Genetic identity between populations when mutation rates vary within and across loci

A formula is derived for the probability that two genes taken at random from the same locus in two populations isolated at time t ago are of the same allelic type. The model assumed is a neutral one where there are possibly different mutation rates between different alleles. Inequalities are derived for this probability. A particular result is that for a fixed overall mutation rate, the probability is least for the infinite alleles model. Inequalities and approximations are found for Nei's genetic identity at one locus when mutation rates vary, and also for the identity across loci when the overall mutation rates per locus vary. Genetic identity at the molecular level is considered and a probability generating function found for the number of segregating sites between two randomly chosen gametes from two divergent populations, under various models.     

Allele frequencies in a multidimensional Wright-Fisher model with general mutation

A formula is obtained for the probability that two genes at a single locus, sampled at random from a population at time t, are of particular types. The model assumed is a diffusion approximation to a neutral Wright-Fisher model in which mutation is general and not necessarily symmetric. An example is given of a population in which one allele has a high mutation rate, and the others have an equal, low mutation rate. The matrix Q, with elements given by the probability of sampling two alleles of particular types, is calculated exactly and approximately for this case. A formula is given for the distribution of the number of segregating sites occurring in two randomly sampled finite sequences of completely linked sites, with general mutation at a site and identical mutation structure between sites.     

Mitochondrial DNA evolution in theDrosophila nasuta subgroup of species

Summary TheDrosophila nasuta group consists of about 12 closely related species distributed throughout the Indo-Pacific region. They are of great interest because of their evolutionary idiosyncrasies including little morphological differentiation, the ability to intercross in the laboratory often producing fertile offspring, and substantial chromosomal evolution. Studies of metric traits, reproductive isolation, and chromosomal and enzyme polymorphisms have failed to resolve the phylogeny of the species. We report the results of a survey of the mitochondrial DNA (mtDNA) restriction patterns of the species. The phylogeny obtained is consistent with other available information and suggests thatD. albomicans may represent the ancestral lineage of the group. The amount of polymorphism in local populations (=1.0% per site) is within the typical range observed in other animals, includingDrosophila. The degree of differentiation between species is, however, low: the origin of the group is tentatively dated about 6–8 million years ago. This study confirms the usefulness of mtDNA restriction patterns for ascertaining the phylogeny of closely related species.     

Selection, mutation and sexual reproduction in an infinite haploid population with a genome of finite length

We present a model which describes mutation, selection and sexual reproduction in an infinite haploid population with a finite genome. Each generation is described using an approximation which assures a certain persistent form of the distribution of the number of deleterious elements. The steady state exists and is determined. In addition, we conclude that the introduction of sexual reproduction increases the mean fitness in the equilibrium.     

On the origin and evolution of the genetic code

Two ideas have essentially been used to explain the origin of the genetic code: Crick's frozen accident and Woese's amino acid-codon specific chemical interaction. Whatever the origin and codon-amino acid correlation, it is difficult to imagine the sudden appearance of the genetic code in its present form of 64 codons coding for 20 amino acids without appealing to some evolutionary process. On the contrary, it is more reasonable to assume that it evolved from a much simpler initial state in which a few triplets were coding for each of a small number of amino acids. Analysis of genetic code through information theory and the metabolism of pyrimidine biosynthesis provide evidence that suggests that the genetic code could have begun in an RNA world with the two letters A and U grouped in eight triplets coding for seven amino acids and one stop signal. This code could have progressively evolved by making gradual use of letters G and C to end with 64 triplets coding for 20 amino acids and three stop signals. According to proposed evidence, DNA could have appeared after the four-letter structure was already achieved. In the newborn DNA world, T substituted U to get higher physicochemical and genetic stability.     

