Mutation (Evolutionary Biology)

The steroid 5 alpha reductase encoded by SRD5A2 gene plays a critical role in male sex differentiation and mutation happened in the gene might also be one of the major causes of transexualism. In order to make this evident, a small study was designed. Blood samples were collected from normal people as well as transgenders, from which DNA was isolated by Miller’s method. From the DNA samples, the SRD5A2 gene was amplified using site specific primers and the amplified gene products were then sequenced. The sequences from the transgender samples were compared with the respective controls using the Bioedit tool. This study revealed the presence of few previously reported mutations on the transsexuals which clearly states that the mutation in the SRD5A2 gene was one of the vital causes for the transexualism.

For many astronomers, the progressive development of life has been seen as a natural occurrence given proper environmental conditions on a planet: even though such beings would not be identical to humans, there would be significant parallels. A striking contrast is seen in writings of nonphysical scientists, who have held more widely differing views. But within this diversity, reasons for differences become more apparent when we see how views about extraterrestrials can be related to the differential emphasis placed on modern evolutionary theory by scientists of various disciplines. One clue to understanding the differences between the biologists, paleontologists, and anthropologists who speculated on extraterrestrials is suggested by noting who wrote on the subject. Given the relatively small number of commentators on the topic, it seems more than coincidental that four of the major contributors to the evolutionary synthesis in the 1930s and 1940s are among them. Upon closer examination it is evident that the exobiological arguments of Theodosius Dobzhansky and George Gaylord Simpson and, less directly, of H. J. Muller and Ernst Mayr are all related to their earlier work in formulating synthetic evolution. By examining the variety of views held by nonphysical scientists, we can see that there were significant disagreements between them about evolution into the 1960s. By the mid-1980s, many believed that “higher” life, particularly intelligent life, probably occurs quite infrequently in the universe; nevertheless, some held out the possibility that convergence of intelligence could occur across worlds. Regardless of the final conclusions these scientists reached about the likely prevalence of extraterrestrial intelligence, the use of evolutionary arguments to support their positions became increasingly common.

Industrialisation leads to relaxed selection and thus the accumulation of fitness-damaging genetic mutations. We argue that religion is a selected trait that would be highly sensitive to mutational load. We further argue that a specific form of religiousness was selected for in complex societies up until industrialisation based around the collective worship of moral gods. With the relaxation of selection, we predict the degeneration of this form of religion and diverse deviations from it. These deviations, however, would correlate with the same indicators because they would all be underpinned by mutational load. We test this hypothesis using two very different deviations: atheism and paranormal belief. We examine associations between these deviations and four indicators of mutational load: (1) poor general health, (2) autism, (3) fluctuating asymmetry, and (4) left-handed-ness. A systematic literature review combined with primary research on handedness demonstrates that atheism and/or paranormal belief is associated with all of these indicators of high mutational load.

In computer search optimization theory, active information is a measurement of a search algorithm's internal information as it relates to its problem space. While it has been previously applied to evolutionary search algorithms on computers, it has not been applied yet to biological systems. Active information can be very useful in differentiating between mutational adaptations which are based on internally-coded information and those which are the results of happenstance. However, biological systems present many practical problems regarding measuring active information which are not present in digital systems. This paper describes active information, how it can be used in biology, and how some of these problems can be overcome in specific cases.

Mutations that occur in the absence of selection have often been cited as evidence that mutations are philosophically random - that is, that they do not follow a predetermined pattern but occur haphazardly.  Mutation in absence of selection, however, may be a part of an adaptation process, specifically engineered for maintaining variability in organisms as a hedge against future environmental changes.  A statistically random distribution of a constrained set of semi-specific (i.e. nonphilosophically random) mutations in populations would enable them to preserve a fairly constant percentage of mutants, which would foster survival in adverse conditions.

