Structure Of Genetic Code Research Articles

The triple code model for advancing research in rare and undiagnosed diseases beyond the base pairs.

Rare and undiagnosed diseases pose significant challenges for understanding their mechanisms, diagnosis, and treatment. The Triple Code Model, an integrative paradigm described here, considers the combined influence of the genetic code, epigenetic code, and nuclear structure (an emerging code), as fundamental biochemical mechanisms underlying many rare diseases. Studies demonstrate dysfunctional membrane and cytoplasmic signals instruct the epigenome to ultimately impact the 3D structure and dynamics of the nucleus, highlighting their close interrelationships. Consequently, this model offers a holistic perspective on rare and undiagnosed diseases by moving beyond a solely genetic view. We propose that this integrated framework will efficiently guide rare disease research by taking it 'Beyond the Base Pairs,' leading to improved diagnostics and personalized treatments.

Proteome-Wide Structural Computations Provide Insights into Empirical Amino Acid Substitution Matrices

The relative contribution of mutation and selection to the amino acid substitution rates observed in empirical matrices is unclear. Herein, we present a neutral continuous fitness-stability model, inspired by the Arrhenius law (qij=aije-ΔΔGij). The model postulates that the rate of amino acid substitution (i→j) is determined by the product of a pre-exponential factor, which is influenced by the genetic code structure, and an exponential term reflecting the relative fitness of the amino acid substitutions. To assess the validity of our model, we computed changes in stability of 14,094 proteins, for which 137,073,638 in silico mutants were analyzed. These site-specific data were summarized into a 20 square matrix, whose entries, ΔΔGij, were obtained after averaging through all the sites in all the proteins. We found a significant positive correlation between these energy values and the disease-causing potential of each substitution, suggesting that the exponential term accurately summarizes the fitness effect. A remarkable observation was that amino acids that were highly destabilizing when acting as the source, tended to have little effect when acting as the destination, and vice versa (source → destination). The Arrhenius model accurately reproduced the pattern of substitution rates collected in the empirical matrices, suggesting a relevant role for the genetic code structure and a tuning role for purifying selection exerted via protein stability.

Numerical 11-Factor in Half the Genetic Code – A Search for an Explanation in Number Series

Half of 20 + 4 (double-coded) amino acids in the genetic code structure showed1 an astonishing regularity in a 2D-table, including the 11-factor. The regularities have been dismissed by professionals, saying that no known physical-chemical laws can explain them. Here a search for possible explanations or aspects is carried through by investigating the numeral series, as dimensions, of x = integers 5 → 0 with different exponents, treated in earlier papers: x3, 2x2 behind the Periodic system, x2/3 ×102 (the “ES”-series) and further the basic series with its superposed series (as coding for underlying steps) with features like quantum mechanics. The regularities are reproduced in first section. It’s shown how the paired amino acid side chains that give the 11-factor in the 2D-table are derivable in different ways through counter-directed reading of numbers in the different series (2-digit numbers that always give sums with factor 11). Introduced is the concept of step-numbers, related to numeral series, implying a vector character, with this also anti-vectors, a physical and biological reality, expressed e.g. as intervals. A main interval in the ES-series as a whole is the number 77, specially studied, the most obvious organizing principle in the 2D-table. The fact that also sums of mirrored 2-letter codons code for amino acid groups with the 11-factor points to a deeper level of double-direction acting on both levels, here suggested as inherited from the higher dimension 4D. Regarding the coding base pairs G-C and A-U as two coordinate axes, the regularities show up in amino acids with 2-letter codons that join these axes, called Mx-coded ones, the other half of the genetic code not. It seems connected with the two axes of the 2D-table and strengthens the hypothetical dimensional processes from higher to lower D-degree. Finally, factor 9 as difference of numbers read bidirectionally are circa the inversion of 11, inversion existing in physical laws. An eventual relation to centriole structure with factor 9 (×2 or ×3) of microtubules are shortly studied. This paper should be taken as material, inviting other researchers in applied physics and biochemistry to go on with the questions.

Widespread autogenous mRNA-protein interactions detected by CLIP-seq.

Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase–amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and proximity during translation), methodological (difference in CLIP protocols, peak callers and cell types) and statistical (treatment of null backgrounds). In particular, we demonstrate a high statistical significance of autogenous interactions by sampling null distributions of fixed-margin interaction matrices. Furthermore, we study the dependence of autogenous binding on the presence of RNA-binding motifs and structured domains in RBPs. Finally, we show that intrinsic nucleobase–amino acid affinities favor co-aligned binding between mRNA coding regions and the proteins they encode. Our results suggest a central role for autogenous interactions in RBP regulation and support the possibility of a fundamental connection between coding and binding.

The structure of the genetic code as an optimal graph clustering problem.

The standard genetic code (SGC) is the set of rules by which genetic information is translated into proteins, from codons, i.e. triplets of nucleotides, to amino acids. The questions about the origin and the main factor responsible for the present structure of the code are still under a hot debate. Various methodologies have been used to study the features of the code and assess the level of its potential optimality. Here, we introduced a new general approach to evaluate the quality of the genetic code structure. This methodology comes from graph theory and allows us to describe new properties of the genetic code in terms of conductance. This parameter measures the robustness of codon groups against the potential changes in translation of the protein-coding sequences generated by single nucleotide substitutions. We described the genetic code as a partition of an undirected and unweighted graph, which makes the model general and universal. Using this approach, we showed that the structure of the genetic code is a solution to the graph clustering problem. We presented and discussed the structure of the codes that are optimal according to the conductance. Despite the fact that the standard genetic code is far from being optimal according to the conductance, its structure is characterised by many codon groups reaching the minimum conductance for their size. The SGC represents most likely a local minimum in terms of errors occurring in protein-coding sequences and their translation.

Model of Genetic Code Structure Evolution under Various Types of Codon Reading

The standard genetic code (SGC) is a set of rules according to which 64 codons are assigned to 20 canonical amino acids and stop coding signal. As a consequence, the SGC is redundant because there is a greater number of codons than the number of encoded labels. This redundancy implies the existence of codons that encode the same genetic information. The size and organization of such synonymous codon blocks are important characteristics of the SGC structure whose evolution is still unclear. Therefore, we studied possible evolutionary mechanisms of the codon block structure. We conducted computer simulations assuming that coding systems at early stages of the SGC evolution were sets of ambiguous codon assignments with high entropy. We included three types of reading systems characterized by different inaccuracy and pattern of codon recognition. In contrast to the previous study, we allowed for evolution of the reading systems and their competition. The simulations performed under minimization of translational errors and reduction of coding ambiguity produced the coding system resistant to these errors. The reading system similar to that present in the SGC dominated the others very quickly. The survived system was also characterized by low entropy and possessed properties similar to that in the SGC. Our simulation show that the unambiguous SGC could emerged from a code with a lower level of ambiguity and the number of tRNAs increased during the evolution.

Models of genetic code structure evolution with variable number of coded labels

It is assumed that at the early stage of cell evolution its translation machinery was characterized by high noise, i.e. ambiguous assignment of codons to amino acids in the genetic code, which initially encoded only few amino acids. Next, during its evolution new amino acids were added to this code. Taking into account this facts, we investigated theoretical models of genetic code’s structure, which evolved from a set of ambiguous codons assignments into a coding system with a low level of uncertainty. We considered three types of translational inaccuracies assuming a different number of fixed codon positions. We applied a modified version of evolutionary algorithm for finding the genetic codes that the most effectively reduced the initial uncertainty in the assignment of codons to encoded labels, i.e. amino acids and a stop translation signal. We examined codes with the number of labels from four to 22. Our results indicated that the quality of genetic code structure is strongly dependent on the number of encoded labels as well as the type of translational mechanism. The more strict assignments of codon to the labels was preferred by the codes encoding more number of labels. The results showed that a smaller degeneracy of codes evolved from a more tolerant coding with the stepwise addition of coded amino acids to the genetic code. The distribution of codon groups in the standard genetic code corresponds well to the translation model assuming two fixed codon positions, whereas the six-codon groups can be relics form previous stages of evolution when the code characterized by a greater uncertainty.