Gene algebra from a genetic code algebraic structure

By considering two important factors involved in the codon-anticodon interactions, the hydrogen bond number and the chemical type of bases, a codon array of the genetic code table as an increasing code scale of interaction energies of amino acids in proteins was obtained. Next, in order to consecutively obtain all codons from the codon AAC, a sum operation has been introduced in the set of codons. The group obtained over the set of codons is isomorphic to the group (Z₆₄, +) of the integer module 64. On the Z₆₄-algebra of the set of 64^N codon sequences of length N, gene mutations are described by means of endomorphisms f:(Z₆₄)^N→(Z₆₄)^N. Endomorphisms and automorphisms helped us describe the gene mutation pathways. For instance, 77.7% mutations in 749 HIV protease gene sequences correspond to unique diagonal endomorphisms of the wild type strain HXB2. In particular, most of the reported mutations that confer drug resistance to the HIV protease gene correspond to diagonal automorphisms of the wild type. What is more, in the human beta-globin gene a similar situation appears where most of the single codon mutations correspond to automorphisms. Hence, in the analyses of molecular evolution process on the DNA sequence set of length N, the Z₆₄-algebra will help us explain the quantitative relationships between genes.     

The structure of human mitochondrial DNA variation

Summary Restriction analysis of mitochondrial DNA (mtDNA) of 3065 humans from 62 geographic samples identified 149 haplotypes and 81 polymorphic sites. These data were used to test several aspects of the evolutionary past of the human species. A dendrogram depicting the genetic relatedness of all haplotypes shows that the native African populations have the greatest diversity and, consistent with evidence from a variety of sources, suggests an African origin for our species. The data also indicate that two individuals drawn, at random from the entire sample will differ at approximately 0.4% of their mtDNA nucleotide sites, which is somewhat higher than previous estimates. Human mtDNA also exhibits more interpopulation heterogeneity (G_ST=0.351±0.025) than does nuclear DNA (G_ST=0.12). Moreover, the virtual absence of intermediate levels of linkage disequilibrium between pairs of sites is consistent with the absence of genetic recombination and places constraints on the rate of mutation. Tests of the selective neutrality of mtDNA variation, including the Ewens-Watterson and Tajima tests, indicate a departure in the direction consistent with purifying selection, but this departure is more likely due to the rapid growth of the human population and the geographic heterogeneity of the variation. The lack of a good fit to neutrality poses problems for the estimation of times of coalescence from human mtDNA data.     

Codon swapping as a possible evolutionary mechanism

Summary It is apparent in the genetic code that amino acids of similar chemical nature have similar codons. I show how through successive codon captures (multiple rounds of Osawa-Jukes type reassignments), complete codon swappings in an unfavorable genetic code are evolutionarily feasible. This mechanisms could have complemented the ambiguity reduction and the vocabulary extension processes of codon-amino acid assignments. Evolution of wobble rules is implied. Transfer RNA molecules and synthetases may still carry memories of it.     

Study of the genetic code adaptability by means of a genetic algorithm

We used simulated evolution to study the adaptability level of the canonical genetic code. An adapted genetic algorithm (GA) searches for optimal hypothetical codes. Adaptability is measured as the average variation of the hydrophobicity that the encoded amino acids undergo when errors or mutations are present in the codons of the hypothetical codes. Different types of mutations and point mutation rates that depend on codon base number are considered in this study. Previous works have used statistical approaches based on randomly generated alternative codes or have used local search techniques to determine an optimum value. In this work, we emphasize what can be concluded from the use of simulated evolution considering the results of previous works. The GA provides more information about the difficulty of the evolution of codes, without contradicting previous studies using statistical or engineering approaches. The GA also shows that, within the coevolution theory, the third base clearly improves the adaptability of the current genetic code.     

Principal component analysis of gene frequencies and the origin of Basques

The genetic peculiarity of the Basque population has long been noted. We aim to describe Basque distinctiveness in space and assess the internal Basque heterogeneity. All these aspects are relevant to the question of the origin of Basques. After a thorough literature search, a data base was created containing all the available data on gene frequencies in the Iberian Peninsula and France. Twenty-nine systems, comprising 71 alleles, were used to carry out a principal component (PC) analysis. The results show a sharp peak in the first PC in the Basque area, which remains even when the geographic scope is widened to include western Europe. As demonstrated by “wombling” analysis, the steeper slope in the first PC is found to the east of the Basque area, along the Pyrenees. Measures of genetic heterogeneity (such as F_ST values) within the Basque country, as compared to those for non-Basques, do not show a particular internal substructuration in the Basque population. The genetic results support a scenario in which the Basques are the product of in situ differentiation around the time of the Last Glacial Maximum (18,000 B .P .), in agreement with archaeological and linguistic data. Isolation from the surrounding populations has allowed the differentiation to last for millennia, but has erased the differences existing among Basques. © 1994 Wiley-Liss, Inc.     

