An Analysis of the Metabolic Theory of the Origin of the Genetic Code

A computer program was used to test Wong's coevolution theory of the genetic code. The codon correlations between the codons of biosynthetically related amino acids in the universal genetic code and in randomly generated genetic codes were compared. It was determined that many codon correlations are also present within random genetic codes and that among the random codes there are always several which have many more correlations than that found in the universal code. Although the number of correlations depends on the choice of biosynthetically related amino acids, the probability of choosing a random genetic code with the same or greater number of codon correlations as the universal genetic code was found to vary from 0.1% to 34% (with respect to a fairly complete listing of related amino acids). Thus, Wong's theory that the genetic code arose by coevolution with the biosynthetic pathways of amino acids, based on codon correlations between biosynthetically related amino acids, is statistical in nature. Received: 8 August 1996 / Accepted: 26 December 1996     

Genetic drift and the population history of the Irish travellers

The Irish Travellers are an itinerant group in Ireland that has been socially isolated. Two hypotheses have been proposed concerning the genetic origin of the Travellers: (1) they are genetically related to Roma populations in Europe that share a nomadic lifestyle or (2) they are of Irish origin, and genetic differences from the rest of Ireland reflect genetic drift. These hypotheses were tested using data on 33 alleles from 12 red blood cell polymorphism loci. Comparison with other European, Roma, and Indian populations shows that the Travellers are genetically distinct from the Roma and Indian populations and most genetically similar to Ireland, in agreement with earlier genetic analyses of the Travellers. However, the Travellers are still genetically distinct from other Irish populations, which could reflect some external gene flow and/or the action of genetic drift in a small group that was descended from a small number of founders. In order to test the drift hypothesis, we analyzed genetic distances comparing the Travellers to four geographic regions in Ireland. These distances were then compared with adjusted distances that account for differential genetic drift using a method developed by Relethford (Hum Biol 68 ( 1996 ) 29–44). The unadjusted distances show the genetic distinctiveness of the Travellers. After adjustment for the expected effects of genetic drift, the Travellers are equidistant from the other Irish samples, showing their Irish origins and population history. The observed genetic differences are thus a reflection of genetic drift, and there is no evidence of any external gene flow. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Unravelling the effects of contemporary and historical range expansion on the distribution of genetic diversity in the damselfly Coenagrion scitulum

Although genetic diversity provides the basic substrate for evolution, there are a limited number of studies that assess the impact of recent climate change on intraspecific genetic variation. This study aims to unravel the degree to which historical and contemporary factors shape genetic diversity and structure across a large part of the range of the range‐expanding damselfly Coenagrion scitulum (Rambur, 1842). A total of 525 individuals from 31 populations were genotyped at nine microsatellites, and a subset was sequenced at two mitochondrial genes. We inferred the importance of geography, environmental factors, and recent range expansion on genetic diversity and structure. Genetic diversity decreased going westwards, suggesting a signature of historical post‐glacial expansion from east to west and the presence of eastern refugia. Although genetic differentiation decreased going northwards, it increased in the northern edge populations, suggesting a role of contemporary range expansion on the genetic make‐up of populations. The phylogeographical context was proven to be essential in understanding and identifying the genetic signatures of local contemporary processes. Within this framework, our results highlight that recent range expansion of a good disperser can decrease genetic diversity and increase genetic differentiation which should be considered when devising suitable conservation strategies.     

Living on the edge: the role of geography and environment in structuring genetic variation in the southernmost populations of a tropical oak

