Abstract
In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2–T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters. Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence.Graphical abstract
Highlights
The genetic code is a set of rules that defines how the fourletter code of DNA is translated into the 20-letter code of protein [1, 2]
All coding genes could be divided into two unequal clusters according to the relative base frequencies of A and T at the second codon position, and the coding genes in the two clusters exhibited significant difference in protein functions [29]
Comparison of proteins encoded in numbers of complete genomes from many major phylogenetic lineages and elucidation of consistent patterns of sequence similarities allows the delineation of many clusters of orthologous groups (COGs) [31]
Summary
The genetic code is a set of rules that defines how the fourletter code of DNA is translated into the 20-letter code of protein [1, 2]. Codon degeneracy mainly manifests at this position and among the synonymous codons, the one matching the most abundant tRNA usually has the highest frequency [13] This coupling pattern has been thought to benefit translation efficiency [14]. All coding genes could be divided into two unequal clusters according to the relative base frequencies of A and T at the second codon position, and the coding genes in the two clusters exhibited significant difference in protein functions [29]. We hypothesized that this pattern might appear widely in the prokaryotic domain and that it could be connected with gene function. We revealed a consistent of A 2–T2 associated clustering pattern and consistent functional influence in prokaryotes
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