The rediscovery of Mendel’s laws a century ago launched the science that William Bateson called “genetics”, and led to a new view of evolution combining selection, particulate inheritance, and the newly characterized phenomenon of “mutation”.  This “mutationist” view clashed with the earlier view of Darwin, and the later “Modern Synthesis”, by allowing discontinuity, and by recognizing mutation (or more properly, mutation-and-altered-development) as a source of creativity, direction, and initiative.  By the mid-20th century, the opposing Modern Synthesis view was a prevailing orthodoxy: under its influence, “evolution” was redefined as “shifting gene frequencies”, i.e., the sorting out of pre-existing variation without new mutations, and the notion that mutation-and-altered-development can exert a predictable influence on the course of evolutionary change was seen as heretical.  Nevertheless, mutationist ideas re-surfaced: the notion of mutational determinants of directionality emerged in molecular evolution by 1962, followed in the 1980’s by an interest among evolutionary developmental biologists in a shaping or creative role of developmental propensities of variation, and more recently, a recognition by theoretical evolutionary geneticists of the importance of discontinuity and of new mutations in adaptive dynamics.  The synthetic challenge presented by these innovations is to integrate mutation-and-altered-development into a new understanding of the dual causation of evolutionary change— a broader and more predictive understanding that already can lay claim to important empirical and theoretical results— and to develop a research program appropriately emphasizing the emergence of variation as a cause of propensities of evolutionary change.

Mutations are normally classified according to their proximal effect on an organism’s fitness, whether beneficial, deleterious, or neutral. While this is a very useful first-pass categorization of mutations, the realization that mutations are not always haphazard, but in fact may be part of a regulated design, means that creationists should be looking for a deeper classification of mutations based on whether or not they conform to their organism’s design. Design-consistent mutations are those which occur within the pattern expected by the genome’s architecture, and design-inconsistent mutations are those which occur outside of the genome’s architecture. Features such as metabolic consistency, mutational mechanism, mutation rate, reversibility, and preservation of genome semantics can be used by biologists to assess whether or not a mutation is design-consistent or design-inconsistent.

In a recent paper (1) it was argued that in order to mutate to more enhanced organisms an organism must have some mechanisms, just as the sender or mutative influences to be able to receive, implement and make mutative impacts active. The conclusion was that this was not observed and thus that evolution must be part of pseudo scientifically assumptions. One can believe it as many people also actively do. But then evolution must be considered as a religion and not part of correct science. On top of that, it also should be treated in society as such and not be taught as correct science to gullible people such as children. In order to prove this statement an research was conducted parallel to that paper. Which is partially presented here. If mutations enhance organisms that this must be visible in mutations with humans. On his case study of syndromes the syndromes have been evaluated whether or not a syndrome was genetically originated or not. There are about 1400+ syndromes known (2) and how ever this is a preliminairy result, since only half of the data has been it can already be estimated that the majority of syndromes is of genetic origin. About maximum 74% is genetically originated.

Synthetic theory in its classical version hypothesized mutational events as strictly casual, and therefore constant mutation rate during organic evolution. Nevertheless, Barbara Mc Clintock (1984) argued that the mutation rate can increase when cells, tissues, or organisms are challenged, mainly as a consequence of transposons activity.

In the last decades, an amount of studies has shown that some new molecular mechanisms can lead in different organisms to a variation in mutation rate (see e.g. Rodrigo S. Galhardo et. al, 2007). On the other hand, John H. Holland (1975) originally suggested this it is often beneficial to change the mutation rate in a simple genetic algorithm.

The goal of the project is to show that an increase in a mutation rate can help a simple biological model to adapt to its environment. I mean as “adaptation” the process leading to a “structural coupling” of a biological system with its environment, as described by Maturana and Varela (1972) so no fitness index is used, and the adaptation, if any,  should be an emergent phenomenon.

Classical homocystinuria is caused by mutations in the cystathionine β-synthase (CBS) gene. Previous experiments in bacterial and yeast cells showed that many mutant CBS enzymes misfold and that chemical chaperones enable proper folding of a number of mutations. In the present study, we tested the extent of misfolding of 27 CBS mutations previously tested in E. coli under the more folding-permissive conditions of mammalian CHO-K1 cells and the ability of chaperones to rescue the conformation of these mutations. Expression of mutations in mammalian cells increased the median activity 16-fold and the amount of tetramers 3.2-fold compared with expression in bacteria. Subsequently, we tested the responses of seven selected mutations to three compounds with chaperone-like activity. Aminooxyacetic acid and 4-phenylbutyric acid exhibited only a weak effect. In contrast, heme arginate substantially increased the formation of mutant CBS protein tetramers (up to sixfold) and rescued catalytic activity (up to ninefold) of five out of seven mutations (p.A114V, p.K102N, p.R125Q, p.R266K, and p.R369C). The greatest effect of heme arginate was observed for the mutation p.R125Q, which is non-responsive to in vivo treatment with vitamin B6. Moreover, the heme responsiveness of the p.R125Q mutation was confirmed in fibroblasts derived from a patient homozygous for this genetic variant. Based on these data, we propose that a distinct group of heme-responsive CBS mutations may exist and that the heme pocket of CBS may become an important target for designing novel therapies for homocystinuria.

