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E Zuckerkandl

Publications and source records attributed to E Zuckerkandl.

At least 19 recordsLinked to original sources
PubMed1997

Neutral and nonneutral mutations: the creative mix--evolution of complexity in gene interaction systems.

Random drift, while indifferent to the functionality of the molecular features on which it acts, may nevertheless affect evolving molecular mechanisms. It can lead to functional novelty in either gene structure or regulation. In particular, a nearly neutral (in the sense of Ohta), somewhat deleterious mutation can result in a loss of efficiency in gene regulation, and this loss is expected at times to be compensated by a selected event of a particular type: the use of an additional regulatory factor. An accumulation of additional regulatory factors, implying a combination of events of drift and selection, can permit regulatory systems to achieve an increase in both specificity and complexity as mere byproducts of a particular repair process. Nearly neutral mutations thus may, at times, constitute a required pathway for increases in gene interaction complexity. The process seems to point to an inbuilt drive-built into the gene interaction system itself-toward the evolution of higher organisms. This is a matter worthy of experimental exploration, since the general foundations for the evolution of "higher" from "lower" organisms seems so far to have largely eluded analysis.

Animals↗
PubMed1995

Tracking heterochromatin.

The Second International Workshop on Drosophila Heterochromatin, held in Honolulu from January 4-7, 1995, brought together about 70 scientists from the US, Canada, Germany, Italy, Russia, and the Netherlands. After the first of these international meetings, five years ago, Mary Lou Pardue and Wolfgang Hennig, in these columns, commented on its proceedings, and on heterochromatin in general. Although the questions that they raised cannot yet be answered exhaustively, important and sometimes surprising new observations have been made, some previously tentative answers have been firmed up, and some theoretical views underwent significant shifts. We wish to reflect here a few of the data presented at the second workshop, and express some thoughts suggested to us by these recent findings.

Animals↗
PubMed1994

Molecular pathways to parallel evolution: I. Gene nexuses and their morphological correlates.

Aspects of the regulatory interactions among genes are probably as old as most genes are themselves. Correspondingly, similar predispositions to changes in such interactions must have existed for long evolutionary periods. Features of the structure and the evolution of the system of gene regulation furnish the background necessary for a molecular understanding of parallel evolution. Patently "unrelated" organs, such as the fat body of a fly and the liver of a mammal, can exhibit fractional homology, a fraction expected to become subject to quantitation. This also seems to hold for different organs in the same organism, such as wings and legs of a fly. In informational macromolecules, on the other hand, homology is indeed all or none. In the quite different case of organs, analogy is expected usually to represent attenuated homology. Many instances of putative convergence are likely to turn out to be predominantly parallel evolution, presumably including the case of the vertebrate and cephalopod eyes. Homology in morphological features reflects a similarity in networks of active genes. Similar nexuses of active genes can be established in cells of different embryological origins. Thus, parallel development can be considered a counterpart to parallel evolution. Specific macromolecular interactions leading to the regulation of the c-fos gene are given as an example of a "controller node" defined as a regulatory unit. Quantitative changes in gene control are distinguished from relational changes, and frequent parallelism in quantitative changes is noted in Drosophila enzymes. Evolutionary reversions in quantitative gene expression are also expected. The evolution of relational patterns is attributed to several distinct mechanisms, notably the shuffling of protein domains. The growth of such patterns may in part be brought about by a particular process of compensation for "controller gene diseases," a process that would spontaneously tend to lead to increased regulatory and organismal complexity. Despite the inferred increase in gene interaction complexity, whose course over evolutionary time is unknown, the number of homology groups for the functional and structural protein units designated as domains has probably remained rather constant, even as, in some of its branches, evolution moved toward "higher" organisms. In connection with this process, the question is raised of parallel evolution within the purview of activating and repressing master switches and in regard to the number of levels into which the hierarchies of genic master switches will eventually be resolved.

Animals↗
PubMed1992

Revisiting junk DNA.