Understanding the factors determining genetic diversity and structure in peripheral populations is a long‐standing goal of evolutionary biogeography, yet little empirical information is available for tropical species. In this study, we combine information from nuclear microsatellite markers and niche modelling to analyse the factors structuring genetic variation across the southernmost populations of the tropical oak Quercus segoviensis. First, we tested the hypothesis that genetic variability decreases with population isolation and increases with local habitat suitability and stability since the Last Glacial Maximum (LGM). Second, we employed a recently developed multiple matrix regression with randomisation (MMRR) approach to study the factors associated with genetic divergence among the studied populations and test the relative contribution of environmental and geographic isolation to contemporary patterns of genetic differentiation. We found that genetic diversity was negatively correlated with average genetic differentiation with other populations, indicating that isolation and limited gene flow have contributed to erode genetic variability in some populations. Considering the relatively small size of the study area (<120 km), analyses of genetic structure indicate a remarkable inter‐population genetic differentiation. Environmental dissimilarity and differences in current and past climate niche suitability and their additive effects were not associated with genetic differentiation after controlling for geographic distance, indicating that local climate does not contribute to explain spatial patterns of genetic structure. Overall, our data indicate that geographic isolation, but not current or past climate, is the main factor determining contemporary patterns of genetic diversity and structure within the southernmost peripheral populations of this tropical oak.     

The mystery of the mystery of common genetic diseases

Common monogenic genetic diseases, ones that have unexpectedly high frequencies in certain populations, have attracted a great number of conflicting evolutionary explanations. This paper will attempt to explain the mystery of why two particularly extensively studied common genetic diseases, Tay Sachs disease and cystic fibrosis, remain evolutionary mysteries despite decades of research. I review the most commonly cited evolutionary processes used to explain common genetic diseases: reproductive compensation, random genetic drift (in the context of founder effect), and especially heterozygote advantage. The latter process has drawn a particularly large amount of attention, having so successfully explained the elevated frequency of sickle cell anemia in malaria-endemic areas. However, the empirical evidence for heterozygote advantage in other common genetic diseases is quite weak. I introduce and illustrate the significance of a hierarchy of genetic disease phenomena found within the genetic disease explanations, which include the phenomena: single mutation variants of a common genetic disease, single genetic diseases, and classes of diseases with related phenotypic effects. I demonstrate that some of the confusion over the explanations of common genetic diseases can be traced back to confusions over which phenomena are being explained. I proceed to briefly evaluate the existing evidence for two common human genetic diseases: Tay Sachs disease and cystic fibrosis. The above considerations will ultimately shed light on why these diseases’ evolutionary explanations remain so deeply unresolved after so such a great volume of research.     

Exploring the role of Micronesian islands in the maintenance of coral genetic diversity in the Pacific Ocean

Understanding how genetic diversity is maintained across patchy marine environments remains a fundamental problem in marine biology. The Coral Triangle, located in the Indo‐West Pacific, is the centre of marine biodiversity and has been proposed as an important source of genetic diversity for remote Pacific reefs. Several studies highlight Micronesia, a scattering of hundreds of small islands situated within the North Equatorial Counter Current, as a potentially important migration corridor. To test this hypothesis, we characterized the population genetic structure of two ecologically important congeneric species of reef‐building corals across greater Micronesia, from Palau to the Marshall Islands. Genetic divergences between islands followed an isolation‐by‐distance pattern, with Acropora hyacinthus exhibiting greater genetic divergences than A. digitifera, suggesting different migration capabilities or different effective population sizes for these closely related species. We inferred dispersal distance using a biophysical larval transport model, which explained an additional 15–21% of the observed genetic variation compared to between‐island geographical distance alone. For both species, genetic divergence accumulates and genetic diversity diminishes with distance from the Coral Triangle, supporting the hypothesis that Micronesian islands act as important stepping stones connecting the central Pacific with the species‐rich Coral Triangle. However, for A. hyacinthus, the species with lower genetic connectivity, immigration from the subequatorial Pacific begins to play a larger role in shaping diversity than input from the Coral Triangle. This work highlights the enormous dispersal potential of broadcast‐spawning corals and identifies the biological and physical drivers that influence coral genetic diversity on a regional scale.     

