Delete and survive: strategies of programmed genetic material elimination in eukaryotes.

Genome stability is a crucial feature of eukaryotic organisms because its alteration drastically affects the normal development and survival of cells and the organism as a whole. Nevertheless, some organisms can selectively eliminate part of their genomes from certain cell types during specific stages of ontogenesis. This review aims to describe the phenomenon of programmed DNA elimination, which includes chromatin diminution (together with programmed genome rearrangement or DNA rearrangements), B and sex chromosome elimination, paternal genome elimination, parasitically induced genome elimination, and genome elimination in animal and plant hybrids. During programmed DNA elimination, individual chromosomal fragments, whole chromosomes, and even entire parental genomes can be selectively removed. Programmed DNA elimination occurs independently in different organisms, ranging from ciliate protozoa to mammals. Depending on the sequences destined for exclusion, programmed DNA elimination may serve as a radical mechanism of dosage compensation and inactivation of unnecessary or dangerous genetic entities. In hybrids, genome elimination results from competition between parental genomes. Despite the different consequences of DNA elimination, all genetic material destined for elimination must be first recognised, epigenetically marked, separated, and then removed and degraded.

INTRODUCTION

Eukaryotic cells maintain and ensure their genome's stability, thereby allowing development of the organism and assuring the transmission of genetic material to offspring. Further, the genetic material of an individual needs to be stable during its transmission to the progeny. Some organisms, ranging from ciliate protozoa to mammals, nevertheless possess complex mechanisms to eliminate selectively some of their genetic material during specific stages of ontogenesis (Tobler, 1986; Dawley & Bogart, 1989; Kloc & Zagrodzinska, 2001; Burt & Trivers, 2009; Schön, Martens & van Dijk, 2009; Wang & Davis, 2014; Smith, Timoshevskiy & Saraceno, 2020). This phenomenon of genetic material elimination was first discovered at the end of the 19th century by T. Boveri in parasitic nematodes, namely Parascaris univalens (reviewed in: Tobler, 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Wang et al., 2017). Using descriptive figures, Boveri depicted the process of genetic material removal in detail, showing that during the development of somatic cells, chromosomes become fragmented and that some regions are lost after the chromatids separate (reviewed in: Tobler, 1986; Müller & Tobler, 2000; Grishanin et al., 2006; Wang & Davis, 2014). This process was named ‘chromatin diminution’ by Herla (1893; cited in Tobler, 1986). Initially, Bovery considered such elimination to occur in all organisms and to be responsible for tissue differentiation (reviewed in: Tobler, 1986; Müller & Tobler, 2000; Grishanin et al., 2006). When this hypothesis was not confirmed in other animals, chromatin diminution was not subsequently investigated in detail. Nevertheless, DNA elimination and other processes in which genetic material is specifically removed have been found in various unrelated groups (Tobler, 1986; Dawley & Bogart, 1989; Kloc & Zagrodzinska, 2001; Burt & Trivers, 2009; Schön et al., 2009; Wang & Davis, 2014; Smith et al., 2020). Chromatin diminution and chromosome elimination were collectively named as ‘programmed DNA elimination’ (Wang & Davis, 2014). Herein, we use ‘programmed DNA elimination’ to refer to processes which were previously known as ‘chromatin diminution’.

Elimination of genetic material is involved in a number of processes across plants and animals, including elimination of B chromosomes, whole parental genome elimination, paternal genome elimination induced by parasitic elements, and selective genome elimination in plant and animal hybrids. Programmed elimination of genetic material may serve as a radical and irreversible form of genome competition, dosage compensation, epigenetic regulation, and inactivation of unnecessary or dangerous genetic elements.

Despite years of research into genetic material elimination, some major questions still remain unresolved: (i) the mechanisms of recognition of the sequences destined for elimination in different animals; (ii) whether these mechanisms are similar among organisms or are unique to each species; (iii) why elimination occurs only in some organisms while the vast majority are not able to eliminate DNA; (iv) whether there are predisposing factors for DNA elimination; and (v) whether it might be possible to use these mechanisms for the manipulation of the genome in research on selection, medicine, and agriculture.

In this review, we discuss the elimination of genetic material in different plants and animals, mechanisms of genetic material elimination, and possible functions of the elimination of DNA sequences. Although brief descriptions of different cases of programmed DNA elimination are available, with a specific focus on the known mechanisms, these mechanisms vary significantly and, thus, each case deserves detailed attention.

UNSELECTIVE ELIMINATION OF GENETIC MATERIAL

Ionising radiation, cytotoxic agents, or deficiencies of some substances can lead to the spontaneous elimination of genetic material from the cell nucleus (Fenech & Crott, 2002; Lindberg et al., 2007; Fenech, 2010; Luzhna, Kathiria & Kovalchuk, 2013). Such stress factors can initiate double‐strand breaks, leading to the formation of acentric chromosome fragments that are unable to attach to the spindle during mitosis and remain in the cytoplasm (Fenech & Crott, 2002; Lindberg et al., 2007; Fenech, 2010; Luzhna et al., 2013). Moreover, merotelic kinetochore orientation, aberrations in chromosome condensation, cohesion, disjunction defects, and telomere–telomere fusion all can cause chromosomal loss even during normal cell division (Fenech et al., 2011; Gregan et al., 2011; Ganem & Pellman, 2012). After cell division, unselectively eliminated whole chromosomes or their fragments are usually enclosed in micronuclei and subsequently degraded (Crasta et al., 2012). Inactive X and Y chromosomes are frequently lost in ageing cells (Stone & Sandberg, 1995; Jones, York & Jackson‐Cook, 2012). Massive chromosomal loss has also been reported in cells undergoing oncological transformation (Gisselsson, 2008; Negrini, Gorgoulis & Halazonetis, 2010; Fenech et al., 2011). In addition to chromosomal lagging and the formation of chromosomal bridges, cancer cells are also characterised by the extrusion of genetic material or even whole chromosomes in micronuclei (Shimizu, Shimura & Tanaka, 2000; Utani, Okamoto & Shimizu, 2011; Kwon, Leibowitz & Lee, 2020). In cancer cells, micronuclei can persist even after several rounds of mitotic divisions and can even return to the main nucleus (Crasta et al., 2012; Zhang, Leibowitz & Pellman, 2013). Moreover, micronuclei can be a source of rearranged chromosomes during chromothripsis (Stephens et al., 2011; Crasta et al., 2012). Chromosomes enclosed in micronuclei undergo intensive fragmentation but segregate again with the rest of chromosomes during the next round of division (Crasta et al., 2012). In the nucleus, the damaged chromosome then undergoes non‐homologous end joining, resulting in highly rearranged chromosomal structures (Crasta et al., 2012; Zhang et al., 2013). Stress‐induced elimination of genetic material is non‐selective and does not occur at specific stage of ontogenesis.

PROGRAMMED ELIMINATION OF GENETIC MATERIAL IN DIFFERENT ORGANISMS

Programmed elimination of genetic material has been found to be mediated by a variety of unrelated processes that appear independently across different taxa. In contrast to the unselective elimination of genetic material, programmed elimination of genetic material is highly specific for eliminating DNA sequences and usually occurs during specific stages of ontogenesis (see Fig. 1 for an overview).

Fig 1

Overview of programmed DNA elimination during ontogenesis in multicellular model organisms. Normal ontogenesis without programmed DNA elimination is represented in the centre. Chromatin diminution, elimination of supernumerary and sex chromosomes, paternal genome elimination, parasitically induced genome elimination, and elimination of one parental genome in hybrids are shown according to the timing of elimination during ontogenesis. For specific details of each of the cases of programmed DNA elimination see Figs 2, 3, 4, 5, 6, 7, 8. GRC, germline‐restricted chromosome; PSR, paternal sex ratio.

Fig 2

Chromatin diminution in sea lamprey (A) and parasitic nematode (B). See Fig. 1 for key. The image of the four‐cell embryo indicates that elimination takes place during early developmental stages. Eliminated (red) and retained (violet) chromosomes and their fragments are shown in the karyotype and during mitosis in the boxed images on the right. (A) In sea lamprey, the eliminated fragments or whole chromosomes do not attach to the spindle and lag during anaphase. Progenitors of germ cells keep their genome intact. (B) During chromatin diminution in progenitors of somatic cells in nematodes, the eliminated fragments of holocentric chromosomes do not attach to the spindle and are eliminated during anaphase. Progenitors of germ cells keep their genome intact. See text for further details.