The distribution of functions within genomes of higher organisms relative to processes that lead to the spread of mutations in populations is examined in its general outlines. A number of points are enumerated that collectively put in question the concept of junk DNA: the plausible compatibility of DNA function with rapid substitution rates; the likelihood of superimposed functions along much of eukaryotic DNA; the potential for a merely conditional functionality in sequence repeats; the apparent adoption of macromolecular waste as a strategy for maintaining a function without selective grooming of individual sequence repeats that carry out the function; the likely requirement that any DNA sequence must be "polite" vis-'a-vis (compatible with) functional sequences in its genomic environment; the existence in germ-cell lineages of selective constraints that are not apparent in populations of individuals; and the fact that DNA techtonics - the appearance and disappearance of genomic DNA - are not incompatible with function. It is pointed out that the inverse correlation between functional constraints and rates of substitution cannot be claimed to be pillar of the neutral theory, because it is also predicted from a selectionist viewpoint. The dispensability of functional structures is brought into relation with the concept of reproductive sufficiency the survivability of genotypes in the absence of fitter alleles.

Animals↗
PubMed1991

Free left arms as precursor molecules in the evolution of Alu sequences.

The dimeric Alu molecule of human and other primates is composed of a left and a right arm that are very similar but show characteristic differences. If the Alu sequence has arisen through the fusion of monomeric precursor molecules, the traces of such precursor genes are expected still to be present in contemporary primate DNA. We report finding seven independent human DNA sequences that qualify as descendants of a left-arm precursor gene. Some characteristics in primary and secondary structures of these sequences are described.

Animals↗
PubMed1991

Quantitative protein changes in metastatic versus primary epithelial ovarian carcinoma.

Primary and metastatic ovarian carcinomas from six patients were obtained during primary exploratory laparotomy. Tumor cells were synthetically radiolabeled with [35S]methionine. Radiolabeled cellular proteins of the primary and metastatic cells were examined by two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. Computer assisted analysis of the resultant autoradiograms revealed that the amounts of only two proteins, p35 and p36, were consistently and significantly decreased in the metastatic tumor cells. No other consistent differences in protein synthesis between primary and metastatic tumors were detected.

Down-Regulation↗
PubMed1989

Maintenance of function without selection: Alu sequences as "cheap genes".

Continued insertion into the genome of functional Alu sequences is expected to compensate for the functional eclipse of older sequences attributable to structural adulteration and can be presumed to establish a renewable store of functional sequences at a relatively elevated numerical level. This store of functional sequences could be maintained at almost no selective cost. A strategy of maintaining function in multiple sequence copies with selection limited to a very few master (source) sequences may be resorted to also by other types of DNA sequences that are generated repeatedly during evolution and that are spread over many sectors of the genome.

Animals↗
PubMed1988

Generation of high specificity of effect through low-specificity binding of proteins to DNA.

It is proposed that proteins can bind with relatively low-affinity and specificity to multiple sites, defined as sequence motifs, on polynucleotide chains, and that such binding can collectively be turned into high-affinity, high-specificity binding through cooperative effects, especially when the sequence motifs recur periodically. The selection of individual nucleotides has in general been thought to be the condition of the existence and conservation of function in most of the noncoding sequences. This condition seems unnecessary. Calculations are presented as a step in the direction of giving credibility to a model of stable gene repression.

DNA↗
PubMed1988

Concentration-affinity equivalence in gene regulation: convergence of genetic and environmental effects.

It is proposed that equivalent phenotypic effects can be obtained by either structural changes in macromolecules involved in gene regulation or changes in activity of the structurally unaltered macromolecules. This equivalence between changes in activity (concentration) and changes in structure can come into play within physiologically plausible limits and seems to represent an important interface between environment and genome--namely, between environmentally determined and genetically determined gene expression. The equivalence principle helps explain the appearance of phenocopies. It also points to a general pathway favorable to the occurrence, during evolution, of frequent episodes corresponding to Waddington's genetic assimilation and is likely to represent one component of the system responsible for the high frequency of recurrence of parallel evolution.

Biological Evolution↗
PubMed1988

Down-regulation of an abundant cellular protein associated with tumor progression.

