Mutat Res. 2017 Jan;795:27-30.

A novel type of gene interaction in D. melanogaster 

Boris F. Chadov * , Eugenija V. Chadova, Nina B. Fedorova

From the Institute of Cytology and Genetics, Siberian Department of Russian Academy of Sciences, Novosibirsk 630090, Russian Federation.

*Correspondence should be addressed to Boris F. Chadov. Institute of Cytology and Genetics, Siberian Department of Russian Academy of Sciences, Novosibirsk 630090, Russian Federation. E.mail: boris_chadov@mail.ru 

 

Abstract

The genes interact according to classical mechanisms, namely, complementation, modification, polymery, and epistasis, in the cells and organisms carrying these genes. Here we describe a novel type of gene interaction when the interacting genes reside in parents, whereas the interaction event takes place in their progenies lacking these genes.

The conditional mutations in the D. melanogaster male X chromosome caused the “prohibition on producing daughters” in its offspring. The chromosomal rearrangements in chromosomes 2 and 3 of its female partner removed the prohibition. The phenomena of “prohibition” and “removal of prohibition” appeared as a parental effect in both the male and female. Both phenomena ensued from the presence of the studied mutations in parents rather than their unviable or survived progenies. Thus, the gene interaction when the genes themselves are absent at the site of interaction and during the interaction event takes place in drosophila.

PMID: 28103492

 

Supplement:

The conditional mutations in the Drosophila melanogaster, residing in males, do not interfere with their viability; however, the mutations when they are present in the daughters of the males crossed to yellow females act as dominant lethals [1]. The progenies of such crosses comprise only yellow sons (Fig. 1, upper left panel). This phenomenon got the name “prohibition on daughters in the progeny”. A chromosomal rearrangement in chromosome 2, the Curly inversion, introduced into the female yellow genome removes the prohibition on daughters in the progeny (Fig. 1, lower left panel). An interaction of the mutation and the rearrangement is evident. However, the character of this interaction is rather unusual.

First, the daughters Cy+ (females «+» without the rearrangement) for some unknown reason appear along with the Cy daughters (Fig. 1, lower left cell). Second, the Cy inversion when introduced into the mutant male genome for some reason ceases to cause production of daughters. The progeny of yellow females comprises only sons despite the presence of the Curly inversion (Fig. 1, right upper cell). These two additional phenomena make the fact of interaction between mutation and rearrangement look as a kind of genetic logical task. The solution for the task should be a unified interpretation of the overall phenomenology of the interaction between a conditional mutation and a chromosomal rearrangement.

Current genetics explains the mechanism of gene interaction using two tools, RNA and protein. This is insufficient to solve the problem we discuss. The proposed solution (Fig. 2) utilizes additional tool, namely, epigenetic (epinucleotide) modification of the genome caused by the action of genes. It is assumed that modification of the genome is a normal process taking place in both the female and male gametogenesis before meiosis. The modification is performed by ontogenes. The conditional mutations in the X chromosome are mutations in the ontogenes residing in the X chromosome [2]. The chromosome inversion Cy also manifests itself as a mutation of ontogenes [3].

 

 

 

Fig. 1. The phenomenon of “prohibition on daughters in the progeny” in D. melanogaster. In the first cross, yellow females were mated to the males carrying a conditional mutation in the X chromosome. In the second cross, the yellow females carrying additional Curly inversion in chromosome 2 were used. In the third cross, the males carried both the conditional mutation in the X chromosome and Curly inversion. The prohibition on daughters in the progeny appeared in the first and third crosses: the progeny contains exclusively sons. This phenomenon was absent in the second cross: both Cy and Cy+ daughters appeared in the progeny.

 

As is assumed, the Cy inversion interferes with genomic modification in the maternal genome of yellow strain and the presence of conditional mutation in the X chromosome interferes with the modification in the paternal genome. Figure 2 shows that the maternal and paternal genomes contain local defects, namely, conditional mutation of an ontogene in male (red region) and inversion in female (blue region). However, ontogenes are activated during gametogenesis, entailing modifications of the whole maternal and paternal genomes. As a result, the gametes not only carry the corresponding mutations, but are also modified. Modification of the genomes is denoted by painting the chromosome sets with the colors of the corresponding mutations.

Figure 2 in its structure is the Punnett square, well known in genetics. In classical genetics, it is used to display the variants of sets of alleles inherited by the progeny from parents. Figure 2 differs from the classical Punnett square by that it reflects a fundamentally new genetic process. Painting of the chromosome sets with the same color as the parental mutation reflects the process of genome modification by ontogenes taking place in gametogenesis. Gametogenesis in the classical genetics is sorting of an inactive parental genome by gametes. The results of the conducted experiment suggest that this idea is true only for one category of genes, namely, the Mendelian genes. As for the ontogenes, they are active in gametogenesis and implement epigenetic fine-tuning of the genome (in other words, its modification) necessary for the forthcoming individual development of the progeny. Ontogenes convert gametogenesis from mere sorting of inactive genetic material into an active process of genome transformation.

 

 

Fig. 2. Explanation of the interaction between conditional mutations and chromosomal rearrangement by an epigenetic modification of the genomes during gametogenesis. The male carries a conditional mutation in the X chromosome (red-colored region). The mutation during spermatogenesis causes epigenetic modification of the entire diploid genome of spermatocytes. Thus, all male gametes are modified (red). The female carries the Cy inversion in autosome 2 (blue region). The inversion during oogenesis causes epigenetic modification of the entire genome of oogonia. All female gametes are modified (blue). The properties of the progenies now depend not only on the presence of mutations introduced to the genome of the progenies by their parents, but also on the result of interaction between the epigenetically modified chromosome sets in the gametes.