Fig 3

Supernumerary chromosome elimination in goatgrass (A), sciarid flies (B, C) and the zebra finch (D, E). Eliminated (red) and retained (violet) chromosomes are indicated in karyotypes in cells during interphase, in mitosis, and in meiosis in the boxed images on the right. The images of the four‐cell embryo or gonad indicate that elimination takes place during early developmental stages or during gametogenesis, respectively. (A) Elimination of the B chromosome occurs in proto‐root cells of the plant embryo but not in cells from the upper part of the plant. (B, D) Elimination of the B chromosome occurs only in progenitors of somatic cells of the embryo in sciarid flies and the zebra finch. (C) Elimination of the B chromosome via budding from the interphase nucleus occurs in germ cells of sciarid flies. (E) Elimination of the B chromosome during meiosis in zebra finch males. See text for further details.

Fig 4

Sex chromosome elimination in bandicoots (A) and sciarid flies (A, B). Eliminated (red) and retained (violet) chromosomes are indicated in karyotypes in cells during interphase and in mitosis in the boxed images on the right. The images of the four‐cell embryo or gonad indicate that elimination takes place during early developmental stages or during gametogenesis, respectively. (A) Elimination of sex chromosomes only from progenitors of somatic cells occurs in the embryo in bandicoots and sciarid flies. (B) Elimination of sex chromosome via budding from the interphase nucleus in germ cells of sciarid flies. See text for further details.

Fig 5

Paternal genome elimination in mealybugs (A, B) and sciarid flies (C). Eliminated (red) and retained (violet) chromosomes are indicated in karyotypes in cells during interphase and in mitosis in the boxed images on the right. The images of the four‐cell embryo or gonad indicates that elimination takes place during early developmental stages or during gametogenesis, respectively. (A) Elimination of all chromosomes from the paternal genome in all cells of the embryo during haplodiploid sex differentiation in mealybugs. (B) Elimination of all chromosomes from the paternal genome during germ cell development in mealybugs. (C) Elimination of all chromosomes from the paternal genome during monopolar spindle formation during meiosis in sciarid flies. See text for further details.

Fig 6

Paternal genome elimination caused by the paternal sex ratio (PSR) chromosome (A) and Wolbachia infection (B). Eliminated (red) and retained (violet) chromosomes are indicated in karyotypes in mitosis in boxed images on the right. The egg and sperm images indicate that elimination takes place after fertilisation. (A) Elimination of whole paternal genome after fertilisation during PSR chromosome infection in parasitoid wasp. The PSR chromosome is indicated in blue in the sperm chromatin and in the karyotypes. The PSR chromosome escapes the elimination of all other paternal chromosomes and segregates with the maternal chromosomes. (B) Elimination of whole paternal genome after fertilisation during Wolbachia infection (blue) in a fruit fly and a parasitoid wasp. The paternal pronucleus is unable to fuse with the maternal pronucleus; paternal chromatin remains condensed during the first zygotic division. See text for further details.

Fig 7

Elimination of one of the parental genomes in interspecific plant hybrids. Eliminated (red) and retained (violet) chromosomes are indicated in the karyotype in cells during interphase and mitosis in the boxed images on the right. Elimination of whole chromosomes from the genome of one parental species during early embryonic development in plant hybrids. Chromosomal elimination due to lagging during mitosis (upper row) and budding from the interphase nucleus (lower row). See text for further details.

Fig 8

Elimination of one of the parental genomes in animal hybrids reproducing clonally via kleptogenesis (A), gynogenesis (B), androgenesis (C), hybridogenesis (D, E), and meiotic (triploid) hybridogenesis (F). Eliminated (red) and retained (violet) chromosomes are indicated in karyotypes and meiosis. The egg and sperm images indicate that elimination takes place after fertilisation; the gonad image indicates that elimination takes place during gametogenesis. (A) Elimination of the paternal (upper panel) or maternal (middle panel) genomes, or partial replacement of maternal chromosomes (lower panel) during kleptogenetic reproduction in hybrid salamanders from the genus Ambystoma. (B) Elimination of the paternal pronucleus after fusion with the maternal pronucleus (upper panel) and without fusion (lower panel) during gynogenetic reproduction in hybrid fishes from the genus Carassius. (C) Elimination of the maternal genome after fertilisation via the formation of two secondary polar bodies during androgenetic reproduction in hybrid molluscs from the genus Corbicula. (D, E) Mechanisms of parental genome elimination in hybrid water frogs from the genus Pelophylax (D) and poecilid fishes (E). (D) Chromosomes of one of the parental genomes are gradually lost via lagging during mitosis (upper row) or budding from the interphase nucleus (lower row). (E) Chromosomes of one of the parental species attach to the spindle while those of the other parental species are not capable of doing so. (F) Genome elimination during meiosis in triploid hybrid loach from the genus Misgurnus. Chromosomes from the double‐copy genome form bivalents that are able to attach to the spindle while those from the single‐copy genome form univalents that are unable to attach to the spindle, and hence are eliminated during anaphase. See text for further details.

Programmed DNA elimination

Programmed DNA elimination collectively refers to elimination of chromosomal fragments from progenitors of somatic cells in different multicellular organisms and ciliate protozoa (Tobler, 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Wang & Davis, 2014; Smith et al., 2020) (Fig. 2; see online Supporting Information, Table S1). Programmed DNA elimination has been found in species from different classes of ciliates [Oligohymenophorea (Paramecium and Tetrahymena), Spirotrichea (Euplotes, Oxytricha, and Stylonychia)], and in at least 11 species of parasitic nematodes, 8 copepods, and in lampreys, and hagfish (Tobler, 1986; Nakai, Kubota & Kohno, 1991; Prescott, 1994; Grishanin et al., 2006; Smith et al., 2009; Wang & Davis, 2014). In multicellular organisms, programmed DNA elimination occurs in the progenitors of somatic cells during early developmental stages (usually at the 2–6 cleavage divisions stage, but in lampreys between the gastrula and blastula stages) (Fig. 2) (Tobler, 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Smith et al., 2020). In ciliates, programmed DNA elimination occurs during macronucleus formation and is accompanied by genome rearrangements (Tobler, 1986; Prescott, 1994; Mochizuki et al., 2002; Fang et al., 2012). Note that the macronucleus is functionally similar to the somatic cell nucleus in metazoans (Prescott, 1994). Genomes of germ cell progenitors in multicellular organisms and micronuclei in ciliates remain intact and retain all DNA sequences (Tobler, 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Smith et al., 2020).

During DNA elimination, chromosomes undergo radical and irreversible rearrangements; subtelomeric and/or interstitial DNA sequences are excised and subsequently degraded (Beermann, 1977; Tobler, Etter & Müller, 1992; Goday & Pimpinelli, 1993; Müller & Tobler, 2000; Clower et al., 2016; Grishanin & Zagoskin, 2018) (Fig. 2). In nematodes, following DNA breaks chromosomal fragment ends are healed with de novo telomere addition (Müller & Tobler, 2000; Wang et al., 2020) (Fig. 2B). In other species, chromosomal fragments may fuse to form new retained chromosomes (Beermann, 1977; Kubota et al., 2001; Grishanin & Zagoskin, 2018; Timoshevskiy, Timoshevskaya & Smith, 2019). Not only chromosomal fragments, but whole chromosomes can also be eliminated from progenitors of somatic cells during the early embryonic development of lampreys and hagfish (in lampreys, this process is also known as ‘programmed genome rearrangements’) (Nakai et al., 1991; Smith et al., 2009; Covelo‐Soto et al., 2014; Timoshevskiy et al., 2016, 2019). The proportion of eliminated genomes in different species usually varies from 25 to 90%; however, in some ciliate protozoa or copepod species, it can reach 98% of all genomic DNA (Tobler, 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Smith et al., 2009; Fang et al., 2012; Wang & Davis, 2014; Wang et al., 2017). Eliminated sequences usually include high‐copy tandem repeats, other repetitive sequences including copies of transposons, and unique sequences that are known to participate in gametogenesis but are not essential for somatic cells (Aeby et al., 1986; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Fang et al., 2012; Wang & Davis, 2014; Smith et al., 2020) (Table S1).

