Inbreeding Depression and Heterosis: Explanation by Two-Component Genome Composition
Siberian Department of Russian Academy of Sciences, Institute of Cytology and Genetics, Novosibirsk, Russia
Citation: Chadov BF (2018) Inbreeding Depression and Heterosis: Explanation by Two-Component Genome Composition. SCIOL Genet Sci 2018;1:41-44.
Inbreeding in animals and plants leads to the formation of weak and low-fertile offspring (inbreeding depression). The reverse phenomenon, i.e. the formation of strong and high-fertile offspring, superior to their parents (heterosis), occurs when crossing representatives of a species distant by kinship. Hypotheses about the mechanism of inbreeding depression and heterosis converge in the genetic cause of the phenomena. Everything is decided by the level of genome homozygosity: it is at its maximum in the inbreeding depression, and at its minimum in heterosis 3. However, the mechanism by which the level of homozygosity affects the offspring habitus has not yet been clarified. The new data obtained by the author and their colleagues on the structure of the genome make it possible to explain the phenomena. According to the data, the genome is two-component: in addition to the classic Mendelian genes, it contains ontogenes controlling ontogenesis. Ontogenes in the normal genome are in a homozygous state. If this is the case, the procedure of maximum genome heterozygotization will result in homozygous ontogenes appearing against the background of heterozygous Mendelian genes. The resulting contrast can facilitate the recognition of homozygous ontogenes and their launch into work (the phenomenon of heterosis). The genome homozygotization process should, on the contrary, disguise the location of homozygous ontogenes among the same homozygous genes. Recognition of ontogenes and their launch into work will be complicated (the phenomenon of inbreeding depression). Previous hypotheses attempted to discern the cause of the phenomena in different behaviors of the one-component genome. In the proposed hypothesis, the cause lies in the two-component composition of the genome and the influence of some genes on the work of other genes at the stage of sequence recognition.
The unfavorable consequences of inbreeding and, vice versa, the beneficial effects of distant crossing are phenomena that have been known to man since ancient times. They are taken into account in the structure of human marital relations, as well as in agriculture when breeding animals and plants. In genetics these are inbreeding depression  and heterosis . There are many hypotheses about the nature of these phenomena . The hypotheses emanate from indisputable facts: increasing the genome homozygosity leads to depression and increasing its heterozygosity leads to heterosis. The problem is that the experience of classic genetics shows that hetero- and homozygosity for a single gene does not generally affect the viability of an individual. Therefore, logic suggests that increasing the number of homo- or heterozygous genes does not explain the heterosis and depression. The phenomena cannot be explained by the appearance of homo- or heterozygotization of the epistatic interaction of genes in the process. If not all, then many genes, as Gregor Mendel showed are independent of each other. This means that, as a type of gene interaction, epistasis is not common enough to be drawn on to explain such common phenomena as heterosis and inbreeding depression.
The very fact that the heterozygote (heterosis) has the highest viability is surprising for geneticists. It is generally believed that the factors (alleles) that increase the viability of an organism are brought by selection into a homozygous state. In this case, the highest viability must have homozygotes and not heterozygotes. It is incomprehensible why nature demonstrates the opposite in the case of heterosis. The phenomena of heterosis and inbreeding depression have previously been referred to as "a challenge to genetics" .
Recently, genes have been found that differ from traditional Mendelian genes by a special function-control of ontogeny and a special way of implementing this function [5,6]. The genes are called ontogenes [7,8]. Their remarkable feature is the homozygous presence in the genome. In the heterozygote they are no longer regulators, but initiators of the death of the organism - the dominant lethals [9,10]. In the new situation, taking into account the existence of ontogenes, the active genomic DNA consists of two components: traditional genes for which the hetero- and homozygosity states are equally normal, and ontogenes for which the only working state is homozygosity. If, in this case, the two-component genome faces the task of changing the heterozygosity (or homozygosity) level, the change will only affect the part of the genome consisting of traditional genes. The other part, consisting of ontogenes, will not accept the changes. It remains homozygous since the mutations in the ontogene are in the heterozygote and die [5,7].