Members of the Ty3-Gypsy retrotransposon family are rare in mammalian genomes despite their abundance in invertebrates and some vertebrates. These elements contain a gag-pol-like structure characteristic of retroviruses but have lost their ability to retrotranspose into the mammalian genome and are thought to be inactive relics of ancient retrotransposition events. One of these retrotransposon-like elements, PEG11 (also called RTL1) is located at the distal end of ovine chromosome 18 within an imprinted gene cluster that is highly conserved in placental mammals. The region contains several conserved imprinted genes including BEGAIN, DLK1, DAT, GTL2 (MEG3), PEG11 (RTL1), PEG11as, MEG8, MIRG and DIO3. An intergenic point mutation between DLK1 and GTL2 causes muscle hypertrophy in callipyge sheep and is associated with large changes in expression of the genes linked in cis between DLK1 and MEG8. It has been suggested that over-expression of DLK1 is the effector of the callipyge phenotype; however, PEG11 gene expression is also strongly correlated with the emergence of the muscling phenotype as a function of genotype, muscle type and developmental stage. To date, there has been no direct evidence that PEG11 encodes a protein, especially as its anti-sense transcript (PEG11as) contains six miRNA that cause cleavage of the PEG11 transcript. Using immunological and mass spectrometry approaches we have directly identified the full-length PEG11 protein from postnatal nuclear preparations of callipyge skeletal muscle and conclude that its over-expression may be involved in inducing muscle hypertrophy. The developmental expression pattern of the PEG11 gene is consistent with the callipyge mutation causing recapitulation of the normal fetal-like gene expression program during postnatal development. Analysis of the PEG11 sequence indicates strong conservation of the regions encoding the antisense microRNA and in at least two cases these correspond with structural or functional domains of the protein suggesting co-evolution of the sense and antisense genes.

Two key features of RNA viruses are their compacted genomes and their high mutation rate. Accordingly, deleterious mutations are common and have an enormous impact on viral fitness. In their multicellular hosts, robustness can be achieved by genomic redundancy , including gene duplication, diploidy, alternative metabolic pathways and biochemical buffering mechanisms. However, here we review evidence suggesting that during RNA virus evolution, alternative robustness mechanisms may have been selected. After briefly describing how genetic robustness can be quantified, we discuss mechanisms of intrinsic robustness arising as consequences of RNA-genome architecture, replication peculiarities and quasi-species population dynamics. These intrinsic robustness mechanisms operate efficiently at the population level, despite the mutational sensitivity shown by individual genomes. Finally, we discuss the possibility that viruses might exploit cellular buffering mechanisms for their own benefit, producing a sort of extrinsic robustness.

The lysosomal storage disorders are a group of 50 unique inherited diseases characterized by unseemly lipid storage in lysosomes. These malfunctions arise due to genetic mutations that result in deficiency or reduced activities of the lysosomal enzymes, which are responsible for catabolism of biological macromolecules. Sly syndrome or mucopolysaccharidosis type VII is a lysosomal storage disorder associated with the deficiency of β-glucuronidase (EC 3.2.1.31) that catalyzes the hydrolysis of β-D-glucuronic acid residues from the non-reducing terminal of glycosaminoglycan. The effects of the disease causing mutations on the framework of the sequences and structure of β-glucuronidase (GUSBp) were analyzed utilizing varieties of bioinformatics tools. These analyses showed that 211 mutations may result in alteration of the biological activity of GUSBp, including previously experimentally validated mutations. Finally, we refined 90 disease causing mutations, which presumably cause a significant impact on the structure, function, and stability of GUSBp. Stability analyses showed that mutations p.Phe208Pro, p.Phe539Gly, p.Leu622Gly, p.Ile499Gly and p.Ile586Gly caused highest impact on GUSBp stability and function because of destabilization of the protein structure. Furthermore, structures of wild type and mutant GUSBp were subjected to molecular dynamics simulation to examine the relative structural behaviors in the explicit conditions of water. In a broader view, the use of in silico approaches provided a useful understanding of the effect of single point mutations on the structure-function relationship of GUSBp.