Alteration of gene expression in neoplastic cells can be detected by two-dimensional gel electrophoresis. This study reports the altered synthesis of an abundant cellular protein, p29, accompanying tumorigenic transformation of immortalized fibroblasts induced by transfection with oncogenic DNA. Cell lines derived from morphologically transformed foci synthesized p29 at 60-75% reduced levels compared with untransformed parental cells. Upon inoculation into syngeneic immunocompetent animals, transformed cells gave rise to tumors which were excised and established in culture. The amount of p29 in both focal and tumor-derived lines was inversely correlated with the latent period for tumor formation. In cell lines with a tumor latency of 12-20 days, the level of p29 was decreased by 90-99%. In rapidly tumorigenic cells with a short latency (3-6 days), p29 synthesis was not detectable. These data demonstrate that p29 may be a sensitive and reliable marker for tumor progression of fibroblasts.

Animals↗
PubMed1987

On the molecular evolutionary clock.

The conceptual framework surrounding the origin of the molecular evolutionary clock and circumstances of this origin are described. In regard to the quest for the best available molecular clocks, a return to protein clocks is conditionally recommended. On the basis of recent data and certain considerations, it is pointed out that the realm of neutrality in evolution is probably less extensive than is now commonly thought, in the three distinct senses of the term neutrality--neutrality as nonfunctionality of mutations, neutrality as equifunctionality of mutations, and neutrality as a mode of fixation of mutations. The possibility is raised that complex sets of interacting components forming a system that is bounded with respect to its environment may quite generally display an intrinsic trend to a quasi-clockwise evolutionary behavior.

Biological Evolution↗
PubMed1986

Quantitative protein profiling: determining lexotypes.

The lexotype of a cell is defined as a set of quantitative characters of its informational macromolecular gene products, notably proteins, as observed under specified environmental conditions. This definition can be applied to cells in several ways that need to be distinguished. It can refer to the protein lexotype, to RNA lexotypes; to the steady-state lexotype, synthesis lexotype, functional protein lexotype; to the in situ lexotype and standard-environment lexotype. When used without qualification, the term lexotype may be applied to the standard-environment, steady-state protein lexotype. Some difficulties that currently limit our ability to determine lexotypes are assessed. Reasons are given why abnormal cellular states, such as states of disease, should often be characterizable by means of protein markers not themselves involved in the disease process and why one expects to find markers in tissues other than the one in which a certain pathological process may be anticipated to occur. There are three routes through which biological systems can produce secondary protein markers, namely through gene regulatory chains, through chromosomal gene linkage, and through "physiological linkage" of genes. The partly stable, partly shifting, yet defined relations between tissue lexotypes are considered. A number of potentially important fields of application of rigorous quantitative analyses of protein profiles are listed. One particular use of the technology is to investigate a hypothesis linking aging to degenerative diseases with late onset. According to this hypothesis, such diseases appear in later life as the cellular concentration of the active form of a protein passes a certain threshold in the course of the aging process.

Aging↗
PubMed1986

Age-dependent changes in proteins of Drosophila melanogaster.

Several molecular theories of aging postulate that there are age-dependent changes in gene expression and that these changes contribute to the reduction in the viability of senescent cells. High-resolution, semiautomated, quantitative two-dimensional gel electrophoresis of many soluble proteins was used to test this hypothesis in Drosophila. Two-dimensional protein gel patterns were analyzed for each of three age groups of [(35)S]methionine-labeled adult male Drosophila melanogaster, which, except for their spermatocytes, consist entirely of fixed postmitotic cells. Seven relatively abundant polypeptides expressed in middle-aged (28-day-old) flies were absent in both young(10-day-old) and old (44-day-old) flies. Quantitative analyses of an additional 100 polypeptides were carried out by computer-assisted microdensitometry of fluorograms of the gel preparations. These analyses revealed a significant age-related heterogeneity in the quantitative distribution of radiolabel in these proteins. The data indicate that the qualitative pattern of gene expression is identical in young and old flies, but that profound quantitative changes occur in the expression of proteins during the Drosophila life-span.

Aging↗