English

Sanchez et al. (2005) have shown the structure of vector space genetic code over the Galois field GF(4) which relate to the physicochemical properties of the genetic code on proteins. From this vector space, an automorphism can be constructed to reflect the mutation process in the genetic code. This study investigates a type of transformation in the LK_ITB5a lipase gene mutation. The result of the study shows that there is a transformation matrix from the wild type gene lipase LK_ITB5a to mutant gene lipase LK_ITB5a H110F which is a diagonal matrix with non-zero determinant. This means that the transformation is an automorphism. Key words: Automorphism, vector space, mutational pathways &nbsp

Theoretical minimal RNA rings designed according to coding constraints mimic deamination gradients

Deaminations (A->G, C->T) increase with DNA singlestrandedness during replication, presumably creating spontaneous genomic mutational and nucleotide frequency gradients. Alternatively, genes are positioned to avoid deaminations. Deamination gradients affect directly mitogene third codon positions; conserved vertebrate mitochondrial tRNA and protein coding gene arrangements minimize deaminations in anticodons, and first and second codon positions in mitogenes. Here we describe deamination gradients across theoretical minimal RNA rings, 22 nucleotide-long RNAs designed to simulate prebiotic RNAs. These RNA rings code for a start/stop codon and a single codon for each amino acid, and form stem-loop hairpins slowing degradation. They resemble consensus tRNAs, defining potential anticodons and cognate amino acids. Theoretical minimal RNA rings are not designed to include deamination gradients, yet deamination gradients occur in RNA rings. tRNA homology produces stronger evidence for deamination gradients than RNA ring homology defined by coding properties. Deamination gradients start at predicted RNA ring anticodons, corresponding to known homologies between mitochondrial tRNAs and replication origins, and between bacterial tRNA synthetases and mitochondrial DNA polymerase gamma. Deamination gradients are strongest for RNA rings with predicted anticodons matching cognate amino acids that integrated early the genetic code. Presumably protections against deaminations evolved while amino acids integrated the genetic code. Results confirm tRNA-RNA ring homologies. Coding constraints defining RNA rings presumably produce deamination gradients starting at predicted anticodons. Hence, the universal genetic code determines nucleotide deamination gradients in theoretical minimal RNA rings, suggesting adaptation to prevent consequences of deamination mutations. Results also indicate that the genetic code's structure determined evolution of tRNAs, their cognates, tRNA synthetases, and polymerases.

Localized Context-Dependent Effects of the “Ambush” Hypothesis: More Off-Frame Stop Codons Downstream of Shifty Codons

The ambush hypothesis speculates that off-frame stop codons increase translational efficiency after ribosomal frameshifts by stopping early frameshifted translation. Some evidences fit this hypothesis: (1) synonymous codon usages increase with their potential contribution to off-frame stops; (2) the genetic code assigns frequent amino acids to codon families contributing to off-frame stops; (3) positive biases for off-frame stops (AT rich) occur despite adverse nucleotide (GC) biases; and (4) mitochondrial off-frame stop codon densities increase with ribosomal structural instability, potential proxy of frameshift frequencies. In this study, analyses of vertebrate mitogenes and tRNA synthetase genes from all superkingdoms and viruses test a new prediction of the ambush hypothesis: sequences immediately downstream of frameshift-inducing homopolymer codons (AAA, CCC, GGG, and TTT) are off-frame stop rich. Codons immediately downstream of homopolymer codons form more than average off-frame stops, biases are stronger than for corresponding upstream distances and for any other group of synonymous codons. Sequences downstream of that high-density region are off-frame stop depleted. This decrease suggests that off-frame stops, combined with suppressor tRNAs regulate translation of overlapping coding sequences. Results show the predictive power of the ambush hypothesis, from macroevolutionary (genetic code structure) to detailed gene sequence anatomy.

Bias for 3'-Dominant Codon Directional Asymmetry in Theoretical Minimal RNA Rings.

