Can all heritable biology really be reduced to a single dimension?

A long-held presupposition in the field of bioinformatics holds that genetic, and now even epigenetic 'information' can be abstracted from the physicochemical details of the macromolecular polymers in which it resides. It is perhaps rather ironic that this basic conjecture originated upon the first observations of DNA structure itself. This static model of DNA led very quickly to the conclusion that only the nucleobase sequence itself is rich enough in molecular complexity to replicate a complex biology. This idea has been pervasive throughout genomic science, higher education and popular culture ever since; to the point that most of us would accept it unquestioningly as fact. What is more alarming is that this conjecture is driving a significant portion of the technological development in modern genomics towards methods strongly rooted in DNA sequencing, thereby reducing a dynamic multi-dimensional biology into single-dimensional forms of data. Evidence countering this central tenet of bioinformatics has been quietly mounting over many decades, prompting some to propose that the genome must be studied from the perspective of its molecular reality, rather than as a body of information to be represented symbolically. Here, we explore the epistemological boundary between bioinformatics and molecular biology, and warn against an 'overtly' bioinformatic perspective. We review a selection of new bioinformatic methods that move beyond sequence-based approaches to include consideration of databased three dimensional structures. However, we also note that these hybrid methods still ignore the most important element of gene function when attempting to improve outcomes; the fourth dimension of molecular dynamics over time.

Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context.

Visual outcomes and patient satisfaction after implantable collamer lens and Toric implantable collamer lens correction for moderate to high myopia and myopic astigmatism.

OBJECTIVE: To compare preoperative and postoperative visual outcomes, determine patient's satisfaction, and evaluate visual symptoms after implantable collamer lens (ICL) implantation. METHODS: One hundred and twelve patients with myopia between -2.75 and -19.50 diopter had ICL or Toric ICL (TICL) implantation. The implantations were carried out at the Cornea and Refractive Unit, Magrabi Eye Hospital, Sana'a, Republic of Yemen between September 2007 and October 2010. Preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), and refraction was evaluated. Patient's satisfaction and visual symptoms were evaluated using a questionnaire. RESULTS: The mean age was 26.74 +/- 5.6 years. The mean preoperative UCVA improved from 0.01 +/- 0.04 to 0.75 +/- 0.22. The mean postoperative UCVA (0.75 +/- 0.23) versus preoperative BSCVA (0.61 +/- 0.23) had a significant statistical change (p<0.001), and Pearson correlation of 0.818. Preoperative BSCVA versus postoperative BSCVA gained 5 lines in 2.5%, 4 lines in 4.4%, 3 lines in 14.2%, 2 lines in 32.8%, and one line improvement in 24%, whereas it was maintained in 20.1%, and lost one or more lines in 2%. The mean score for the overall satisfaction was 2.67 +/- 0.45. A total of 15.2% reported complaint of halos, 13.4% reported perception of stars around lights, and 23.2% had glare. CONCLUSION: Implantation of ICL and TICL is safe and effective and provides predictable refractive results with good satisfaction in the treatment of moderate to high myopia, suggesting its viability as a surgical option for the treatment of myopia.