Compensatory evolution in diploid populations

Compensatory mutations are individually deleterious but harmless in appropriate combinations either at more than two sites within a gene or on separate genes. Considering that dominance effects of selection and heterodimer formation of gene products may affect the rate of compensatory evolution, we investigate compensatory neutral mutation models for diploid populations. Our theoretical analysis on the average time until fixation of compensatory mutations shows that these factors play an important role in reducing the fixation time of compensatory mutations if mutation rates are not low. Compensatory evolution of heterodimers is shown to occur more easily if the deleterious effects of single mutants are recessive.     

Allele frequencies of 6 autosomal STR loci in the Xibo nationality with phylogenetic structure among Chinese populations

In the present study, we investigated the genetic polymorphisms of 6 autosomal STR loci Hum-CSF1PO, D13S317, D5S818, D16S539, TH01, and TPOX in the Xibo population of Liaoning, northeastern China as well as its genetic relationships with other populations in China. No significant deviations from Hardy-Weinberg equilibrium could be found for all loci. Allele frequencies in the Xibo population ranged from 0.001 to 0.507. Among all the 6 loci, D16S539 had the highest polymorphism (PIC = 0.8632), whereas TPOX had the lowest (PIC = 0.5179). A phylogenic tree was constructed using Poptree 2 software. In the phylogenic tree, Xibo population has a distant relationship with the other populations.     

Gm and Km allotypes in four Sardinian population samples

Serum samples of 683 unrelated male and female individuals of four Sardinian population samples (Sassari, Nuoro, Oristano and Cagliari) were typed for G 1 m (1, 2, 3, 17), G 3 m (5, 6, 10, 11, 13, 14, 15, 16, 21, 26), and Km (1). Phenotype, haplotype (Gm), and allele frequencies (Km), respectively, show a remarkable variability between these four population samples. Comparisons with other Italian populations reveal the considerable genetic difference of the Sardinians, which is in particular caused by the presence of the haplotype Gm^{1, 3, 5, 10, 11, 13, 14, 26} in them. This haplotype is quite uncommon in Europeans and may reflect gene flow from Eastern populations (Phoenicians?) who came to this island in ancient-history times.     

Chaotic dynamics of allele frequencies in condition-dependent mating systems

I study the dynamics of allele frequencies in sexually reproducing populations where the choosy sex has a preference for condition-dependent displays of the opposite sex. The condition of an individual is assumed to be shaped by frequency-dependent selection. For sufficiently strong preferences the dynamics becomes increasingly complex, and periodic orbits and chaos are observed. Moreover, multiple attractors can exist simultaneously. The results hold also when the choosy sex is allowed to maintain a moderate level of assortative mating. Complex dynamics, a well studied phenomenon in a purely ecological setting, has been rarely observed in ecologically motivated population genetic models.     

Doublet frequencies and codon weighting in the DNA ofEscherichia coli and its phages

Summary A compilation of nucleic acid sequences fromE.coli and its phages has been analysed for the frequency of occurrence of nearest neighbour base doublets and codons. Several statistically significant deviations from random are found in both doublet and codon frequencies. The deviations inE.coli also appear to occur in and in the coat protein gene of MS2, whereas T4 and other parts of the MS2 genome show different sequence properties. These and other findings are discussed in relation to the hypothesis that rapidity of translation of mRNAs in theE. coli system is dependent on doublet frequency and codon usage patterns.     