Since the discovery of programmed DNA elimination, it has been considered relevant to cell differentiation mechanisms and the segregation of germ and somatic cell lines (Tobler, 1986; Smith et al., 2012; Wang & Davis, 2014; Wang et al., 2017; Timoshevskiy et al., 2019). In addition, programmed DNA elimination may affect gene expression and regulate the amount of heterochromatin in progenitors of somatic cells (Tobler, 1986; Kubota et al., 2001; Grishanin et al., 2006; Smith et al., 2012; Grishanin, 2014; Wang et al., 2017; Timoshevskiy et al., 2019) (Table S1). Moreover, increasing evidence suggests that approximately 5–10% of genes (depending on the species) are eliminated in nematodes (Wang et al., 2017). The majority of these eliminated genes are responsible for spermatogenesis, suggesting a particular role of programmed DNA elimination in regulation of the development and maturation of male germ cells (Wang et al., 2017). However, the most important function of DNA elimination appears to be the regulation of parasitic elements in the genomes of these organisms, since large parts of eliminated sequences are represented by transposons or their fragments (Aeby et al., 1986; Schoeberl & Mochizuki, 2011; Fang et al., 2012; Smith et al., 2012; Grishanin, 2014; Wang et al., 2017) (Table S1). One of the most fascinating examples bridging the emergence of programmed DNA elimination with transposable element control during oogenesis can be found in some copepod species (Sun et al., 2014). In these species, during oogenesis the size of the oocyte genome increases dramatically (in some species up to 100 times) due to uncontrolled activity of mobile elements. After fertilisation, DNA elimination purges these elements, restoring normal genome size.

Elimination of supernumerary chromosomes

Whole chromosomes can be eliminated from somatic cells, although they remain preserved in germ cells of at least one of the sexes (Gerbi, 1986; Hennig, 1986; Herrick & Seger, 1999; Torgasheva et al., 2019; Smith et al., 2020) (Fig. 3; Table S1). Individual chromosome elimination usually occurs during cell division and is not associated with chromosomal rearrangements (Gerbi, 1986; Herrick & Seger, 1999; Kloc & Zagrodzinska, 2001; Grishanin et al., 2006; Torgasheva et al., 2019; Smith et al., 2020) (Fig. 3). Such chromosomes are known as supernumerary or B chromosomes, and are usually not essential for survival (sometimes they are considered harmful) (Burt & Trivers, 2009; Jones, 2012; Houben et al., 2014). Nevertheless, B chromosomes undergo programmed elimination in selected organisms. When supernumerary chromosomes become highly specific to germ cells and are absent in somatic cells, they are frequently known as germline‐restricted or germline‐limited chromosomes (Gerbi, 1986; Nakai et al., 1991; Pigozzi & Solari, 1998; Goday & Esteban, 2001; Staiber, 2006; Smith et al., 2009; Torgasheva et al., 2019).

Germline‐restricted chromosomes (GRCs) have been discovered in insects and in some vertebrates, including songbirds (order Passeriformes) (Gerbi, 1986; Nakai et al., 1991; Pigozzi & Solari, 1998; Goday & Esteban, 2001; Staiber, 2006; Smith et al., 2009; Covelo‐Soto et al., 2014; Torgasheva et al., 2019) (Fig. 3; Table S1). Supernumerary chromosomes, or В chromosomes, found widely in plants and animals, tend to be maintained in germ cells that allows transmission to the next generation (Pigozzi & Solari, 1998; Goday & Esteban, 2001; Camacho, 2005; Burt & Trivers, 2009; Jones, 2012). However, they are frequently removed from somatic cells (Pigozzi & Solari, 1998; Goday & Esteban, 2001; Camacho, 2005; Burt & Trivers, 2009; Jones, 2012). Different individuals, even from the same population, may have different numbers of В chromosomes or lack them completely (Camacho, 2005; Jones, 2012). For example, in some plants (Jones & Rees, 1982), B chromosomes are found only in above‐ground parts whereas they are eliminated in root cells (Ruban et al., 2020) (Fig. 3A). GRCs and other B chromosomes are thought to have originated from autosomes or their fragments (Burt & Trivers, 2009; Jones, 2012; Houben et al., 2014). A recent study showed that GRCs in the fungus gnat Sciara coprophila resulted from an ancient introgression event possibly via interspecific hybridisation (Hodson et al., 2021). Although these chromosomes usually accumulate repetitive DNA organised into large heterochromatic blocks, they can contain protein‐coding or noncoding RNA genes that play key roles in gametogenesis and germ cell development (Tobler, 1986; Herrick & Seger, 1999; Houben et al., 2014; Biederman et al., 2018; Kinsella et al., 2019; Torgasheva et al., 2019; Malinovskaya et al., 2020; Hodson et al., 2021). Sequencing data showed that genes responsible for gametogenesis and embryonic development have been continuously added to GRCs during their evolution (Kinsella et al., 2019). Thus, the elimination of such chromosomes from somatic cells can affect germ cell and somatic cell segregation (Gerbi, 1986; Goday & Esteban, 2001) (Table S1). Despite originating as parasitic elements, these chromosomes possess mechanisms to prevent their elimination from germ cells, ensuring their survival and preferential transmission to the gametes (Gerbi, 1986; Goday & Esteban, 2001; Jones, 2012; Houben et al., 2014; Malinovskaya et al., 2020).

Sex chromosome elimination during dosage compensation and sexual differentiation

Another relevant process is the elimination of whole chromosomes during sex determination and dosage compensation (Herrick & Seger, 1999; Kloc & Zagrodzinska, 2001; Burt & Trivers, 2009; Wang & Davis, 2014; Smith et al., 2020) (Fig. 4; Table S1). Usually, dosage compensation involves the selective inactivation of paternal (or less frequently, maternal) sex chromosomes (Herrick & Seger, 1999; Deakin et al., 2009). The elimination of inactivated sex chromosomes for irreversible and extreme dosage compensation has been reported in some invertebrates and in vertebrates, including marsupials (e.g. bandicoots from the orders Peramelidae and Peroryctidae, and pseudocheirid opossums) and at least two eutherian species, the spiny mouse (Acomys sp. from Tanzania) and Oregon meadow mouse (Microtus oregoni) (Hayman & Martin, 1965; Watson, Margan & Johnston, 1998; Johnston et al., 2002; Castiglia, Makundi & Corti, 2007; Smith et al., 2020) (Table S1). Notably, in marsupials, sex chromosomes can be eliminated only from certain somatic cells (Close, 1984). For example, the Y chromosome can be eliminated in somatic tissues in males and the X chromosome can be eliminated in somatic tissues in females (Watson et al., 1998).

In invertebrates, sex chromosome elimination is extremely variable, ranging from the elimination of one of the X chromosomes from somatic and germ cells in fungus gnats (Sciara spp., Sciaridae, Diptera) to several rounds of elimination of paternal sex chromosomes in the hessian fly Mayetiola destructor (Cecidomyiidae, Diptera) (Stuart & Hatchett, 1991; Sánchez & Perondini, 1999; Goday & Esteban, 2001; Burt & Trivers, 2009; Sánchez, 2014) (Fig. 4B; Table S1). In males, elimination of both X chromosomes may occur during early embryonic division, allowing sexual differentiation [for example, in springtails (Collembola)] (Dallai et al., 2001; Dallai, Fanciulli & Frati, 2004; Burt & Trivers, 2009) (Table S1). In the nematode genus Strongyloides, only certain parts of chromosomes are eliminated in a sex‐dependent manner (Streit et al., 2016).