 

The epigenetic modifications of paternal and maternal genomes are compared in the zygote. The result of this comparison either allows the zygote to continue its development or leads to its death. In essence, the phenomenon of interaction between the Cy inversion and a conditional mutation is the aggregate total of interactions between the modifications that have been caused by these mutations. Thus, the mechanism underlying this interaction comprises two stages. The first stage takes place in gametogenesis and the second, in the zygote when two chromosome sets are joined. The effect of Cy in gametogenesis before the reduction division, the first division of meiosis, explains the emergence of Cy+ daughters. Formation of a daughter depends on the genome modification caused by Cy before the first meiotic division rather than the presence or absence of the Cy inversion in a progeny.

The event of comparison of epigenetic modifications takes place when the paternal and maternal chromosome sets meet in the zygote. In particular, a conditional mutation in the X chromosome and Cy inversion interact in the case when they enter the zygote from different parties, paternal and maternal. The absence of the effect of Cy inversion within a male genome is explainable by that the mutation in the X chromosome and inversion enter the zygote from the same party, paternal. The proposed uniform explanation for all three phenomena-(1) interactions between a conditional mutation and Cy inversion; (2) emergence of Cy+ females; and (3) the absence of the effect of Cy inversion in mutant males-allows us to consider that the solution of the problem on the mechanism of interaction is obtained.

In its form, the gene interaction described here differs from all types of gene interactions known in the classical genetics. All classical types of interactions (complementation, modification, polymery, and epistasis) take place in the cell or organism containing the inactive genes together. In this case, the interacting genes (conditional mutation and chromosomal rearrangement) reside in the parents individually, while the very event of interaction takes place in the progeny.

The novel type of interaction both in its form and content differs from the classical interaction. First, the players here are “the other” type of genes (ontogenes) rather than the classical ones. Second, implementation of the ontogene activity includes an epigenetic event, namely, epinucleotide genome modification. The earlier described development of morphoses (developmental abnormalities), which gave their name to ontogenes [4], is also an epigenetic event. The new type of interaction confirms that a special category of genes for which an epigenetic (epinucleotide) implementation is the norm do exist in the genome.

A molecular nature of the ontogenes is yet to be studied; however, general considerations suggest that ontogenes are regions of DNA residing in introns. The rate of mutations in ontogenes is higher as compared with the Mendelian genes; ontogenes act as regulators of gene activity and drastically differ from the Mendelian genes in the pattern of inheritance. The specific features of conditional mutations in drosophila and their manifestation [2, 3] suggest that ontogenes are the particular structure that forms the basis for the traits not subject to Mendelian inheritance. First and foremost, this refers to the human diseases that combine a hereditary component with a completely unclear inheritance pattern.

Indeed, the pattern of formation of morphoses and modifications in the carriers of conditional mutations demonstrates most unpredictable character of this pathology [4]. It rather resembles inheritance of some widespread human diseases. The type of interaction considered in this paper demonstrates how the classical strong connection between a Mendelian gene and a trait is disturbed, while the presence of “a trait without the gene” and “a gene without the trait” becomes a rule. The dependence of ontogene manifestation on the genome of the partner in cross adds peculiarity to the traits formed with the help of ontogenes.

Comparison of epigenetic genome modifications in the zygote is the test for compatibility of genomes. One of the results in this test is the death of zygotes. In this sense, ontogenes are of interest to reveal the causes of variation in human fertility in the norm and pathologies.

The current genetic literature, in particular, on human diseases, is rich with the facts demonstrating an epigenetic control of biological traits. In this paper, epigenetic control is a component of gene performance. We should also keep in mind that this is a special group of genes distinct from the Mendelian genes. They are referred to as ontogenes.

Among the types of gene interaction described by classical genetics (complementation, modification, polymorphism and epistasis), strangely enough, there was not the most important type of interaction. This is a gene interaction for the implementation of the program of individual development. It can be assumed that the presented type of gene interaction serves as a tool for constructing and implementing of  individual developmental program.

 

References

1. B.F. Chadov, E.V. Chadova, S.A. Kopyl, N.B. Fedorova, 2000 A new class of mutations in Drosophila melanogaster, Dokl. Biol. Sci. 373 (2000) 423–426.
2. N.B. Fedorova, E.V. Chadova, B.F. Chadov, Genes and Ontogenes in Drosophila: The Role of RNA Forms // Transcriptomics 4, 2016, pp. 137, http://dx.doi.org/10.4172/2329-8936.1000137.
3. B.F. Chadov, N.B. Fedorova, E.V. Chadova, Conditional mutations in Drosophila melanogaster: On the Occasion of the 150th Anniversary of G. Mendel’s Reportin Brünn, Mutat. Res./Rev. Mutat. Res. 765 (2015) 40–55, http://dx.doi.org/10.1016/j.mrrev.2015.06.001.
4. B.F. Chadov, E.V. Chadova, N.B. Fedorova, Epigenetic phenomenology in conditional mutants of Drosophila melanogaster: morphoses and modifications, In: S.M. Zakijan, S.M. Vlasov, E.V. Dement’eva (Eds.), Epigenetics, SD RAN, Novosibirsk (2012) 499–533 (in Russian).

 

Boris F. Chadov,

Eugenia V. Chadova,

Nina B. Fedorova.