Genetic structure of expanding wolf (Canis lupus) populations in Italy and Croatia,and the early steps of the recolonization of the Eastern Alps

After centuries of range contraction and demographic declines wolves are now expanding in Europe, colonizing regions from where they have been absent for centuries. Wolf colonizing the western Alps originate by the expansion of the Italian population. Vagrant wolves of Italian and Dinaric-Balkan origins have been recently observed in the Eastern Alps. In this study we compared the genetic structure of wolf populations in Italy and Croatia, aiming to identify the sources of the ongoing recolonization of the Eastern Alps. DNA samples, extracted from 282 Italian and 152 Croatian wolves, were genotyped at 12 autosomal microsatellites (STR), four Y-linked STR and at the hypervariable part of the mitochondrial DNA control-region (mtDNA CR1). Wolves in Croatia and Italy underwent recent demographic bottlenecks, but they differ in genetic diversity and population structure. Wolves in Croatia were more variable at STR loci (N_A = 7.4, H_O = 0.66, H_E = 0.72; n = 152) than wolves in Italy (N_A = 5.3, H_O = 0.57, H_E = 0.58; n = 282). We found four mitochondrial DNA (mtDNA CR1) and 11 Y-STR haplotypes in Croatian wolves, but only one mtDNA CR1 and three Y-STR haplotypes in Italy. Wolves in Croatia were subdivided into three genetically distinct subpopulations (in Dalmatia, Gorski kotar and Lika regions), while Italian wolves were not sub-structured. Assignment testing shows that the eastern and central Alps are recolonized by wolves dispersing from both the Italian and Dinaric populations. The recolonization of the Alps will predictably continue in the future and the new population will be genetically admixed and very variable with greater opportunities for local adaptations and survival.     

Initiation codon mutation as a cause of alpha thalassemia

Cloning and sequence analysis of the alpha-globin genes from a Sardinian patient with the nondeletion type of hemoglobin-H disease revealed a new type of thalassemia lesion. A mutation in the alpha 2-globin gene changes the initiation codon ATG to ACG and abolishes the function of this gene. Globin mRNA output from the affected alpha 2 locus is decreased relative to the alpha 1 locus. The mutation is detectable in genomic DNA by restriction analysis with the enzyme NcoI. Of the seven Sardinian patients with nondeletion alpha thalassemia screened with this enzyme, six had the initiation codon lesion.     

Block structure and stability of the genetic code

It is known that different codons may be unified into larger groups related to the hierarchical structure, approximate hidden symmetries, and evolutionary origin of the universal genetic code. Using a simplified evolutionary motivated two-letter version of genetic code, the general principles of the most stable coding are discussed. By the complete enumeration in such a reduced code it is strictly proved that the maximum stability with respect to point mutations and shifts in the reading frame needs the fixation of the middle letters within codons in groups with different physico-chemical properties, thus, explaining a key feature of the universal genetic code. The translational stability of the genetic code is studied by the mapping of code onto de Bruijn graph providing both the compact visual representation of mutual relationships between different codons as well as between codons and protein coding DNA sequence and a powerful tool for the investigation of stability of protein coding. Then, the results are extended to four-letter codes. As is shown, the universal genetic code obeys mainly the principles of optimal coding. These results demonstrate the hierarchical character of optimization of universal genetic code with strictly optimal coding being evolved at the earliest stages of molecular evolution. Finally, the universal genetic code is compared with the other natural variants of genetic codes.     

Evolution of fitnesses and allele frequencies in a population with spatially heterogeneous selection pressures

The level of gene flow considerably influences the outcome of evolutionary processes in structured populations with spatial heterogeneity in selection pressures; low levels of gene flow may allow local adaptation whereas high levels of gene flow may oppose this process thus preventing the stable maintenance of polymorphism. Indeed, proportions of fitness space that successfully maintain polymorphism are substantially larger in spatially heterogenous populations with lower to moderate levels of gene flow when compared to single-deme models. Nevertheless, the effect of spatial heterogeneity on the evolutionary construction of polymorphism is less clear. We have investigated the levels of polymorphism resulting from a simple two-deme construction model, which incorporates recurrent mutation as well as selection. We further compared fitness properties, stability of equilibria, and frequency distribution patterns emerging from the construction approach and compared these to the static fitness-space approach. The construction model either promotes or constrains the level of polymorphisms, depending on the levels of gene flow. Comparison of the fitness properties resulting from both approaches shows that they maintain variation in different parts of fitness space. The part of fitness space resulting from construction is more stable than that implied by the ahistoric fitness-space approach. Finally, the equilibrium allele-frequency distribution patterns vary substantially with different levels of gene flow, underlining the importance of correctly sampling spatial structure if these patterns are to be used to estimate population-genetic processes.