Aminoacyl tRNA synthetases ligate tRNAs specifically with their cognate amino acid. These synthetases are among life's earliest proteins, class II tRNA synthetases (cognates A, D, F, G, H, K, N, P, S, and T) presumably preceding class I tRNA synthetases (cognates C, E, I, L, M, Q, R, V, W, and Y). Classification of codons into palindromic (structure XYX), 5'-dominant (YXX), and 3'-dominant (XXY) (Codon Directional Asymmetry [CDA]) shows that class II tRNA synthetases aminoacylate amino acids associated with XXY. Our working hypothesis expects bias for XXY codons in primordial RNAs, such as theoretical minimal RNA rings, designed in silico to mimic life's earliest RNAs. Twenty-five RNA rings have been computed, which code over a minimal length (22 nucleotides) for a start codon, stop codon, and one and only one codon for each of the 20 amino acids, and form stem-loop hairpins preventing degradation; these 25 minimal RNAs are the only ones matching these constraints and they seem homologous to consensus tRNA sequences. This similarity defined candidate RNA ring anticodons and corresponding cognate amino acids. Here, analyses of RNA ring codon contents confirm bias for XXY codons in 13 among 14 RNA rings with unequal XXY and YXX codon numbers. This bias increases with the genetic code integration order of the RNA ring's cognate amino acid across and within tRNA synthetase classes, suggesting that evolutionary processes, and not physicochemical constraints, produced the association between CDA and tRNA synthetase classes. The self-referential hypothesis for genetic code origin, a very complete genetic code evolutionary hypothesis integrating many translational machinery components, predicts best among genetic code evolutionary hypotheses CDA biases in RNA rings. The RNA rings' simple design inadvertently reproduces CDAs predicted by the genetic code's structure, confirming theoretical minimal RNA rings as good proxies for life's earliest RNAs.

The influence of different types of translational inaccuracies on the genetic code structure

BackgroundThe standard genetic code is a recipe for assigning unambiguously 21 labels, i.e. amino acids and stop translation signal, to 64 codons. However, at early stages of the translational machinery development, the codons did not have to be read unambiguously and the early genetic codes could have contained some ambiguous assignments of codons to amino acids. Therefore, the goal of this work was to obtain the genetic code structures which could have evolved assuming different types of inaccuracy of the translational machinery starting from unambiguous assignments of codons to amino acids.ResultsWe developed a theoretical model assuming that the level of uncertainty of codon assignments can gradually decrease during the simulations. Since it is postulated that the standard code has evolved to be robust against point mutations and mistranslations, we developed three simulation scenarios assuming that such errors can influence one, two or three codon positions. The simulated codes were selected using the evolutionary algorithm methodology to decrease coding ambiguity and increase their robustness against mistranslation.ConclusionsThe results indicate that the typical codon block structure of the genetic code could have evolved to decrease the ambiguity of amino acid to codon assignments and to increase the fidelity of reading the genetic information. However, the robustness to errors was not the decisive factor that influenced the genetic code evolution because it is possible to find theoretical codes that minimize the reading errors better than the standard genetic code.

The Human Hands Model for the Essentials of the Chemistry of Life

Human hands are the model for the neon electron configuration, organic chemistry, protein function and the genetic code structure. The human hands model is investigated for the periodic table. An original genetic code table is presented for the combined vertebrate mitochondrial and universal nuclear genetic codes. The developmental connection between human (vertebrate) mitochondrial and universal (standard) nuclear genetic codes is investigated. The genetic code structure models the bones and joints structure of a human arm.

The 64-Triplet Genetic Code Structure Revisited and Refuted from Combinatorial

Statement of the problem: When molecular biologists observed in 1953 that the sequence of the DNA four bases in the nucleus of a cell influenced the sequence of the twenty amino acids of protein in the cytoplasm, they desired to find a code to account for the correlation, and eventually had the 64 triplet genetic code in 1954 from a mathematician, which is currently in use but not flawless. Methodology and theoretical orientation: The said observation is seen as a natural example of an input/output system, in which the input is the DNA four bases and the output is the sequence of 24 permutations of the four DNA bases constituting the genetic code in the cytoplasm. A combinatorial input/output multiplicative replication system armed with basic permutations computation schemes is now available to produce permutations systematically, such as Square Kinematics Scheme and Successive Collateral Posting Scheme used. Findings: A 24 quadruplet genetic code was produced by each of the two methods with an input set of the DNA four bases. It is shown in the successive collateral posting method that the 64 triplets comprise 40 non-permutations and 24 permutations. The 40 non-permutation triplets are crossed out leaving 24 permutation triplets which are undersized and therefore unqualified to represent the genetic code output sequence from an input set of 4. Conclusion and significance: The 24 quadruplet genetic code is a breakthrough in the Molecular Biologists’ search for a code following their observation which ended up with the 64-triplet genetic code that has no combinatorially valid code word being triplets, instead of quadruplets. Recommendations: These are made towards effective publicity of the new 24 quadruplet genetic code to attract experimental experts to spell it to win adoption in coding application in protein studies for a desired relief to stakeholders in genetics.

