THE MITOCHONDRIAL GENETIC SYSTEM ....•••••• ••••••••••.• ••••••••••..•......... 291 Organization and Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . 291 Genetic Content 296 Regulation of Mitochondrial Gene Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300

Biogenesis of Mitochondria

A mechanism for gene conversion is proposed which overcomes many of the difficulties that any copy choice model encounters. It is suggested that along with general genetic pairing of homologous genomes at meiosis, effective pairing over short regions of the genetic material occurs at the molecular level by the separation of the strands of the DNA double helices, followed by the annealing of strands from two homologous chromatids. If the annealed region happens to span a heterozygous site, mispairing of bases will occur. Such a situation may be analogous to that in DNA which is damaged by mutagens; the same or similar repair mechanisms may operate, and these, by adjusting the base sequences in order to restore normal base pairing, would bring about gene conversion in the absence of any genetic replication. The model indicates how precise breakage and rejoining of chromatids could occur in the vicinity of the conversion, so that conversion would frequently be accompanied by the recombination of outside markers. The model also proposes that the distance between two mutant sites on a fine structure map depends not so much on the frequency of a recombinational event occurring between them, but rather on the degree of inhibition of the processes of genetic pairing by the mutants themselves. The model will explain almost all the data in a formal way, and it has the advantage over copy choice mechanisms for gene conversion in (1) being compatible with semi-conservative replication of DNA, (2) not invoking DNA synthesis during or after genetic pairing, (3) providing a molecular mechanism for close specific pairing, (4) making it unnecessary to postulate sister strand exchange or a process akin to this, (5) suggesting why rates of gene conversion in opposite directions are sometimes unequal and (6) providing an explanation of the clustering of mutant sites, a basis for map expansion and for the apparently capricious departure of fine structure maps from additivity. Although the model proposed is a general rather than a specific one, it suggests that the process of conversion and intragenic recombination is more complex than is usually believed, since it depends on several interacting factors. Nevertheless, it is hoped that the introduction of a model with this complexity will help to stimulate specific experiments, and that these will provide definitive information which would never be obtained if simpler models of conversion and intragenic recombination were believed to explain the genetic data sufficiently well.

/pdf/a-mechanism-for-gene-conversion-in-fungi-1tp9iv58rz.pdf

A mechanism for gene conversion in fungi.

We have identified recessive overproliferation mutations by screening and examining clones of mutant cells in genetic mosaics of the fruitfly Drosophila melanogaster. This type of screen provides a powerful approach for identifying and studying potential tumor suppressors. One of the identified genes, lats, has been cloned and encodes a putative protein kinase that shares high levels of sequence similarity with three proteins in budding yeast and Neurospora that are involved in regulation of the cell cycle and growth. Mutations in lats cause dramatic overproliferation phenotypes and various developmental defects in both mosaic animals and homozygous mutants.

Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase

A model is presented whereby the formation of gene clusters in bacteria is mediated by transfer of DNA within and among taxa. Bacterial operons are typically composed of genes whose products contribute to a single function. If this function is subject to weak selection or to long periods with no selection, the contributing genes may accumulate mutations and be lost by genetic drift. From a cell's perspective, once several genes are lost, the function can be restored only if all missing genes were acquired simultaneously by lateral transfer. The probability of transfer of multiple genes increases when genes are physically proximate. From a gene's perspective, horizontal transfer provides a way to escape evolutionary loss by allowing colonization of organisms lacking the encoded functions. Since organisms bearing clustered genes are more likely to act as successful donors, clustered genes would spread among bacterial genomes. The physical proximity of genes may be considered a selfish property of the operon since it affects the probability of successful horizontal transfer but may provide no physiological benefit to the host. This process predicts a mosaic structure of modern genomes in which ancestral chromosomal material is interspersed with novel, horizontally transferred operons providing peripheral metabolic functions.

https://www.genetics.org/content/genetics/143/4/1843.full.pdf

Selfish Operons: Horizontal Transfer May Drive the Evolution of Gene Clusters

The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans.