Paternal genome elimination

In certain invertebrates, not only sex chromosomes but the whole paternal genome can be eliminated during haplodiploid sex determination, characterised by the generation of haploid males and diploid females (Herrick & Seger, 1999; Burt & Trivers, 2009; Gardner & Ross, 2014; Sánchez, 2014; de la Filia, Bain & Ross, 2015) (Fig. 5; Table S1). Paternal genome elimination has been found in five arthropod orders, including mites (Phytoseiidae, Otopheidomenidae, and Ascoidea), flies (Sciaridae and Cecidomyiidae), springtails (Symphypleona), beetles (Cryphalini), and scale insects (Neococcoidea) (Gardner & Ross, 2014; de la Filia et al., 2015) (Table S1). In the haplodiploid sex‐determination system, males can develop from fertilised eggs and be diploid initially. However, during the early developmental stages, all paternal chromosomes are eliminated from somatic and germ cells (Herrick & Seger, 1999; Burt & Trivers, 2009; Gardner & Ross, 2014; Sánchez, 2014; de la Filia et al., 2015) (Fig. 5A; Table S1). In some organisms, paternal genome elimination does not involve somatic cells, but is restricted to gonia or meiotic cells (Herrick & Seger, 1999; Kloc & Zagrodzinska, 2001; Burt & Trivers, 2009; Gardner & Ross, 2014; de la Filia et al., 2015) (Fig. 5B, C). Despite the established role of paternal genome elimination in sex differentiation, researchers have hypothesised competition between the maternal and paternal genomes (Brown, 1965; Herrick & Seger, 1999) (Table S1). This hypothesis assumes the emergence of mutations that cause genome elimination in the maternal genome and protect the paternal genome from elimination (Herrick & Seger, 1999).

Induced genome elimination

Selective elimination of one of the parental genomes has been found in organisms with a В chromosome called paternal sex ratio (PSR) or those infected with bacteria from the genus Wolbachia (Werren & Stouthamer, 2003; Werren, Baldo & Clark, 2008) (Fig. 6; Table S1). The PSR chromosome, found in parasitoid wasps (Nasonia vitripennis, Trichogramma kaykai), affects the sex ratio of the progeny (Nur et al., 1988; Stouthamer et al., 2001) (Fig. 6A; Table S1). Wasps have a haplodiploid sex determination system, in which diploid eggs develop into females and haploid eggs develop into males. Males transmit PSR chromosomes via the sperm (Werren, Nur & Eickbush, 1987; van Vugt et al., 2003). After fertilisation, the paternal genome is eliminated; however, the PSR chromosome avoids elimination and jumps to the female nucleus in the fertilised egg (van Vugt et al., 2003) (Fig. 6A; Table S1). Elimination of the paternal genome leads to the development of haploid embryos bearing the PSR chromosome (Reed & Werren, 1995; van Vugt et al., 2003; Swim, Kaeding & Ferree, 2012).

Other cases of induced genome elimination may occur during infection by the endosymbiotic bacterium Wolbachia (Werren et al., 2008). Although Wolbachia infects both males and females, it has various effects on host species (Herrick & Seger, 1999; Stouthamer et al., 2001; Werren et al., 2008). One of the most widespread effects of Wolbachia infection is cytoplasmic incompatibility, which involves paternal genome elimination (Werren et al., 2008). Cytoplasmic incompatibility occurs when a male infected with one Wolbachia strain is crossed with a female infected with another strain. After fertilisation, the paternal pronucleus is unable to fuse with the maternal pronucleus and is degraded in the cytoplasm, thus giving rise to haploid offspring (Fig. 6B; Table S1). Depending on the species, these offspring either die or develop into uninfected males (Reed & Werren, 1995; Tram, Ferree & Sullivan, 2003; Werren et al., 2008). Crosses between two parents infected with the same strain and between an infected female and an uninfected male do not lead to paternal pronucleus elimination via cytoplasmic incompatibility, allowing the normal development of infected diploid females (Reed & Werren, 1995; Herrick & Seger, 1999; Tram et al., 2003; Werren et al., 2008).

These cases of paternal genome elimination demonstrate how parasitic elements can effectively exploit the sex‐determination system of some insects to propagate to the progeny or decrease the number of uninfected individuals (Werren & Stouthamer, 2003; Werren et al., 2008; Burt & Trivers, 2009).

Chromosome elimination in interspecific plant hybrids

Since early experiments involving artificial fusion of cells from different species (somatic cell hybrids), it was observed that chromosomes of one species can be lost after a series of divisions (Matsuya, Green & Basilico, 1968; Nabholz, Miggiano & Bodmer, 1969; Davidson, 1974). Elimination of chromosomes of one parental species also has been detected in some naturally occurring interspecific hybrids (Schwarzacher & Wachtler, 1983; Fujiwara et al., 1997; Mochida, Tsujimoto & Sasakuma, 2004; Sakai et al., 2007; Ishii et al., 2010) (Fig. 7). In both animals and plants, interspecific hybrids usually die (Coyne & Orr, 1998; Maheshwari & Barbash, 2011). Nevertheless, in the case of plants, such hybrids can be artificially rescued (Kasha & Reinbergs, 1976; Shimizu et al., 1999; Sakai et al., 2007; Houben, Sanei & Pickering, 2011; Yoshikawa et al., 2018). After fertilisation followed by elimination of one parental genome, the plant hybrid embryos must be placed in an artificial growth medium. Later, these embryos can be transplanted to soil where they develop into normal haploid plants but with aberrant meiosis. Therefore, plant breeders use spindle inhibitors (such as colchicine) to induce duplication of the haploid chromosomal set and the formation of diploid organisms (Kasha & Reinbergs, 1976; Forster & Thomas, 2005; Houben et al., 2011).

Elimination of one of the parental genomes occurs during early development and includes gradual chromosomal loss due to lagging in anaphase or the formation of chromosomal bridges (Bennett, Finch & Barclay, 1976; Gernand et al., 2005, 2006; Ishii et al., 2010) (Fig. 7; Table S1). Chromosomes or their fragments may also be eliminated through the budding of micronuclei from the interphase nuclei (Gernand et al., 2005, 2006) (Fig. 7; Table S1).

Selective elimination of one of the parental genomes in interspecific plant hybrids can be considered an example of a postzygotic barrier (Subrahmanyam & Kasha, 1973; Chan, 2011). In this case, only one genome can operate while the other fails to work normally due to cell cycle asynchronisation or centromere dysfunction, and is thus eliminated during early development (Subrahmanyam & Kasha, 1973; Chan, 2011).

Chromosome elimination during clonal and hemiclonal reproduction of animal interspecific hybrids

Selective genome elimination has been observed in interspecific animal hybrids with clonal or hemiclonal reproductive modes (Dawley & Bogart, 1989; Schön et al., 2009; Stenberg & Saura, 2013; Schwander & Oldroyd, 2016; Stöck et al., 2021). One of the parental genomes or some of their parts may be eliminated in the interspecific hybrid during gametogenesis (hybridogenesis) or just after fertilisation (gynogenesis, kleptogenesis, and androgenesis) (Dawley & Bogart, 1989; Schön et al., 2009; Schwander & Oldroyd, 2016; Stöck et al., 2021) (Fig. 8; Table S1). In different hybrid forms, elimination of one of the parental genomes may occur immediately after fertilisation (all gynogenetic fish taxa; mole salamanders from the genus Ambystoma; androgenetic molluscs from the genus Corbicula, and stick insects from the genus Bacillus; gonochoric reduction in triploid carp Carassius gibelio), during mitotic division of germ cells (frogs Pelophylax esculentus, toads Bufo baturae, fish Squalius alburnoides, Poeciliopsis monachal‐lucida, and Bacillus stick insects), or directly during meiosis (loaches Misgurnus anguillicaudatus) (Cimino, 1972; Tunner & Heppich, 1981; Komaru, Kawagishi & Konishi, 1998; Scali et al., 2003; Saitoh, Kim & Lee, 2004; Bogart et al., 2007; Morishima, Yoshikawa & Arai, 2008; Stöck et al., 2012; Zhang et al., 2015; Dedukh et al., 2020) (Fig. 8; Table S1).