The role of crossover operator in evolutionary-based approach to the problem of genetic code optimization

One of theories explaining the present structure of canonical genetic code assumes that it was optimized to minimize harmful effects of amino acid replacements resulting from nucleotide substitutions and translational errors. A way to testify this concept is to find the optimal code under given criteria and compare it with the canonical genetic code. Unfortunately, the huge number of possible alternatives makes it impossible to find the optimal code using exhaustive methods in sensible time. Therefore, heuristic methods should be applied to search the space of possible solutions. Evolutionary algorithms (EA) seem to be ones of such promising approaches. This class of methods is founded both on mutation and crossover operators, which are responsible for creating and maintaining the diversity of candidate solutions. These operators possess dissimilar characteristics and consequently play different roles in the process of finding the best solutions under given criteria. Therefore, the effective searching for the potential solutions can be improved by applying both of them, especially when these operators are devised specifically for a given problem. To study this subject, we analyze the effectiveness of algorithms for various combinations of mutation and crossover probabilities under three models of the genetic code assuming different restrictions on its structure. To achieve that, we adapt the position based crossover operator for the most restricted model and develop a new type of crossover operator for the more general models. The applied fitness function describes costs of amino acid replacement regarding their polarity. Our results indicate that the usage of crossover operators can significantly improve the quality of the solutions. Moreover, the simulations with the crossover operator optimize the fitness function in the smaller number of generations than simulations without this operator. The optimal genetic codes without restrictions on their structure minimize the costs about 2.7 times better than the canonical genetic code. Interestingly, the optimal codes are dominated by amino acids characterized by polarity close to its average value for all amino acids.

Secrets of the genetic code: A view of a mathematician

On the basis of studying genes, new properties of the genetic code were established and its major integrated characteristics were calculated. Two groups of such characteristics were distinguished. The first group deals with the integrated characteristics for the DNA regions where genes overlap pairwise, and all five cases of the overlappings allowed by DNA structure were investigated. The second group of characteristics deals with the most extended DNA regions without genetic overlappings. The interrelation of the established integrated characteristics in the two groups was established. As a result, several previously unknown effects were found. Two functions were revealed in which all reassigned codons in mitochondrial genetic codes (of humans and other organisms) are involved, and the fundamental distinctions in the integrated characteristics of such codes from the standard ones were revealed. Other properties of the genetic code structure following from the obtained results were also established.

The Logic of Self-Organized Criticality

Abstract A consideration of non-classical logic in terms of classical one allows us to show a role of designated truth values. In this way we show that our version of non-classical many-valued logic can be based on the structure of genetic code.

The Origin of the Genetic Code: Matter of Metabolism or Physicochemical Determinism?

