Biological function in the twilight zone of sequence conservation

Abstract

Strong DNA conservation among divergent species is an indicator of enduring functionality. With weaker sequence conservation we enter a vast ‘twilight zone’ in which sequence subject to transient or lower constraint cannot be distinguished easily from neutrally evolving, non-functional sequence. Twilight zone functional sequence is illuminated instead by principles of selective constraint and positive selection using genomic data acquired from within a species’ population. Application of these principles reveals that despite being biochemically active, most twilight zone sequence is not functional.

Conservation of gene architecture and domains amidst sequence divergence in thehsrωlncRNA gene across theDrosophilagenus: Anin silicoanalysis

“…The present bioinformatic analysis also revealed that the hsrω gene associated repeats were the most variable component in spite of their being unique to this gene. The lack of any significant sequence similarity between the tandem repeats associated with hsrω gene in different species is in agreement with the widely known rapid diversification of repeat sequences during speciation (Chen, et al, 2016;Chodroff, et al, 2010;Corona-Gomez, et al, 2019;Haerty and Ponting, 2013;Kapusta and Feschotte, 2014;Ponting, 2017;Tavares, et al, 2019;Zhang, et al, 2017).…”

“…It is now generally recognized that compared to the relatively high sequence conservation in protein-coding and a few non-coding genes due to purifying selection, majority of the lncRNA genes show little conservation in their transcribed sequences except for small domains (Chen, et al, 2016;Chodroff, et al, 2010;Corona-Gomez, et al, 2019;Haerty and Ponting, 2013;Kapusta and Feschotte, 2014;Ponting, 2017;Zhang, et al, 2017). Our analysis of the nucleotide sequence of the relatively large hsrω lncRNA gene in the genus Drosophila revealed a comparably peppered sequence conservation amidst a similar architecture.…”

Intelligent Design of 14-3-3 Docking Proteins Utilizing Synthetic Evolution Artificial Intelligence (SYN-AI)

“…Where, it has been assumed that highly evolutionarily conserved residues are critical to protein function. [15][16][17][18][19][20][21][22][23] Thusly, SYN-AI is based upon the hypothesis that evolution conservation is an artifact of the evolution force. Classically, wobble has been defined by genetic diversity in the third codon with conservation of residue sequence.…”

Fundamental Theory of the Evolution Force (FTEF): Gene Engineering utilizing Synthetic Evolution Artificial Intelligence (SYN-AI)

“…In constructing our model, consideration of evolution force was limited to what we believe to be the four most fundamental molecular based evolution engines, (i) evolution conservation, (ii) wobble, (iii) DNA binding state and (iv) periodicity. Whereby, strong association between evolutional conservation of DNA/protein sequence and effects on function has long been recognized by molecular biologist (1)(2)(3)(4)(5).…”