Paternal genome, one of the maternal genomes or only some of their parts, are eliminated during kleptogenesis (Bogart et al., 2007). Kleptogenesis is a very old and successful reproductive strategy observed in more than 20 diploid, triploid, and tetraploid hybrids of North American mole salamanders from the genus Ambystoma (Bogart et al., 2007, 2009; Bi & Bogart, 2010; Bogart, 2019). Kleptogenesis includes some still unknown events that result in partial or complete replacement of one of the egg genomes with the sperm genome (Bogart, Elinson & Licht, 1989; Elinson et al., 1992; Bogart et al., 2007; Bogart, 2019) (Fig. 8A; Table S1).

Among asexual vertebrate organisms, gynogenesis is one of the most widespread reproductive modes (Dawley & Bogart, 1989; Schön et al., 2009; Stöck et al., 2021). It relies on the formation of unreduced gametes that are activated by sperm, but do not incorporate sperm genetic material (Dawley & Bogart, 1989; Schön et al., 2009; Neaves & Baumann, 2011; Stenberg & Saura, 2013; Stöck et al., 2021). The sperm pronucleus is usually unable to merge with the female pronucleus and subsequently degrades (Saat, 1991; Neaves & Baumann, 2011; Zhao et al., 2011; Stenberg & Saura, 2013; Zhang et al., 2015) (Fig. 8B; Table S1).

Natural androgenesis is known only in some cypress species (Cypresses), bivalves from the genus Corbicula, and occasionally in some fish species and Bacillus stick insects (Mantovani & Scali, 1992; Tinti & Scali, 1995; Komaru et al., 1998; Komaru, Ookubo & Kiyomoto, 2000; Ishibashi et al., 2003; Wang et al., 2011; Morgado‐Santos et al., 2017). During androgenesis, the maternal genome is eliminated while the paternal genome [or genomes in the case of polyspermy (Mantovani & Scali, 1992; Tinti & Scali, 1995)] continues further development (Komaru et al., 1998, 2000; Ishibashi et al., 2003) (Fig. 8C; Table S1).

Hybridogenetic reproduction includes complete elimination of one parental genome in germline cells, thereby preventing chromosomal conflict during meiosis. Hybridity is restored after crossing such hybrids with complementary parental species (Dawley & Bogart, 1989; Schön et al., 2009; Schmidt et al., 2011; Kimura‐Kawaguchi et al., 2014; Stöck et al., 2021). Thus, hybridogenetic animals are also called ‘gamete parasites’, since they can reproduce with one of the parental species (Schultz, 1969; Tunner, 1973; Mantovani & Scali, 1992; Vrijenhoek, 1994; Schmidt et al., 2011; Unmack et al., 2019; Majtánová et al., 2021). Hybridogenesis has been observed in diploid hybrid fish including livebearers from the genus Poeciliopsis (Schultz, 1967, 1969), carp gudgeons (Hypseleotris) (Schmidt et al., 2011; Majtánová et al., 2021), chub (Squalius) (Carmona et al., 1997) and greenlings (Hexagrammos) (Kimura‐Kawaguchi et al., 2014; Munehara et al., 2016), Bacillus stick insects (Scali et al., 2003), water frogs (Pelophylax) (Tunner, 1973), and triploid hybrid (known as triploid or meiotic hybridogenesis) loaches (Misgurnus) (Morishima et al., 2008), spined loaches (Cobitis) (Saitoh et al., 2004), chub (Squalius) (Alves, Coelho & Collares‐Pereira, 2001; Nabais et al., 2012), green toads (Bufotes) (Stöck et al., 2012) and water frogs (Pelophylax) (Dawley & Bogart, 1989; Vinogradov et al., 1990; Christiansen & Reyer, 2009; Dedukh et al., 2015) (Fig. 8D–F; Table S1).

Selective genome elimination in these organisms allows them to overcome hybrid sterility issues, specifically avoiding the mispairing of chromosomes during meiosis (Dawley & Bogart, 1989; Schön et al., 2009). For some hybrids, genome elimination prevents the acceleration of ploidy level, thus providing normal development after fertilisation (Dawley & Bogart, 1989; Elinson et al., 1992; Schön et al., 2009; Schwander & Oldroyd, 2016).

MECHANISMS OF PROGRAMMED ELIMINATION OF GENETIC MATERIAL

Elimination of genetic material may occur via various mechanisms (Table S1). Organisms can selectively exclude chromosomal fragments, whole chromosomes, or even entire parental genome. Moreover, eliminated sequences can include tandem repeats, mobile elements, and genes (Table S1). The genetic material destined for elimination needs to be recognised and removed appropriately from the nucleus. Elimination is typically accompanied by the epigenetic labelling of selected chromatin, which is especially true in ciliates where epigenetic markers have demonstrated an important role in elimination. In other organisms, the particular role of epigenetic modifications in labelling genomic sequences that should be retained or eliminated remains unknown.

Role of noncoding RNAs in programmed DNA elimination in ciliates

During programmed DNA elimination and rearrangements in ciliates, chromosomes undergo radical reorganisation, including their fragmentation, amplification and the removal of specific genetic sequences (Tobler, 1986; Grishanin et al., 2006; Mochizuki, 2010; Wang & Davis, 2014; Smith et al., 2020). During macronucleus formation, both chromosomal ends and internal eliminated sequences are removed. The remaining chromosomal fragments are re‐ligated to form new chromosomes followed by the addition of new telomeres. Such chromosomes undergo several rounds of endoreplication (Mochizuki et al., 2002; Mochizuki & Gorovsky, 2004; Mochizuki, 2010; Fang et al., 2012). Mechanisms involved in the recognition of eliminated or retained DNA sequences are known only for two classes of ciliates: Oligohymenophorea (Paramecium and Tetrahymena) and Spirotrichea (Euplotes, Oxytricha, and Stylonychia) (Mochizuki et al., 2002; Mochizuki & Gorovsky, 2004; Mochizuki, 2010; Fang et al., 2012; Nekrasova & Potekhin, 2018).

Short noncoding RNAs play a key role in the recognition of specific sequences; however, they act in a completely different way in Oligohymenophorea and Spirotrichea ciliates (Mochizuki & Gorovsky, 2004; Mochizuki, 2010; Fang et al., 2012). In Oligohymenophorea (Paramecium and Tetrahymena), short noncoding RNAs (also known as scanning RNAs or scnRNAs) recognise DNA sequences that should be eliminated from the chromosomes (Mochizuki et al., 2002; Lepère et al., 2008) (Table S1). scnRNAs are initially transcribed in newly formed micronuclei as double‐stranded RNA transcripts that are processed by the Dicer homolog (Mochizuki & Gorovsky, 2004; Malone et al., 2005; Lepère et al., 2009). These scnRNAs are loaded onto Argonaute and move to the old macronucleus (Noto et al., 2010). In the old macronucleus, the scnRNA pool becomes saturated by scnRNAs that complement the eliminated sequences in the genome (Mochizuki, 2010). After the saturation stage, scnRNAs move to new macronuclei where they mark the homologous sequences and attract histone methyltransferases, causing heterochromatin formation in these regions via H3K9me3 and H3K27me3 marks (Liu, Mochizuki & Gorovsky, 2004; Liu et al., 2007; Mochizuki, 2010) (Table S1). Finally, piggyBac transposase‐related proteins recognise the heterochromatin regions and cut them out (Baudry et al., 2009; Cheng et al., 2010).

In contrast to their role in Oligohymenophorea ciliates, short noncoding RNAs distinguish the retained sequences in Spirotrich ciliates (Fang et al., 2012). Moreover, in Euplotes crassus, Oxytricha trifallax, and Stylonychia lemnae, recognition is implemented by another type of short noncoding RNAs, namely Piwi‐interacting RNAs (piRNAs) which interact with Piwi proteins (Fang et al., 2012; Yerlici & Landweber, 2014) (Table S1). The piRNA subclass is abundant in the animal germline and is responsible for retrotransposon silencing (Carmell et al., 2007; Brennecke et al., 2008). In E. crassus, O. trifallax, and S. lemnae, piRNA precursors are formed in the old macronucleus during conjugation (Fang et al., 2012). After processing, piRNAs move to the new macronucleus and mark the sequences of protein‐coding and RNA genes that should be retained; the unmarked sequences become methylated on cytosine residues (Fang et al., 2012; Bracht, 2014; Yerlici & Landweber, 2014). Finally, the unmarked sequences are cut off using numerous domesticated transposases (Nowacki et al., 2009; Fang et al., 2012; Yerlici & Landweber, 2014) (Table S1). After RNA‐mediated elimination of DNA sequences in the developing macronucleus, the remaining fragments undergo massive rearrangements including inversions and translocations to produce functional genes in a process known as unscrambling (Prescott, 1999; Chen et al., 2014). Moreover, long‐noncoding RNAs derived from the paternal macronucleus serve as a template for guiding DNA unscrambling (Nowacki et al., 2009).