An increase in the heterozygosity of the genome occurs as a result of outbreeding (successive crosses of forms, distant by kinship) and an increase in homozygosity occurs as a result of inbreeding (crossing of forms which are close by kinship to the maximum extent). Imagine now (Figure 1) what effect the genome will have on outbreeding and inbreeding in the case of the classic one-component genome (genes only) and in the case of a two-component genome (genes + ontogenes). With maximum heterozygosity (1), the one-component genome A is found to be entirely heterozygous A (1) (all of the genes are dark), and the two-component genome B is only partially heterozygous B (1). The ontogenes (white) cannot become heterozygous. They are homozygous by definition. The pattern of mutual arrangement of genes (a, c, e, g) and ontogenes (b, d, f) in the two-component model is marked (alternation of dark and light areas).
Figure 1: States of maximum hetero- and homozygosity in one - and two-component genomes. View Figure 1
The diploid genome is depicted as a pair of chromosomes with centromeres (white circles). A genome has seven discrete hereditary units: a b c d e f g. In a one-component genome (A), all seven are genes (grey). In a two-component genome (B), there are four genes: a, c, e, g (grey) and three ontogenes: b, d, f (white). The grey colour shows the heterozygous state and the white colour shows the homozygous state of the hereditary unit. The upper line (1) Is the maximum genome heterozygosity achieved by outbreeding, and the lower line (2) Is the maximum genome homozygosity achieved by inbreeding. In the one-component genome (A), the change from maximum heterozygosity (A1) to maximum homozygosity (A2) does not change the genome differentiation ("grey" homogeneity is replaced by "white" homogeneity). In the two-component genome (B), the differentiation changes: "the presence of pattern" (B1) changes to its absence (B2).
With maximum homozygosity (2), the one-component (A2) and two-component (B2) genomes become completely homozygous. Both are entirely light. The result of homozygotization of a one-component genome is not significant: the homogeneity of the genome is preserved, only its form changes (grey A (1) changes to white A (2)). The result of homozygotization of the two-component genome (B2) is very noteworthy: The genes and ontogenes arrangement pattern disappears. All seven sections of the genome are light; the genes are now not distinguishable from the ontogenes. In the one-component genome, a change in function is not expected when maximum heterozygosity changes to maximum homozygosity, since for a single gene there is no systematic difference in function between the heterozygote and homozygote. In other words, the one-component model of the genome has no prerequisites for the onset of heterosis and inbreeding depression.
In the two-component model, complete heterozygosity of the genome leads to maximum exposure of the pattern of the ontogene arrangement among the genes (B1), and complete homozygosity leads to the masking of this pattern (B2). It can be assumed that these two genome states are the cause of heterosis and inbreeding depression. Heterozygosity in Mendelian genes should favour the work of ontogenes because it will stand out due to their homozygosity and it will be easier for their products to find their targets (also ontogenes). Homozygosity in Mendelian genes will interfere with the work of ontogenes; the ontogenes will be "lost" among them since both categories of the genes will be represented by the pairs of homozygous alleles. The hypothesis about the causes of heterosis and inbreeding depression, as shown is based on the previously discovered property of ontogenes to work normally only in the homozygote. In addition to its direct purpose, the hypothesis explains so-called "monogenic heterosis" [11,12] rare cases of increasing viability of a heterozygote over homozygote in individual genes. In accordance with the hypothesis, the state of the gene adjacent to the ontogene is more important than the state of the genes remote from it. After all, it is the genes adjacent to ontogenes that take part in the formation of the dividing line and "signal" the presence of the ontogene in this area. It can be expected that the genes immediately adjacent to the ontogene will have the distinct effect of "monogenic heterosis". This assumption indicates the approach to experimental verification of the proposed hypothesis. It will be confirmed if it is proven to be the genes directly bordering the ontogenes that affect the viability of an individual when transferring from a homo- to heterozygous state (and vice versa).
The proposed hypothesis opens up approaches to explaining other phenomena in the field of heterosis. These include the varying strength of heterosis in various combinations of inbreeding lines of common origin, the phenomenon of absence of depression in self-pollinators, the possibility of changing the system of reproduction in plants, etc. It is logical to assume that in the process of realizing the genetic information, the genome periodically faces the problem of recognizing genes and ontogenes. We can specify at least two genetic situations in which discrimination of the location of genes and ontogenes will be highly desirable. The first refers to the genomes' encounter during zygote formation. It is shown that some of the zygotes die due to mismatch of the functional state of the set of ontogenes on the mother's side with the functional state of the ontogenes on the father's side . In this case, it seems optimal that only the parts composed of ontogenes, rather than the genomes of the parents as a whole, are subjected to mutual verification. It is desirable that the former would somehow stand out in the total mass of genes. The second situation concerns the pairing of homologous chromosomes. The pairing occurs both in meiosis and in mitosis. The homologs unite in pairs, despite heterozygosity, in small (alleles of point genes) and large chromosome regions (chromosomal rearrangements). It is logical to assume that the decisive factor for the pairing is the presence of obligate homozygous regions. They are represented by ontogenes. In this situation, as per the previous, the process can be facilitated if the obligate homozygous areas in each parent set are clearly distinguished among the others. Both examples show that heterosis and inbreeding depression, by the mechanism underlying them can be related to a number of genetic events.
