrease protein translation speed and their expression, it was studied if especially those under a defined threshold correlate significantly with the structure of a protein. Multiple sequence alignments of protein families were used to calculate the degree of codon rarity and identify correlation for individual secondary structure elements, fold classes and domains.
It was found that the impact is based on the location of a sequence and synonymous codon specific. The phylogenetic of protein families evolve towards more rare codons, while being also domain and fold class dependent. (Less) - Popular Abstract
- Understanding codon impact on protein structure and evolution
Proteins are synthesized inside cells based on the genetic information, stored in genes, which are first transcribed to messenger RNA and then translated to a chain of amino acids, which form into a 3-dimensional structure, the functional protein. The translation is done on 3 nucleotides (A, C, T or G) in the mRNA sequence, which encode 1 of 20 amino acids. There are 64 codons encoding 20 amino acids, so some of the amino acids can be translated by multiple codons, which are also called synonymous.
Synonymous codons are not equally used to translate an amino acid, due to species specific bias. This codon usage bias has formed over evolution, due to mutational bias or... (More) - Understanding codon impact on protein structure and evolution
Proteins are synthesized inside cells based on the genetic information, stored in genes, which are first transcribed to messenger RNA and then translated to a chain of amino acids, which form into a 3-dimensional structure, the functional protein. The translation is done on 3 nucleotides (A, C, T or G) in the mRNA sequence, which encode 1 of 20 amino acids. There are 64 codons encoding 20 amino acids, so some of the amino acids can be translated by multiple codons, which are also called synonymous.
Synonymous codons are not equally used to translate an amino acid, due to species specific bias. This codon usage bias has formed over evolution, due to mutational bias or natural selection. Another reason for codon usage bias as research has found, is the significant role of codons during translation. More frequently used codons by the species are translated faster and promote protein expression, while rare codons can slow down or even pause the translation process. Consequently, rare codons are thought to be disadvantageous but contrary help forming the proteins into a correct and functional shape. This is because a fast/ slow translation pattern ensures proper co-translational (simultaneously to the translation process) folding of the growing protein. A change in the synonymous codon along the mRNA, also known as a silent mutation, can not only influence the protein structure but also lead to diseases like cystic fibrosis.
Studying the impacts of codons on structure is challenging due to missing resources and the indirect influence, compared to amino acid mutations. The project investigated, based on a large-scale computational analysis, the relationship of synonymous codons with the secondary structures and the occurrence of rare codons in protein families, domains and fold classes. The result is a new resource for protein structures and codons, as well as insights that the presence or conservation of a codon is structure dependent and co-evolves with protein families. The project helps to better understand how codon usage and protein structure correspond to each other.
Master’s Degree Project in Bioinformatics 45 credits 2024 Department of Biology, Lund University
Advisor: Ingemar André and Heléne Bret
Department of Biochemistry and Structural Biology, CMPS, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9185171
- author
- Fastus, Dominique
- supervisor
- organization
- course
- BINP51 20232
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9185171
- date added to LUP
- 2025-02-13 15:36:37
- date last changed
- 2025-02-13 15:36:37
@misc{9185171,
abstract = {{Protein biosynthesis follows a hierarchical process, as genes are transcribed into mRNA, translated into a chain of amino acids, and ultimately folded into functional proteins. This implies that the protein structure is merely determined by the amino acid sequence. Yet, studies on translation efficiency indicate that codon usage, which is organism dependent, significantly impacts protein folding kinetics. On the translational level, inadequately used codons can lead to differences in translation and elongation speed, thus leading to misfolded proteins, which can relate to diseases, like cystic fibrosis. Computational analysis to understand how certain motifs in codons and protein structures relate are limited, as these two levels have been mostly separated in existing in silico studies.
Annotated coding sequences for experimentally determined and in silico predicted protein structures were directly acquired from their main sources, enabling a wider analysis of codon usage’s impact on protein folding. The dataset was used in a variety of statistical analysis, including the study of relative synonymous codon usage values within structure motifs and along the sequence. Since rare or not frequently used codons are under selective pressure, as they decrease protein translation speed and their expression, it was studied if especially those under a defined threshold correlate significantly with the structure of a protein. Multiple sequence alignments of protein families were used to calculate the degree of codon rarity and identify correlation for individual secondary structure elements, fold classes and domains.
It was found that the impact is based on the location of a sequence and synonymous codon specific. The phylogenetic of protein families evolve towards more rare codons, while being also domain and fold class dependent.}},
author = {{Fastus, Dominique}},
language = {{eng}},
note = {{Student Paper}},
title = {{Synonymous codon selection bias and its impact on evolutionary co-translational protein folding}},
year = {{2024}},
}