Dissection of the genetic architecture of body weight in chicken reveals the impact of epistasis on domestication traits

In this contribution, we study the genetic mechanisms leading to differences in the observed growth patterns of domesticated White Leghorn chickens and their wild ancestor the red jungle fowl. An epistatic QTL analysis for several body-weight measures from hatch to adulthood confirms earlier findings that polymorphisms at >15 loci contribute to body-weight determination in an F(2) intercross between these populations and that many loci are involved in complex genetic interactions. Here, we use a new genetic model to decompose the genetic effects of this multilocus epistatic genetic network. The results show how the functional modeling of genetic effects provides new insights into how genetic interactions in a large set of loci jointly contribute to phenotypic expression. By exploring the functional effects of QTL alleles, we show that some alleles can display temporal shifts in the expression of genetic effects due to their dependencies on the genetic background. Our results demonstrate that the effects of many genes are dependent on genetic interactions with other loci and how their involvement in the domestication process relies on these interactions.     

New approaches to assessing the effects of mutagenic agents on the integrity of the human genome

Heritable genetic alterations, although individually rare, have a substantial collective health impact. Approximately 20% of these are new mutations of unknown cause. Assessment of the effect of exposures to DNA damaging agents, i.e. mutagenic chemicals and radiations, on the integrity of the human genome and on the occurrence of genetic disease remains a daunting challenge. Recent insights may explain why previous examination of human exposures to ionizing radiation, as in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New opportunities to assess the heritable genetic damaging effects of environmental mutagens are afforded by: (1) integration of knowledge on the molecular nature of genetic disorders and the molecular effects of mutagens; (2) the development of more practical assays for germline mutagenesis; (3) the likely use of population-based genetic screening in personalized medicine.     

Multiple geographic origins and high genetic differentiation of the Alpine marmots reintroduced in the Pyrenees

Reintroductions inherently involve a small number of founders leading reintroduced populations to be prone to genetic drift and, consequently, to inbreeding depression. Assessing the origins as the genetic diversity and structure of reintroduced populations compared to native populations are thus crucial to foresee their future. Here, we aim to clarify the origins of the Alpine marmots reintroduced in the Pyrenees and to evaluate the genetic consequences of this reintroduction after almost 30 years without monitoring. We search for the origins and compare the genetic structure and the genetic variability of three reintroduced Pyrenean and eight native Alpine populations using pairwise genetic distances, Bayesian clustering method and multivariate analyses. Our results reveal that the Alpine marmots reintroduced in the Pyrenees originated both from the Northern and the Southern Alps, and that, despite these multiple origins, none of the current Pyrenean marmots are admixed. The reintroduction led to a strong genetic differentiation and to a decrease in genetic diversity. This pattern likely results from the small number of founders and the low dispersal capacities of Alpine marmots and thus, highlight the necessity to consider both genetic characteristics and natural history when reintroducing a species.     

Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyse the morphological diversification of the Monodelphis brevicaudata species group. We found that within‐species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between‐species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation.     

Mitochondrial genetics in perspective: the derivation of a genetic and physical map of the yeast mitochondrial genome.

The attainment of the map of functions coded in the yeast mitochondrial genome represents the end of an era of development in mitochondrial genetics. Following the earliest genetic studies, where first the respiration-deficient petite mutants, then subsequently the other types of mitochondrial mutants, were characterized, it was realized that a genetic approach to the questions of mitochondrial biogenesis and the genetic function of mtDNA would yield much useful information. A period of intensive investigation into the behavior of mitochondrial genes in genetic crosses followed, and it was concluded that the purely genetic techniques of transmissional and recombinational analysis could not yield a map of the genetic loci, although basic rules for mitochondrial genetic manipulation were established. The concurrent studies of the nature of the deletions in petite mtDNA led to the recognition that an analysis of the behavior of genetic loci in petite mutants would provide the method for genetically mapping the positions of loci in mtDNA where conventional genetic crosses between grande strains had failed. This thesis was first confirmed by our studies of the frequencies of coretention and loss of individual loci in large populations of petite isolates, which produced the first circular genetic map of drug resistance loci on mtDNA. Subsequent to this genetic mapping phase, we established a general procedure for determining the physical map position of any mitochondrial genetic locus or mtDNA sequence by introducing the use of a molecular library of petite mutants carrying physically and genetically defined segments of mtDNA. These petites can be tested for the retention or loss of genetic loci or particular nucleotide sequences. This general solution to the mapping problem and the physical map of the Saccharomyces cerevisiae mitochondrial genome obtained, which has been confirmed by studies using restriction enzymes, has provided the field with a molecular point of reference for the many current genetic and biochemical investigations into the structure and function of mtDNA in yeast.     