The two-component model of the genome assumes the presence of both homo-and heterozygous regions in the genome as standard. To preserve both, the selection of genomes should be two-vector. One vector is the increase (preservation) of the genome homozygosity. Homozygosity is achieved by eliminating mutations in ontogenes. The other vector is the increase (preservation) of the genome heterozygosity. Heterozygosity is achieved by mutagenesis. It helps to optimise the work of ontogenes. The existence of heterosis and inbreeding depression phenomena confirm the actual existence of two-vector selection and cases of the predominance of one state of the genome over another. Since the two selection vectors are oppositely directed, the genetic system is forced to adhere to the strategy of compromise solutions. In biology, this is called "self-organisation". It can be seen that the issues of heterosis and inbreeding depression have a common biological aspect. The explanation of heterosis and inbreeding depression is the third case where the idea of ontogenes is used in order to resolve genetic problems. The idea of ontogenes has already been used to resolve some of the problems of ontogenesis  and phylogenesis . The statement about the existence of ontogenes replaces the classic notion of the one-component genome composition with the concept of its two-component structure.
The authors thank the Federal Research Center «Institution of Cytology and Genetics of Russian Academy of Sciences» for providing financial support for this work (budget project no. 0324-2018-0019) and A.A. Fedorov for his assistance with the artwork.
- Mather K. Variation and selection of polygenetic characters. Journal of Genetics 1941;41:159-93.
- Shull GH. Experiments with maize. Botanical Gazette 1911;52:480-5.
- Strunnikov VA. The Nature and problems of heterosis. Priroda, Moscow, Russian. 1987;5:64-76.
- Strunnikov VA, Strunnikova LV. Heterosis Can Be Fixed in the Progeny. Priroda, Moscow, Russia 2003;1:3-7.
- Chadov BF, Chadova EV, Kopyl SA, Fedorova NB. A new class of mutations in Drosophila melanogaster. Dokl Biol Sci 2000;373:423-6.
- Chadov BF, Fedorova NB, Chadova EV, EA Khotskina. Conditional mutations in Drosophila. J Life Sci 2011;5:224-40.
- Chadov BF, Fedorova NB, Chadova EV. Conditional mutations in Drosophila melanogaster: On the occasion of the 150th anniversary of G. Mendel's report in Brünn. Mutat Res Rev Mutat Res 2015;765:40-55.
- Chadov BF. Ontogenes in Drosophila melanogaster: genetic features and role in onto - and phylogeny. In: VL Korogodina, A Chini, M Durante, Modern Problems of genetics, radiobiology, radioecology and evolution. JINR, Dubna, Russia 2007;80-91.
- Chadov BF. The "image" of the regulatory gene in experiments with Drosophila. Russian Journal of Genetics 2002;38:725-34.
- Fedorova NB, Chadova EV, Chadov BF. Genes and Ontogenes in Drosophila: The Role of RNA Forms. Transcriptomics 2016;4:137.
- Rieger R, Michaelis A. Genetisches und Cytogenetisches WÖrterbuch. Springer Verlag 1958;99.
- Khotyleva LV, Kilchevsky AV, Shapturenko MN. Theoretical aspects of heterosis. Vavilov Journal 2016;20:482-92.
- Chadov BF, Chadova EV, Fedorova NB. A Novel Type of Gene Interaction in D. melanogaster. Mutation Research/ Fundamental and Molecular Mechanisms of Mutagenesis 2017;795:27-30.
- Chadov BF, Chadova EV, Fedorova NB. The Genetics of Conditional Mutations and Individual Developmental Programs in D. melanogaster. SCIOL Genet Sci 2017;1:3-21.
- Chadov BF, Chadova EV, Fedorova NB. Orthogenesis and Darwinism: Perspective of their synthesis in light of the conditional mutations data. Modern Problems of Evolution and Ecology. Proceedings of the XXX Lubishev's Reading. 2017;133-42.