In the research field on the origin of the genetic code two lines of thought are evident. The first puts at the core of the origin of the genetic code the physicochemical properties of amino acids (1967; Woese et al. 1966; Jungck 1978; Weber and Lacey 1978; Lacey and Mullins 1983; Di Giulio 1989a, b; Taylor and Coates 1989; Di Giulio 1996; Freeland and Hurst 1998; Lacey et al. 1992). Indeed, the physicochemical theory of the origin of the genetic code suggests that these properties have been the main selective pressure that determined the organisation of the genetic code (Sonneborn 1965; Woese et al. 1966; Fitch and Upper 1987; Di Giulio 1997). A prediction in part equivalent is also made by the stereochemical theory of the origin of the genetic code that maintains that interactions between codons or anticodons and amino acids have been the main forces that organised the genetic code (Woese 1967; Shimizu 1982; Szathmary 1993; Yarus 1998; Yarus et al. 2009). Therefore, also for the stereochemical hypothesis the physicochemical properties of amino acids were essential in organising the code. On the other hand, the second line of thought considers the metabolism and the biosynthetic relationships between amino acids as the main force that defined the evolutionary organisation of the genetic code (Wong 1975, 2005; Di Giulio 2008a), with the properties of amino acids having only a subsidiary role in this organisation (Wong 1980; Di Giulio 1989a). The current special issue of the Journal of Molecular Evolution, dedicated to the Evolution of the Genetic Code, presents four papers that summarise this field of study at the moment and bring some insight into these two lines of thought. Naturally, whether the physicochemical properties of amino acids would reflect the structure of proteins, that is to say their function, then this would not be incompatible with the coevolution theory of the genetic code, because the protein structure, by means of the physicochemical properties of amino acids, might have been the main selective pressure that determined the genetic code organisation. Obviously, this would also imply a correlation between the biosynthetic relationships of amino acids and their physicochemical properties, in addition to that with the structure of the genetic code, as some works seem to indicate (Di Giulio 1991, 1996). One of the works presented in this special issue by Francis (2013) is inclined to maintain a similar position. Indeed, the title of this paper is: ‘Evolution of the genetic code by incorporation of amino acids that improved or changed protein function’. Furthermore, Francis (2013) considers the hypothesis that very early on the genetic code used only codons of the GNC kind (Ikehara 2002; Trifonov 2004; Francis 2011), a code completely compatible also with the coevolution theory (Di Giulio 2008a). However, the observation that the properties of amino acids are mirrored in the genetic code organisation does not necessarily imply their determining role in the genetic code organisation, unless one does not validate that the level reached by the minimisation of physicochemical distances between amino acids in the genetic code structure is very elevated. This, at the moment, does not seem to be the case (Wong 1980; Di Giulio 1989a; Di Giulio et al. 1994; Di M. Di Giulio (&) Laboratory for Molecular Evolution, Institute of Genetics and Biophysics ‘Adriano Buzzati Traverso’, CNR, Via P. Castellino, 111, 80131 Naples, Napoli, Italy e-mail: massimo.digiulio@igb.cnr.it; digiulio@igb.cnr.it

The Socionatural Engineering of Reductionist Metaphors: A Political Ecology of Synthetic Biology

Political ecologists and biomedical anthropologists influenced by science and technology studies view genes as socionatural articulation points, or boundary objects, in the reshaping of societies, natures, and economies. Many of these scholars portray genetic technology as a tool for producing a new class of commodities. Scientists working for biotechnology corporations, they argue, mobilize the reductive metaphor that genes are information or code. They do this to stabilize genes for trade and ownership. Social scientists note that social negotiations involved in this reductive work, along with contingencies in the biological functioning of genes, limit and pattern how genetic material can be commodified. In this paper I critically review and extend these empirical analyses with attention to how current legal battles are redefining how genes can be owned. I then identify places where political ecologists can contribute to detailing the social, legal, and biological mutations motivated by the commodification of genes. This attention is crucial as traditional genetic technologies are being replaced by synthetic biology. Synthetic biology is a set of scientific practices that attempt to actualize the reductive informational code metaphor. Synthetic biologists seek to strip genes and organisms of their unpredictable behaviors by building organisms from the ground up, according to engineering design principles. By detailing synthetic biologists' attempts to reengineer both the structure of genetic code, and the cellular systems that give this code material expression, I first argue that synthetic technologies are producing standardized organisms and molecular parts that are extremely conducive to commodification. Additionally, I assert that the sociotechnical strategies employed by synthetic biologists to find and create useful genetic material intentionally avoid ambiguities in gene-ownership regimes as they are currently constituted. Finally, I examine situations where political ecologists can contribute to the critical analysis and transformation of synthetic biology's social and technical terrains.

Comparison of period-3 correlation amplitudes in genomic DNA sequences

Period-3 oscillations in genome composition can be detected through correlation functions. Since these oscillations are closely related to the genetic code structure, we developed methods for quantitative comparison of genomic and exonic oscillation amplitudes and decay. In contrast to genomic correlations, exonic period-3 oscillation amplitudes are persistent. A model postulating an uncorrelated distribution of exons in the genome has been applied to the analysis of Escherichia coli K12, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens genomic decay, allowing for a quantitative discussion of genome organization.