129 research outputs found
Homeostasis as the Mechanism of Evolution.
Homeostasis is conventionally thought of merely as a synchronic (same time) servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time) mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology
Unveiling Human Non-Random Genome Editing Mechanisms Activated in Response to Chronic Environmental Changes: I. Where Might These Mechanisms Come from and What Might They Have Led To?
none1noThis article challenges the notion of the randomness of mutations in eukaryotic cells by unveiling stress-induced human non-random genome editing mechanisms. To account for the existence of such mechanisms, I have developed molecular concepts of the cell environment and cell environmental stressors and, making use of a large quantity of published data, hypothesised the origin of some crucial biological leaps along the evolutionary path of life on Earth under the pressure of natural selection, in particular, (1) virus-cell mating as a primordial form of sexual recombination and symbiosis; (2) Lamarckian CRISPR-Cas systems; (3) eukaryotic gene development; (4) antiviral activity of retrotransposon-guided mutagenic enzymes; and finally, (5) the exaptation of antiviral mutagenic mechanisms to stress-induced genome editing mechanisms directed at "hyper-transcribed" endogenous genes. Genes transcribed at their maximum rate (hyper-transcribed), yet still unable to meet new chronic environmental demands generated by "pollution", are inadequate and generate more and more intronic retrotransposon transcripts. In this scenario, RNA-guided mutagenic enzymes (e.g., Apolipoprotein B mRNA editing catalytic polypeptide-like enzymes, APOBECs), which have been shown to bind to retrotransposon RNA-repetitive sequences, would be surgically targeted by intronic retrotransposons on opened chromatin regions of the same "hyper-transcribed" genes. RNA-guided mutagenic enzymes may therefore "Lamarkianly" generate single nucleotide polymorphisms (SNP) and gene copy number variations (CNV), as well as transposon transposition and chromosomal translocations in the restricted areas of hyper-functional and inadequate genes, leaving intact the rest of the genome. CNV and SNP of hyper-transcribed genes may allow cells to surgically explore a new fitness scenario, which increases their adaptability to stressful environmental conditions. Like the mechanisms of immunoglobulin somatic hypermutation, non-random genome editing mechanisms may generate several cell mutants, and those codifying for the most environmentally adequate proteins would have a survival advantage and would therefore be Darwinianly selected. Non-random genome editing mechanisms represent tools of evolvability leading to organismal adaptation including transgenerational non-Mendelian gene transmission or to death of environmentally inadequate genomes. They are a link between environmental changes and biological novelty and plasticity, finally providing a molecular basis to reconcile gene-centred and "ecological" views of evolution.openZamai, LorisZamai, Lori
Genetic analysis of retinal traits
Retina is a unique site in the human body where the microcirculation can be imaged
directly and non-invasively, allowing us to study in vivo the structure and pathology of
the human microcirculation. Retinal images can be quantitatively assessed with
computerized imaging techniques, enabling us to measure several different quantitative
traits derived from the retinal vasculature. Arterial and venular calibres are the most
extensively studied traits of the retinal microvasculature and numerous epidemiological
studies demonstrated promising associations with systemic and ocular diseases as well
as with disease markers. However, there has been a lack of research into
pathophysiological processes leading to retinal vascular signs, and how they link retinal
microcirculation with coronary and cerebral microvasculature change. Information about
genetic determinants underlying retinal vascular structure is therefore important for
understanding the processes leading to microvascular pathophysiology. Two genome
wide association studies have been published so far revealing four loci associated with
retinal venular calibre and one locus with arteriolar calibre. Here the results from the
genome-wide association analysis of 10 different retinal vessel traits in two population
based cohorts are presented. Retinal images were measured in non-mydriatic fundus
images from 808 subjects in the Orkney Complex Disease Study (ORCADES) and 390
subjects from the Croatian island of Korcula, using the semi-automated retinal
vasculature measurement programme SIVA and VAMPIRE. Using pairwise estimates of
kinship based on genomic sharing, heritability was calculated for each trait. Estimates of
tortuosity measure and fractal dimensions present first published reports of heritability
estimates for those traits. In addition correlation analysis with systemic risk factor was
also completed, confirming already published results as well as revealing some new
associations. A genome wide association analysis of retinal arteriolar width revealed a
genome wide significant hit (1.8x10-7) in a region of chromosome 2q32 (within TTN
gene). Replication was sought in a further independent Scottish population (LBC) and
additional 400 retinal images were graded. The result did not replicate, however the
direction of the effect was consistent and a larger sample size is required. Analysis of the
remaining traits did not yield genome wide significant result,s and will also require
larger sample sizes.
Genetic analysis of a binary retinal trait was also explored in a case control study of
retinal detachment, which is an important cause of vision loss. A two-stage genetic
association discovery phase followed by a replication phase in a combined total of 2,833
RRD cases and 7,871 controls was carried out. None of the SNPs tested in the discovery
phase reached the threshold for association. Further testing was carried out in
independent case-control series from London (846 cases) and Croatia (120 cases). The
combined meta-analysis identified one association reaching genome-wide significance
for rs267738 (OR=1.29, p=2.11x10-8), a missense coding SNP and eQTL for CERS2
encoding the protein ceramide synthase 2. Additional genetic risk score, pathway
analysis and genetic liability analysis were also carried out
Emergence and the human genome
Peer reviewedThe (human) genome functions as an open system within human nutritional, economic, cultural, intellectual and
emotional contexts. Of profound importance is the extent of free will that emerged with our cognitive and
consciousness traits. We have been instrumental in creating particular environments and semiotics according to
which we live and with which our genes are expressed. The possibility exists that an information continuum
between genes, brain and environment may follow quantum rules and exhibit correlated properties that result in
coordinated behaviour (entanglement), even without signal transfer or interaction. With the unprecedented
technological advances made during the last century, for the first time a biological organism can, in theory,
purposefully design its own future evolution. This is likely to remain limited by ultimate unpredictability due to
emergent novelties arising during the process. The effect(s) of a strong human strategic guiding influence, however,
implies a tremendous moral responsibility to help shape future outcomes which will enhance the continued existence
of quality Life on Earth. How are we doing so far, and how can we exploit knowledge of the possible structural basis
of genomic memory and the principles linked with self organisation and emergence to avoid recurrence of outcomes
previously shown to have had negative consequences for Life. Can we feed back crucial brain memories to the
germline contrary to prevailing dogma, and does this contribute to a compound interest situation not only of
intellectual ability but also of a hereditary basis for augmenting ("negative", Machiavellian type) moral behaviour
previously found to be successful for pure biological survival?Research Institute for Theology and Religio
- …