Critical roles for a genetic code alteration in the evolution of the genus Candida

During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross-protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.     

The Level and Landscape of Optimization in the Origin of the Genetic Code

We consider a model of the origin of genetic code organization incorporating the biosynthetic relationships between amino acids and their physicochemical properties. We study the behavior of the genetic code in the set of codes subject both to biosynthetic constraints and to the constraint that the biosynthetic classes of amino acids must occupy only their own codon domain, as observed in the genetic code. Therefore, this set contains the smallest number of elements ever analyzed in similar studies. Under these conditions and if, as predicted by physicochemical postulates, the amino acid properties played a fundamental role in genetic code organization, it can be expected that the code must display an extremely high level of optimization. This prediction is not supported by our analysis, which indicates, for instance, a minimization percentage of only 80%. These observations can therefore be more easily explained by the coevolution theory of genetic code origin, which postulates a role that is important but not fundamental for the amino acid properties in the structuring of the code. We have also investigated the shape of the optimization landscape that might have arisen during genetic code origin. Here, too, the results seem to favor the coevolution theory because, for instance, the fact that only a few amino acid exchanges would have been sufficient to transform the genetic code (which is not a local minimum) into a much better optimized code, and that such exchanges did not actually take place, seems to suggest that, for instance, the reduction of translation errors was not the main adaptive theme structuring the genetic code.     

Genetics of Mandible Form in the Mouse

The underlying determination of phenotypic variability and covariability is described for 14 traits that define the morphological size and shape of the mature mouse mandible. Variability is partitioned into components due to direct additive and dominance genetic effects, indirect maternal additive genetic effects, genetic covariance between direct additive and indirect maternal additive effects and common and residual environmental effects. Multivariate analyses of the dimensionality of genetic variability indicate several complex and independent genetic components underlie the morphological form of the mandible. The multidimensional nature of the genetic components suggests a complex picture with regard to the consequences of selection on mandibular form.     

Study of interaction of wild soybean subpopulations (Glycine soja) in the valley of the Tsukanovka river in the south of Far East of Russia

A comparative study of the genetic structure of natural and anthropogenic populations of G. soja gives significant information about formation of different populations, and allows developing measures for preservation of unique natural gene bank of wild soybean, the species closely related to cultivated soybean. In this study, ISSR markers were used to carry out a comparative analysis of genetic structure of natural and anthropogenic subpopulations of G. soja for studying possible mutual influence of subpopulations of anthropogenic and natural phytocenosis on the formation of their genetic diversity and to study genetic structure of natural subpopulations of wild soybean in the contact places between the two types ofcenoses. As a result, the characteristics that describe the genetic diversity of studied populations have been identified and the important role of an interaction between subpopulations of different phytocenoses on formation of the spatial genetic structure of population in the valley of Tsukanovka river has been demonstrated.     

Genetic structure of brown trout, salmo trutta l., at the southern limit of the distribution range of the anadromous form

Genetic variation at 33 protein loci was investigated in 41 wild brown trout populations from four river basins in Galicia (northwest Spain) to analyse the amount and distribution of genetic diversity in a marginal area, located in the distribution limit of the anadromous form of this species. The genetic diversity detected within populations (H between 0 and 6%) lies within the range quoted for this species in previous reports. The Mino, the most southern river basin analysed, showed a significantly lower genetic diversity and the highest genetic differentiation among the river basins studied. The hierarchical gene diversity analysis showed high population differentiation in a restricted area (GST = 27%), mostly due to differences among populations within basins (GSC = 22%). The reduction of GST observed when the isolated samples were excluded from the analysis (GST = 17%) showed the importance of habitat fragmentation on the heterogeneity detected. Gene flow among populations was comparatively evaluated by three indirect methods, which in general revealed low figures of absolute number of migrants per generation, slightly higher than 1. The gene flow among basins reflected a positive relationship with geographical distance. This trend was confirmed by the significant correlation observed between geographical and genetic distances, including all population pairs, which suggests a component of isolation by distance in brown trout genetic structure. Nevertheless, the nonsignificant intrabasin correlation demonstrates the complexity of genetic relationships among populations in this species. The model of genetic structure in brown trout is discussed in the light of the results obtained.     