/pdf/meiotic-recombination-the-essence-of-heredity-4r9furtxsj.pdf

Meiotic Recombination: The Essence of Heredity

Giles [1] has reported that crosses between certain inositol mutants of Neurospora give infrequent wild recombinants, and from the segregation of linked markers it appeared that multiple crossovers might sometimes be involved. The present author subsequently observed that crosses between two closely linked or allelic pyrimidine mutants, one of which carried a "colonial" marker, gave occasional genetically wild offspring, but roughly half of these carried the "colonial" marker and half did not. This was surprising, since the marker appeared to be located only two or three units from the pyrimidine locus or loci, and, if the wild recombinants arose from crossovers between the two pyrimidine mutants, all would be expected to be alike with respect to the marker unless, in half the cases, a second crossover occurred between the pyrimidine locus and the locus of "colonial." These observations will be described in detail elsewhere. Unfortunately, a closely linked marker on the other side of pyrimidine is not known, and, moreover, crosses between these mutants are regularly semisterile, so that it is not possible to observe complete asci. However, another pair of mutants, requiring pyridoxine, also closely linked to "colonial" was found by Dr. T. H. Pittenger (personal communication) to exhibit the same behavior, and these mutants give fertile crosses. When a suitable marker was located [2] on the other side of pyridoxine, a study of recombinants among random spores and in complete asci was undertaken.

https://www.pnas.org/content/pnas/41/4/215.full.pdf

ABERRANT RECOMBINATION OF PYRIDOXINE MUTANTS OF Neurospora.

The inheritance of mutant characters of Neurospora has not previously been found to be influenced by the way in which crosses were made. Whether protoperithecia were furnished by one parent or the other, the result, in so far as the types of progeny recovered were concerned, was the same. In the case to be considered here, however, the inheritance of a slow-growth character, which has been designated as poky, appears to be dependent upon its being carried by the protoperithecial parent. If the strain which furnishes the protoperithecia is considered to correspond to the maternal parent on the basis that it also furnishes the greater part of the cytoplasm from which the ascospores are derived, then this case appears analogous to those which have been described in other organisms (reviewed by Sonneborn [1]). In its failure to be transmitted (when it is carried by the fertilizing parent and not by the protoperithecial parent) the poky character resembles in behavior the petite character in yeast, described by Ephrussi [2] and his collaborators. A simple comparison of the two cases probably cannot be made, however, since the yeast ascospores arise from a mixture of the cytoplasms of the two parents, whereas, in obligate heterothallic strains of Neurospora, it appears probable that such mixing does not occur. [3-5]

https://www.pnas.org/content/pnas/38/5/442.full.pdf

A Case of “Maternal” Inheritance in Neurospora Crassa

It was reported recently that the characteristics of a slow-growing strain, called poky, are inherited maternally.(1) This observation has focused attention on strains which grow slowly on complete medium and which have long been known to appear very frequently in material examined in order to detect nutritional mutants of Neurospora. An indication of the frequency of their appearance can be obtained from some figures taken from the data of Beadle and Tatum.(2) Among 8795 ascospores isolated from irradiated material during their study by one of the present authors (M.B.M.), 7049 germinated. Of these, 54 gave rise to strains having easily diagnosed requirements for components present in the complete medium used and, therefore, represented the class of nutritional mutants sought. A much greater number, 489, were distinguishable from wild type because of their slower growth on complete medium. Of these 159 did not grow sufficiently to allow their being tested. The remaining 330 were discarded, either because they grew too rapidly on minimal medium, or because they did not give a well-defined response to the growth-factor mixtures present in the complete medium. Similar figures have been reported by Lein, Mitchell, and Houlahan(3) in a description of a variation in the method of
Beadle and Tatum.(2)

http://www.pnas.org/content/39/7/606.full.pdf

Mendelian and Non-Mendelian Factors Affecting the Cytochrome System in Neurospora Crassa.

https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1155&context=agronomyfacpub

Cytochromes and the succinic acid oxidase system of poky strains of Neurospora.

https://www.genetics.org/content/genetics/37/3/217.full.pdf

Mary B. Mitchell

Papers

ABERRANT RECOMBINATION OF PYRIDOXINE MUTANTS OF Neurospora.

A Case of “Maternal” Inheritance in Neurospora Crassa

Mendelian and Non-Mendelian Factors Affecting the Cytochrome System in Neurospora Crassa.

Cytochromes and the succinic acid oxidase system of poky strains of Neurospora.

A Series of Histidineless Mutants of Neurospora Crassa.