Cellular and molecular processes accompanying programmed DNA elimination in multicellular organisms

In other organisms with programmed DNA elimination, including nematodes, the relationship between noncoding RNAs and recognition of eliminated sequences has not yet been established. In nematodes, detailed transcriptome analysis of germ and somatic cells allowed the description of different noncoding RNA classes; but their role in programmed DNA elimination remains unknown (Wang et al., 2011). Cellular processes accompanying programmed DNA elimination have been described in other species. In copepod (Beermann, 1977; Rasch & Wyngaard, 2008; Clower et al., 2016), nematode (Tobler, 1986; Tobler et al., 1992; Müller & Tobler, 2000), and lamprey (Timoshevskiy et al., 2016, 2019) species, DNA elimination can be observed morphologically during mitosis when eliminated chromatin remains in the cell equator after chromosomes have segregated to daughter cells (Fig. 2A, B; Table S1). However, DNA recognition and cutting are thought to occur during the interphase which precedes eliminating mitosis (Tobler, 1986; Magnenat, Tobler & Müller, 1999; Akifyev & Grishanin, 2005; Wang et al., 2020).

In nematodes, eliminated regions exhibit abnormal chromatin condensation and have more accessible chromatin structure but chromatin is not enriched by histone modifications, such as H3K4me3, H3K36me3, H4K20me1, H3K27me3, H3K9me2 and H3K9me3 (Goday et al., 1992; Niedermaier & Moritz, 2000; Wang et al., 2017) (Table S1). Moreover, in nematodes, eliminated regions of their holocentric chromosomes do not accumulate centromeric CENP‐A histone and do not form kinetochores, which leads to their inability to attach to the mitotic spindle (Kang et al., 2016) (Table S1). Analysis of genomes in germline and somatic cells in different parasitic nematodes with programmed DNA elimination showed that regions of chromosomal breaks are not well conserved among different species and depend strongly on species divergence (Bachmann‐Waldmann et al., 2004; Wang et al., 2017). Moreover, chromosomal breakage does not depend on sequence motifs or structure of specific sequences (Wang et al., 2017). Such chromosomal breaks occur randomly within 3–6 kb regions and healing of the breaks occurs by telomere addition (Wang et al., 2017). After elimination, fragments remain in the cytoplasm, are enclosed into micronuclei and degrade while the other chromosomes are successfully separated (Goday et al., 1992; Niedermaier & Moritz, 2000; Wang et al., 2020).

In the genus Cyclops (Copepoda), the removal of chromosomal fragments including interstitial ones does not increase chromosomal number (Beermann, 1977; Grishanin & Akif'ev, 1993). Eliminated DNA forms circular structures enclosed in granules where it is subsequently degraded (Beermann & Meyer, 1980; Grishanin & Akif'ev, 1993; Grishanin & Zagoskin, 2018). Based on these observations, researchers have suggested a model of DNA elimination in Cyclops species (Beermann & Meyer, 1980). DNA sequences destined for elimination are looped out of the chromosomes, excited and then ligated to form a circle, while the remaining chromosomal fragments re‐join together (Beermann & Meyer, 1980; Grishanin & Akif'ev, 1993; Grishanin & Zagoskin, 2018). Interestingly, in lampreys, heterochromatin modifications (5meC, H3K9me3) accumulate in the eliminated regions of chromosomes and in micronuclei comprised of eliminated chromatin (Timoshevskiy et al., 2016) (Table S1). The eliminated chromatin is enclosed in micronuclei, and subsequently degraded in the cytoplasm (Timoshevskiy et al., 2016).

B or sex chromosomes are eliminated through chromosomal lagging

Whole chromosome elimination is usually mediated by centromere malfunction, causing inability to attach to the spindle and lag during anaphase of mitosis or meiosis (Goday & Esteban, 2001; Burt & Trivers, 2009; Schoenmakers et al., 2010; Escribá, Giardini & Goday, 2011; Jones, 2012; Staiber, 2012, 2014). In Aegilops speltoides (goatgrass), B chromosomes are eliminated from roots via nondisjunction during mitosis and lag during anaphase (Ruban et al., 2020). However, in some species, the elimination of chromosomes is characterised by additional epigenetic modifications during certain stages of development (Goday & Esteban, 2001; Schoenmakers et al., 2010; Escribá et al., 2011; Staiber, 2012).

The germline restricted chromosome (GRC), found in songbirds, is one of the best studied examples of elimination of supernumerary chromosomes (Fig. 3D, E; Table S1). Before elimination in both zebra finch (Taeniopygia guttata) and Bengalese finch (Lonchura domestica) males, GRC accumulates histone modifications, such as H3K9me2 and H3K9me3 and, at least in the zebra finch, GRC becomes hypermethylated on histone H4K20 during early meiotic prophase (Goday & Pigozzi, 2010; Schoenmakers et al., 2010; Del Priore & Pigozzi, 2014). In meiotic prophase, the GRC showed a decreased number of RAD51 (radiation‐repair protein 51) and γH2AX (phosphorylated on serine 139 histone H2AX) foci as well as weaker TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining compared to other chromosomes, suggesting a low level of double‐strand break formation on this chromosome. At leptotene and pachytene, GRC becomes intensively acetylated on histone H4K16 and shows strong association with SUMO (small ubiquitin‐related modifier‐1) and HP1 (heterochromatin protein 1) proteins. These epigenetic marks maintain until metaphase I. In the late prophase and metaphase I, GRC accumulates hypophosphorylated histone Н3S10 and ubiquitylated histone H2AK119 and exhibits failure of loading of INCENP (inner centromeric protein). It was suggested that these epigenetic modifications can cause kinetochore and/or centromere malfunction (Goday & Pigozzi, 2010; Schoenmakers et al., 2010; Del Priore & Pigozzi, 2014) (Table S1). Histone phosphorylation at H3S10 and H3S28 during mitosis and meiosis is closely linked to chromosome condensation and is mediated by Aurora B kinase (Giet & Glover, 2001; Goto et al., 2002). It appears that the GRC cannot attach to the microtubules of the spindle during metaphase of the first meiotic division (Schoenmakers et al., 2010; Del Priore & Pigozzi, 2014). After elimination, the GRC forms a micronucleus, which is actively stained by TUNEL, suggesting intensive DNA fragmentation followed by degradation (Pigozzi & Solari, 1998; Goday & Pigozzi, 2010; Schoenmakers et al., 2010; Del Priore & Pigozzi, 2014) (Table S1).

Morphologically distinct condensation has been observed during chromosome elimination from somatic cells in Sciara fungus gnats (Sciaridae, Diptera) and in the midge Acricotopus lucidus (Cecidomyiidae, Diptera) (Perondini & Ribeiro, 1997; Staiber, 2006) (Table S1). In Sciara fungus gnats, phosphorylation of H3S10 in chromosomes occurs normally during mitotic prophase; however, eliminating chromosomes show abnormalities in H3S10 dephosphorylation during late metaphase (Escribá & Goday, 2013). In normal cells, dephosphorylation of H3S10 and H3S28 accompanies sister chromatid separation and causes Aurora B dissociation from metaphase chromosomes (Adams et al., 2001; Goto et al., 2002) (Table S1). Thus, H3S10 and H3S28 dephosphorylation only takes place in the retained chromosomes, but not in the eliminated ones, leading to their proper segregation in contrast to eliminated chromosomes (Escribá & Goday, 2013) (Figs 3B, 4A). Aberrant chromatid separation has also been reported for the eliminated additional chromosomes in A. lucidus (Cecidomyiidae) (Staiber, 2006) (Table S1).