One of the key tasks of creation biology is to understand the logic of creation itself - to comprehend the design of the Creator.  Functional adaptation and biological imperfection are two aspects of the created order of life for which any theory of creation must address (Wood and Murray, 2003).  One key issue in addressing these topics is differentiating between genetic changes which are functional adaptations and those which are a result of the curse.  Bartlett (2009) introduced a second-order mutational classification scheme to aid in such differentiation, noting that fitness measurements alone are insufficient to determine if a mutational mechanism is consistent or inconsistent with the overall design of the organism.  While many criteria in the classification scheme are measurable, mutational mechanism was not given a quantitative measurement.  Here we will use the Active Information metric introduced by Dembski and Marks (2009) to try to measure the mutational mechanism criteria quantitatively.

Active Information is a metric originally developed for computer search procedures which measures the amount of information that a search procedure contributes to finding an appropriate target.  A random search with uniform probability has no Active Information, a search which consistently leads away from its target has negative Active Information, and a search which consistently leads towards its target has positive Active Information.  Active Information is measured by comparing the probabilities of a search hitting its target with the probability of a random search hitting the same targets.  The difference in probability is expressed in bits, computed by log2(1/p).
Historically, Active Information has only been applied to computer-based evolutionary algorithms.  However, it can also be applied to biological systems.  Applying Active Information to the Somatic Hypermutation (SMH) process for refining binding sites during an immune response makes an excellent test case for using this concept biologically.  Because SMH primarily works by restricting the physical range of base pairs which it mutates, it simplifies the Active Information calculations.  One can simply subtract log2(SMH mutation space) from log2(whole genome search space) and estimate that the SMH process contributes approximately 22 bits of Active Information to the search.  Additional factors can complicate this estimate, such as taking into account the number of mutations required for hitting the target.
This is a surprise to some, because the SMH process uses a sort of “shotgun” approach to generating novelty.  But the point of active information is that, even though it is a shotgun approach, the changes are limited only to one gene, rather than spread out across the whole genome.  The active information is the amount of restriction that the process applies which contributes to the likelihood of finding a target.  Searches that are more highly focused than SMH would have more active information, and those that are less focused would have less. 

The same idea can be applied to other mutational processes, such as the SOS response system in bacteria.  However, because in many of these systems the mutations are spaced throughout the genome, it is more difficult to calculate the Active Information involved.

Mutational processes which have zero or negative Active Information are probably not part of an organism’s design, while processes having large positive amounts of Active Information probably are.  In addition, comparing the amounts of Active Information in different types of mutational processes may help lead to a general theory of functional adaptation in creation biology.

Bibliography

• Bartlett, J. L.  2009.  Towards a Creationary Classification of Mutations.  Answers Research Journal 2:169-174.
• Dembski, W. A. and R. J. Marks.  2009.  Conservation of Information in Search: Measuring the Cost of Success.  IEEE Transactions on Systems, Man and Cybernetics A, Systems & Humans 5(5):1051-1061.
• Papavasiliou, F. N. and D. G. Schatz.  2002.  Somatic Hypermutation of Immunoglobulin Genes:  Merging Mechanisms for Genetic Diversity.  Cell 109(2, Supplement 1) 1:S35-S44.
• Wood, T. C. and M. J. Murray. 2003.  Understanding the Pattern of Life: Origins and Organization of the Species.  Broadman and Holman, Nashville.

The rediscovery of Mendel’s laws a century ago launched the science that William Bateson called “genetics”, and led to a new view of evolution combining selection, particulate inheritance, and the newly characterized phenomenon of “mutation”.  This “mutationist” view clashed with the earlier view of Darwin, and the later “Modern Synthesis”, by allowing discontinuity, and by recognizing mutation (or more properly, mutation-and-altered-development) as a source of creativity, direction, and initiative.  By the mid-20th century, the opposing Modern Synthesis view was a prevailing orthodoxy: under its influence, “evolution” was redefined as “shifting gene frequencies”, i.e., the sorting out of pre-existing variation without new mutations, and the notion that mutation-and-altered-development can exert a predictable influence on the course of evolutionary change was seen as heretical.  Nevertheless, mutationist ideas re-surfaced: the notion of mutational determinants of directionality emerged in molecular evolution by 1962, followed in the 1980’s by an interest among evolutionary developmental biologists in a shaping or creative role of developmental propensities of variation, and more recently, a recognition by theoretical evolutionary geneticists of the importance of discontinuity and of new mutations in adaptive dynamics.  The synthetic challenge presented by these innovations is to integrate mutation-and-altered-development into a new understanding of the dual causation of evolutionary change— a broader and more predictive understanding that already can lay claim to important empirical and theoretical results— and to develop a research program appropriately emphasizing the emergence of variation as a cause of propensities of evolutionary change.

