A variation in the structure of the protein-coding region of the human p53 gene

An extensive analysis of genomic DNA preparations from a number of normal and malignant tissues revealed BglII site polymorphism of the human p53 gene. Approximately 10% of p53 gene alleles were found to contain an additional BglII site localized in a region of intron I. This allelic form of p53 gene was also responsible for p53 protein having altered electrophoretic mobility. Molecular cloning and sequencing of both the alleles of p53 gene revealed a base-pair change in codon 72 causing arginine → proline substitution in the allele with the additional BglII site. Both variants of the p53 gene may occur in homozygous state and are therefore functional.  

Perspective: gene divergence, population divergence, and the variance in coalescence time in phylogeographic studies

Molecular methods as applied to the biogeography of single species (phylogeography) or multiple codistributed species (comparative phylogeography) have been productively and extensively used to elucidate common historical features in the diversification of the Earth's biota. However, only recently have methods for estimating population divergence times or their confidence limits while taking into account the critical effects of genetic polymorphism in ancestral species become available, and earlier methods for doing so are underutilized. We review models that address the crucial distinction between the gene divergence, the parameter that is typically recovered in molecular phylogeographic studies, and the population divergence, which is in most cases the parameter of interest and will almost always postdate the gene divergence. Assuming that population sizes of ancestral species are distributed similarly to those of extant species, we show that phylogeographic studies in vertebrates suggest that divergence of alleles in ancestral species can comprise from less than 10% to over 50% of the total divergence between sister species, suggesting that the problem of ancestral polymorphism in dating population divergence can be substantial. The variance in the number of substitutions (among loci for a given species or among species for a given gene) resulting from the stochastic nature of DNA change is generally smaller than the variance due to substitutions along allelic lines whose coalescence times vary due to genetic drift in the ancestral population. Whereas the former variance can be reduced by further DNA sequencing at a single locus, the latter cannot. Contrary to phylogeographic intuition, dating population divergence times when allelic lines have achieved reciprocal monophyly is in some ways more challenging than when allelic lines have not achieved monophyly, because in the former case critical data on ancestral population size provided by residual ancestral polymorphism is lost. In the former case differences in coalescence time between species pairs can in principle be explained entirely by differences in ancestral population size without resorting to explanations involving differences in divergence time. Furthermore, the confidence limits on population divergence times are severely underestimated when those for number of substitutions per site in the DNA sequences examined are used as a proxy. This uncertainty highlights the importance of multilocus data in estimating population divergence times; multilocus data can in principle distinguish differences in coalescence time (T) resulting from differences in population divergence time and differences in T due to differences in ancestral population sizes and will reduce the confidence limits on the estimates. We analyze the contribution of ancestral population size (theta) to T and the effect of uncertainty in theta on estimates of population divergence (tau) for single loci under reciprocal monophyly using a simple Bayesian extension of Takahata and Satta's and Yang's recent coalescent methods. The confidence limits on tau decrease when the range over which ancestral population size theta is assumed to be distributed decreases and when tau increases; they generally exclude zero when tau/(4Ne) > 1. We also apply a maximum-likelihood method to several single and multilocus data sets. With multilocus data, the criterion for excluding tau = 0 is roughly that l tau/(4Ne) > 1, where l is the number of loci. Our analyses corroborate recent suggestions that increasing the number of loci is critical to decreasing the uncertainty in estimates of population divergence time.  

On the Possibility of Constructive Neutral Evolution

The neutral theory often is presented as a theory of ``noise' or silent changes at an isolated ``molecular level,' relevant to marking the steady pace of divergence, but not to the origin of biological structure, function, or complexity. Nevertheless, precisely these issues can be addressed in neutral models, such as those elaborated here with regard to scrambled ciliate genes, gRNA-mediated RNA editing, the transition from self-splicing to spliceosomal splicing, and the retention of duplicate genes. All of these are instances of a more general scheme of ``constructive neutral evolution' that invokes biased variation, epistatic interactions, and excess capacities to account for a complex series of steps giving rise to novel structures or operations. The directional and constructive outcomes of these models are due not to neutral allele fixations per se, but to these other factors. Neutral models of this type may help to clarify the poorly understood role of nonselective factors in evolutionary innovation and directionality. Received: 3 September 1998 / Accepted: 15 February 1999  

Evolution of novel genes

Much progress in understanding the evolution of new genes has been accomplished in the past few years. Molecular mechanisms such as illegitimate recombination and LINE element mediated 3' transduction underlying exon shuffling, a major process for generating new genes, are better understood. The identification of young genes in invertebrates and vertebrates has revealed a significant role of adaptive evolution acting on initially rudimentary gene structures created as if by evolutionary tinkers. New genes in humans and our primate relatives add a new component to the understanding of genetic divergence between humans and non-humans.  

Two alleles of the single-copy chalcone synthase gene in parsley differ by a transposon-like element

We have analysed three nearly full-length cDNAs complementary to mRNAs encoding two PR1 (pathogenesis-related, class 1) proteins in parsley (Petroselinum crispum). Furthermore, one selected genomic clone containing the PcPR1-1 gene was investigated in detail. The structural organization and possible regulatory elements in the 5' flanking region of this gene are presented. In situ RNA hybridization in fungus-infected parsley leaf tissue demonstrated rapid and massive PR1 mRNA accumulation around infection sites.  

Correlations between the compositional properties of human genes,codon usage,and amino acid composition of proteins

Summary We have analyzed the correlation that exists between the GC levels of third and first or second codon position for about 1400 human coding sequences. The linear relationship that was found indicates that the large differences in GC level of third codon positions of human genes are paralleled by smaller differences in GC levels of first and second codon positions. Whereas third codon position differences correspond to very large differences in codon usage within the human genome, the first and second codon position differences correspond to smaller, yet very remarkable, differences in the amino acid composition of encoded proteins. Because GC levels of codon positions are linearly correlated with the GC levels of the isochores harboring the corresponding genes, both codon usage and amino acid composition are different for proteins encoded by genes located in isochores of different GC levels. Furthermore, we have also shown that a linear relationship with a unity slope and a correlation coefficient of 0.77 exists between GC levels of introns and exons from the 238 human genes currently available for this analysis. Introns are, however, about 5% lower in GC, on average, than exons from the same genes.