In Sciara fungus gnats, elimination of supernumerary and paternal sex chromosomes occurs not only via lagging during cell divisions in somatic cells but also via micronucleus budding in germ cells (Goday & Esteban, 2001) (Figs 3C, 4B; Table S1). In germ cells, one of the two paternal X chromosomes and some L chromosomes are semicondensed and hence, are morphologically visible, resembling prometaphase chromosomes; however, the other chromosomes are fully decondensed. During elimination, one of the semicondensed chromosomes is connected to the nuclear membrane (presumably via the lamin B receptor) and extruded from the nucleus to the cytoplasm via bud formation (Perondini & Ribeiro, 1997).

Sex chromosome inactivation and heterochromatinisation is known in many species including marsupials. However, in some marsupials, one of the sex chromosomes (usually the paternal chromosome) is eliminated from the somatic cells (reviewed in: Deakin et al., 2009; Smith et al., 2020) (Fig. 4A; Table S1). Notably, Х chromosome inactivation in all marsupials is not controlled by the long noncoding RNA XIST (X‐inactive specific transcript), unlike in placental mammals (Deakin et al., 2009). Moreover, histone modifications typical for heterochromatin, such as H3K27me3 and Н3K9me2, have not been detected in the inactive X chromosome in somatic cells of marsupials (Kohlmaier et al., 2004; Deakin et al., 2009). Nevertheless, differences in DNA methylation levels were seen in marsupial X chromosomes (Waters et al., 2018). To explain the mechanisms causing elimination of sex chromosomes, a replication delay of the inactive X chromosomes (Johnston et al., 2002) or mitotic errors (Close, 1984) have been suggested.

Inability to form chromosomes during metaphase of mitotic or meiotic division leads to the elimination of paternal chromatin

In various species, paternal genome elimination can occur at different ontogenetic stages. Paternal genome elimination has been observed during early embryonic development from progenitors of germ cells, during germ cell divisions, as well as during meiosis (Herrick & Seger, 1999; Burt & Trivers, 2009; Gardner & Ross, 2014; de la Filia et al., 2015) (Fig. 5A, B). In scale insects (Coccidae, Hemiptera), preliminary heterochromatinisation of the paternal genome precedes its elimination (Brown & Nur, 1964; Nur, 1990; Ross, Pen & Shuker, 2010; Prantera & Bongiorni, 2012). In these animals, paternal chromosomes can be heterochromatinised early in development and eliminated from germ cell genomes during spermatogenesis (e.g. lecanoid and Comstockiella scale insects), or they may be eliminated during early development in males (diaspidid scale insects) (Brown & Nur, 1964; Nur, 1990; Ross et al., 2010) (Fig. 5A, B; Table S1). In male embryos of species with embryonic (diaspidid) elimination, paternal chromatids fail to disjoin during early‐cleavage divisions (Herrick & Seger, 1999) (Table S1). Paternal chromosomes are eliminated due to lagging during anaphase (Fig. 5A). If a paternal chromosome escapes elimination during mitosis, it remains condensed until the next one, when it is eliminated (Brown, 1965). In lecanoid scale insects, before elimination, paternal chromosomes accumulate epigenetic markers typical of heterochromatin, such as H3K9me3, H4K20me3, and HP1‐related proteins (Bongiorni et al., 2007; Prantera & Bongiorni, 2012). During inverted meiosis in males of the citrus mealybug Planococcus citri (Coccidae, Hemiptera), both maternal and paternal chromosomes are sorted non‐randomly through a monopolar spindle (Bongiorni et al., 2004). As a result, spermatids with only maternally derived euchromatic chromosomes continue to develop while those with paternally derived heterochromatic chromosomes degenerate (Bongiorni et al., 2004).

Accumulation of epigenetic modifications in maternal and paternal genomes has been observed in Liposcelis booklice (Psocodea) and Sciara fungus gnats (Sciaridae, Diptera) (Goday & Ruiz, 2002; Greciano & Goday, 2006; Hodson et al., 2017) (Table S1). In Sciara fungus gnats, during early germ cell development, paternal chromosomes are known to accumulate H3K9ac, H3K14ac, H4K8ac, and H4K12ac, whereas maternally derived chromosomes exhibit the accumulation of H3K4me2 and H3K4me3. However, during gonial cell multiplication, the opposite epigenetic markers are seen (Goday & Ruiz, 2002; Greciano & Goday, 2006). Such epigenetic states of paternal chromosomes are maintained until meiosis, when the paternal chromosomes are eliminated (Esteban et al., 1997; Goday & Ruiz, 2002; Greciano & Goday, 2006). The paternal genome is eliminated at once via the formation of a monopolar spindle (Fig. 5C). This elimination is accompanied by abnormal Н3S10 dephosphorylation, causing the inability of paternal chromosomes to segregate during anaphase and telophase (Escribá et al., 2011). Thus, only maternal chromosomes are able to attach to the spindle and segregate properly (Esteban et al., 1997; Goday & Esteban, 2001).

Aberrant decondensation of sperm chromatin caused by PSR and Wolbachia

Failure of paternal chromatin decondensation after fertilisation has been observed in organisms that either have a special В chromosome called PSR or are infected with the bacterium Wolbachia (Reed & Werren, 1995; Herrick & Seger, 1999; van Vugt et al., 2003; Werren et al., 2008) (Fig. 6; Table S1). During the first zygotic division, sperm chromatin from males with the PSR chromosome remains compact (van Vugt et al., 2003). Phosphorylation of histone H3 and condensin proteins, which ensure formation of metaphase chromosomes, were not detected in the sperm chromatin (Swim et al., 2012). Their absence results in the inability of paternal chromatin to form metaphase chromosomes, thus causing elimination of paternal chromatin during the first zygotic division (Swim et al., 2012) (Fig. 6A). Only maternal chromosomes, therefore, remain in the egg, leading to haploid organisms that eventually develop into males (van Vugt et al., 2003, 2011; Swim et al., 2012). PSR avoids this elimination by escaping from the compact paternal chromatin to the maternal chromatin (van Vugt et al., 2003, 2011; Swim et al., 2012). Abnormal behaviour of the paternal chromatin has been suggested to be triggered by epigenetic modifications established by the PSR chromosome during male gametogenesis (Werren & Stouthamer, 2003; Swim et al., 2012). One such possible modification is cytosine methylation, which is detected in the paternal genome during spermatogenesis only in males with the PSR chromosome (Aldrich et al., 2017). Moreover, active transcription of the PSR chromosome was detected during male gametogenesis (Akbari et al., 2013; Aldrich & Ferree, 2017). A PSR‐linked gene called haploidizer expressed during testis development may have a potential role of tagging the paternal chromatin (Dalla Benetta et al., 2020).

During Wolbachia infection, which causes cytoplasmic incompatibility, sperm chromatin remains compact and unable to decondense (Tram et al., 2003, 2006) (Fig. 6B; Table S1). Protamine removal from sperm occurs normally; however, the uploading of histone Н3 is prevented (Landmann et al., 2009). As a result, only maternal chromosomes form normally and segregate during anaphase; the paternal genome remains diffuse and lags during anaphase (Landmann et al., 2009; Riparbelli et al., 2012). A recent study has shown that Wolbachia‐expressed deubiquitinases can affect the function of several proteins involved in nuclear import and protamine histone exchange (Beckmann et al., 2019; Chen et al., 2019). Interestingly, if Wolbachia is present, the PSR chromosome is eliminated along with the paternal genome (Reed & Werren, 1995; Werren & Stouthamer, 2003).

Chromosome lagging and micronuclei formation during genome elimination in plant hybrids

Selective elimination of one of the parental genomes is frequently observed in somatic cell hybrids and interspecific plant hybrids. Such elimination occurs during early development and includes sequential chromosomal loss via lagging in anaphase (Bennett et al., 1976; Gernand et al., 2005, 2006; Houben et al., 2011; Sanei et al., 2011) (Fig. 7). Elimination of one of the parental genomes results in haploid plant formation. Nevertheless, the ‘rescue’ of such plants can be achieved using artificial manipulations and treatment with microtubule polymerisation inhibitors to restore the diploid chromosomal set, leading to normal diploid non‐hybrid organisms (Kasha & Reinbergs, 1976; Forster & Thomas, 2005; Gernand et al., 2006; Ravi & Chan, 2010; Houben et al., 2011).