Evolutionary trends responsible for systematic differences in genome and proteome composition have been attributed to GC:AT mutation bias in the context of neutral evolution, or to selection acting on genome composition.  A possibility that has been ignored, presumably because it is recognized neither in the Modern Synthesis nor in the Neutral Theory, is that mutation may impose a directional bias on adaptation.  This possibility is explored here with simulations of the effect of a GC:AT bias on amino acid composition during adaptive walks on an abstract protein fitness landscape called an “NK” model.  The results indicate that adaptation does not preclude mutation-biased evolution.  In the complete absence of neutral evolution, a modest GC:AT bias of realistic magnitude can displace the trajectory of adaptation in a mutationally favored direction, to such a degree that amino acid composition is biased substantially and persistently.  Thus, patterns of divergence suggesting mutational explanations do not require the hypothesis of neutral evolution.

With the development of high throughput sequencing technology, it becomes possible to directly analyze mutation distribution in a genome-wide fashion, dissociating mutation rate measurements from the traditional underlying assumptions. Here, we sequenced several genomes of Escherichia coli from colonies obtained after chemical mutagenesis and observed a strikingly nonrandom distribution of the induced mutations. These include long stretches of exclusively G to A or C to T transitions along the genome and orders of magnitude intra- and inter-genomic differences in mutation density. Whereas most of these observations can be explained by the known features of enzymatic processes, the others could reflect stochasticity in the molecular processes at the single-cell level. Our results demonstrate how analysis of the molecular records left in the genomes of the descendants of an individual mutagenized cell allows for genome-scale observations of fixation and segregation of mutations, as well as recombination events, in the single genome of their progenitor.

Variable numbers of tandem repeats (VNTR) typing is widely used for studying the bacterial cause of tuberculosis. Knowledge of the rate of mutation of VNTR loci facilitates the study of the evolution and epidemiology of Mycobacterium tuberculosis. Previous studies have applied population genetic models to estimate the mutation rate, leading to estimates varying widely from around [Formula: see text] to [Formula: see text] per locus per year. Resolving this issue using more detailed models and statistical methods would lead to improved inference in the molecular epidemiology of tuberculosis. Here, we use a model-based approach that incorporates two alternative forms of a stepwise mutation process for VNTR evolution within an epidemiological model of disease transmission. Using this model in a Bayesian framework we estimate the mutation rate of VNTR in M. tuberculosis from four published data sets of VNTR profiles from Albania, Iran, Morocco and Venezuela. In the first variant, the mutation rate increases linearly with respect to repeat numbers (linear model); in the second, the mutation rate is constant across repeat numbers (constant model). We find that under the constant model, the mean mutation rate per locus is [Formula: see text] (95% CI: [Formula: see text],[Formula: see text])and under the linear model, the mean mutation rate per locus per repeat unit is [Formula: see text] (95% CI: [Formula: see text],[Formula: see text]). These new estimates represent a high rate of mutation at VNTR loci compared to previous estimates. To compare the two models we use posterior predictive checks to ascertain which of the two models is better able to reproduce the observed data. From this procedure we find that the linear model performs better than the constant model. The general framework we use allows the possibility of extending the analysis to more complex models in the future.
Source: PubMed

Evolutionary biologists attribute much of the phenotypic diversity observed in nature to the action of natural selection. However, for many phenotypic traits, especially quantitative phenotypic traits, it has been challenging to test for the historical action of selection. An important challenge for biologists studying quantitative traits, therefore, is to distinguish between traits that have evolved under the influence of strong selection and those that have evolved neutrally. Most existing tests for selection employ molecular data, but selection also leaves a mark on the genetic architecture underlying a trait. In particular, the distribution of quantitative trait locus (QTL) effect sizes and the distribution of mutational effects together provide information regarding the history of selection. Despite the increasing availability of QTL and mutation accumulation data, such data have not yet been effectively exploited for this purpose. We present a model of the evolution of QTL and employ it to formulate a test for historical selection. To provide a baseline for neutral evolution of the trait, we estimate the distribution of mutational effects from mutation accumulation experiments. We then apply a maximum-likelihood-based method of inference to estimate the range of selection strengths under which such a distribution of mutations could generate the observed QTL. Our test thus represents the first integration of population genetic theory and QTL data to measure the historical influence of selection.