Genetic support groups in the delivery of comprehensive genetic services.

This research sought information about the services provided by genetic support groups, their members' experiences in obtaining genetic and related services, and members' recommendations for improving services. Results from a survey of 43 directors of genetic support groups showed that these organizations not only provide their members with a wide range of informational and supportive services but also address the need for education of both the public and health professionals about genetic disorders. A second survey of 931 members of genetic support groups found that, although they obtained genetic information from a variety of professional and informal sources, many of them experienced barriers to obtaining sufficient genetic information. Respondents called for professionals to improve their interpersonal skills in working with clients and to assist families in obtaining a wider variety of services. On the basis of these findings, a service model and priorities are proposed to bring together genetic specialists, community professionals, and genetic support groups for the delivery of comprehensive services to individuals and families with genetic disorders.     

Testing the "malaria hypothesis" for the case of Thailand: a genetic appraisal

This study provides statistical analyses of allele frequencies for populations of Thailand, with an attempt to trace the roles of differential malarial selection and genetic admixtures on the observed frequency variation of certain red cell genetic abnormalities (the two beta-globin variants--hemoglobin E and beta-thalassemia--and G-6PD deficiency), probably evolving under malarial endemicity. It is found that frequencies of hemoglobin E vary accordingly with those of G-6PD deficiency, and with diverse malarial ecology. The levels of genetic diversity are greater for hemoglobin E and G-6PD deficiency than for most other nonmalarial related genetic markers, suggesting the evolution of these two genetic abnormalities under differential selection. Results of the Mantel's statistical test for correspondence between distance matrices suggest distinctive patterns of allele frequency differentiation between malarial-related and nonmalarial-related genetic loci. Correlations between beta-globin and G-6PD genetic distances, as well as those between both sets of distances and the malarial distances, are statistically significant. On the other hand, a correlation between malarial distances and the genetic distances for nonmalarial-related genetic loci is not significant statistically. A correlation between the beta-globin genetic distances and the genetic distances for nonmalarial-related genetic loci is, however, statistically significant. The latter result could be attributed largely to the clustering of relatively high hemoglobin E frequencies among genetically closely related populations of northeastern Thailand, whose recent homeland was Laos. The consistently low frequencies of beta-thalassemia observed in most studied populations are explained as a result of the replacement of this genetic variant by hemoglobin E, under long-term malarial selection.     

Analysis of the Genetic Demographic Structure of Rural Populations Neighboring the Semipalatinsk Nuclear Test Site

Rural populations neighboring the Semipalatinsk nuclear test site were used as a model to develop and test an integrated population-genetic approach to analysis of the medical genetic situation and environmental conditions in the areas studied. The contributions of individual factors of population dynamics into the formation of the genetic load were also assessed. The informative values of some genetic markers were estimated. Based on these estimates, a mathematical model was constructed that makes it possible to calculate numerical scores for analysis of the genetic loads in populations differing in environmental exposure.     

Ethnic genetics: ethnogeographic diversity of the gene pool of human populations around the world]

The study was undertaken to estimate a degree of genetic differentiation in human all-world population at the ethnic level of its structure. The genetic information for this work came from well-known A. Mourant's et al. world-wide survey on human genetic polymorphisms and from regional survey on the same polymorphisms of the USSR peoples. The data were grouped into 9 regional populations studied for 49 alleles and haplotypes belonging to 20 polymorphic loci. Average genetic distances from the all-world human gene pool to each of regional one, and from these to gene pools of ethnic groups within regions were estimated and compared. An unexpected result of this within-between-region comparative analysis is the shortest genetic distance between gene pools of the USSR peoples as a whole on the one hand, and all-world peoples on the other. At the same time, a considerable part of the total human genetic polymorphism is persisted in the USSR region.