In interspecific plant hybrids, chromosomal lagging can be caused by differences in the timing of crucial mitotic processes, chromosome nondisjunction, which prevents the correct separation of chromatids, or parent‐specific centromere malfunction (Mochida et al., 2004; Gernand et al., 2006; Ishii et al., 2010, 2015, ; Sanei et al., 2011). In unstable wheat (Triticum aestivum) × pearl millet (Pennisetum glaucum) hybrid embryos, cohesin bound to the pearl millet chromosomes possibly cannot dissociate normally during cell division, leading to chromosome nondisjunction (Mochida et al., 2004; Ishii et al., 2010). The specific role of centromeres in selective parental genome elimination has been observed in certain plant species (Ravi & Chan, 2010; Houben et al., 2011; Sanei et al., 2011). In hybrids between two barley species Hordeum vulgare and H. bulbosum, centromeric histone CENH3 preferentially uploads to the chromosomes of H. vulgare, but not H. bulbosum, causing failure of centromere function in the latter (Sanei et al., 2011) (Table S1). During early embryonic divisions, genome elimination was not observed, possibly due to residual gamete‐derived H. bulbosum CENH3, which provides kinetochore function for the H. bulbosum chromosomes. When the amount of gamete‐derived CENH3 falls below a critical threshold, the H. bulbosum chromosomes fail to segregate and are eliminated (Sanei et al., 2011). Interestingly, in H. vulgare × H. bulbosum, chromosome elimination is temperature dependent (Pickering, 1985; Sanei et al., 2011). Sanei et al. (2011) suggested that chaperone proteins can mediate the elimination of H. bulbosum chromosomes; however, the process still requires detailed examination (Table S1).

In addition to chromosomal lagging, the budding of micronuclei from the interphase nucleus can eliminate one of the parental genomes in interspecific plant hybrids of wheat × pearl millet (Gernand et al., 2005) (Fig. 7; Table S1). Notably, chromatin destined for elimination is spatially separated in the interphase nucleus and localises at the nuclear periphery (Gernand et al., 2005). However, the mechanisms leading to genome recognition, followed by chromatin budding, are still unknown.

Both chromosomal lagging and budding cause micronucleus formation, which subsequently leads to heterochromatin modifications and degradation (Gernand et al., 2005; Sanei et al., 2011). However, rarely, chromosomes enclosed in micronuclei may escape degradation (Tan et al., 2015). Such chromosomes can be rescued through nonhomologous end joining, resulting in restructured chromosomes that can be inherited and contribute to increased genetic variability (Tan et al., 2015).

Different pathways of genome elimination in interspecific animal hybrids

Elimination of genetic material often occurs in natural interspecific hybrids which reproduce via a hemiclonal pathway (Dawley & Bogart, 1989; Schön et al., 2009; Schwander & Oldroyd, 2016; Stöck et al., 2021). However, the specific mechanisms of selective genome elimination in these cases are unknown. Even cytological descriptions of the elimination of genetic material have only been performed for a few hybrid forms (Cimino, 1972; Elinson et al., 1992; Komaru et al., 1998; Zhang, Arai & Yamashita, 1998; Morishima et al., 2008; Neaves & Baumann, 2011; Stenberg & Saura, 2013; Zhang et al., 2015; Dedukh et al., 2020) (Table S1).

During paternal genome elimination in gynogenesis and kleptogenesis, sperm chromatin remains compact, being unable to participate in the first zygotic division (Saat, 1991; Elinson et al., 1992; Zhang et al., 2015) (Fig. 8A, B). Similarly, in Drosophila mutants, in which proteins involved in protamine–histone exchange were affected, sperm chromatin remained compact and underwent subsequent elimination (Loppin, Berger & Couble, 2001; Loppin, Dubruille & Horard, 2015). Homologous proteins involved in protamine–histone exchange were also shown to be inactive in gynogenetic carp (genus Carassius) but active in their biological parents (Zhao et al., 2011). During gonochoristic reduction in gynogenetic carp, the paternal genome was found to decondense, although it was unable to form metaphase chromosomes, thereby indicating that condensation of paternal chromatin is affected. Failure in the formation of metaphase chromosomes leads to the paternal genome lagging during anaphase, and hence, subsequent elimination (Zhang et al., 2015) (Fig. 8B; Table S1).

In interspecific hybrid fishes from the genus Poeciliopsis and triploid loaches M. anguillicaudatus, elimination of one of the parental genomes usually occurs during mitosis or meiosis (Cimino, 1972; Zhang et al., 1998) (Fig. 8E, F; Table S1). Elimination is thought to be related to the inability of chromosomes from one of the parental species to attach to the mitotic or meiotic spindle (Cimino, 1972; Zhang et al., 1998). In hybrid fishes from the genus Poeciliopsis, monopolar mitotic spindles are formed in germline cells, and only maternal chromosomes can attach to the spindle while paternal chromosomes remain in the cytoplasm (Cimino, 1972). Lagging chromosomes are destined for subsequent degradation (Cimino, 1972; Zhang et al., 1998).

Interestingly, in water frog hybrids from the genus Pelophylax and carp gudgeons from the genus Hypseleotris, elimination of one of the parental genomes occurs gradually during early gametogenesis along with micronucleus formation (Ogielska, 1994; Chmielewska et al., 2018; Dedukh et al., 2019, 2020; Majtánová et al., 2021) (Fig. 8D; Table S1). In water frog hybrids, misaligned and lagging chromosomes have been detected during a series of gonial cell divisions (Ogielska, 1994; Dedukh et al., 2019, 2020). Therefore, elimination of one of the parental genomes presumably occurs due to the inability of individual chromosomes to attach to the spindle (Ogielska, 1994; Dedukh et al., 2019, 2020). Eliminated chromosomes are enclosed in micronuclei, which accumulate heterochromatin marks and are subsequently degraded via autophagy (Chmielewska et al., 2018). However, micronucleus formation via budding from the interphase nucleus has also been observed in germline cells of water frog hybrids (Chmielewska et al., 2018).

CONCLUSIONS

(1) Eliminated genetic material may include chromosomal fragments, whole chromosomes, and even whole parental genomes. Selective elimination of genetic material includes multiple processes that likely evolved independently in different organisms and serve various purposes.

(2) Despite potential differences in mechanisms, selective elimination of genetic material goes through common stages, such as recognition of sequences destined for elimination, epigenetic labelling, spatial separation, physical removal, and final degradation. Elimination often involves the formation of micronuclei, which subsequently are degraded via autophagy. Similar processes involved in programmed DNA elimination include its initial sequence‐specific recognition possibly via RNA‐dependent mechanisms (scnRNA‐ and piRNA‐dependent elimination in Oligohymenophorea and Spirotrichea ciliates) and tagging of recognised DNA regions via heterochromatinisation (DNA methylation and histone modifications).

(3) The removal of sequences is mediated by various mechanisms and usually occurs during mitotic or meiotic divisions; in rare cases, removal of genetic sequences can also occur during interphase. Selective cutting of DNA at specific sites was observed during chromatin diminution. Elimination of whole chromosomes and even whole genomes presumably occurs due to failure of the eliminated chromosomes to attach to the spindle or errors in chromatid segregation. These abnormalities result in chromosomal lagging during anaphase. Chromosome elimination can also occur via budding from the interphase nucleus. It results in the enclosure of a portion of chromatin or whole chromosomes in micronuclei, accumulation of double‐strand breaks, and subsequent degradation.

(4) Although many questions in the study of the programmed elimination of genetic material remain unanswered, it is clear that programmed DNA elimination is important for genome plasticity and this may open up new possibilities in research into selection, agriculture, and chromosome or genome editing.

Table S1. Summary of programmed DNA elimination in eukaryotes, the processes involved, their role, distribution among species, ontogenetic stages, types of sequences eliminated and mechanisms of elimination.

Click here for additional data file.