similarity of domain organization of proteins in phylogenetically distant organisms as a basis of...

1062-3604/04/3506- © 2004

MAIK “Nauka

/Interperiodica”0337

Russian Journal of Developmental Biology, Vol. 35, No. 6, 2004, pp. 337–344. Translated from Ontogenez, Vol. 35, No. 6, 2004, pp. 415–423.Original Russian Text Copyright © 2004 by Bogdanov.

A well known phenomenon of homology of mor-phological features in the organisms of the same taxon,for example, of the same class was in due time esti-mated in terms of phenogenetics (developmental genet-ics). Such an estimate was present in the law of homol-ogous series of variation, which N.I. Vavilov formu-lated in the 1920s and continued to make more preciseand improve for about ten more years. He formulatedthis fundamental biological law on the basis of studiesof plants. Later, he extended this law to the animalworld as well. In one of formulations in 1930, Vavilovdefined the homologous series as “a biological phe-nomenon consisting in that there are repeating, analo-gous, parallel series of forms among different speciesand even genera. i.e., forms similar in their morpholog-ical and physiological features” (Vavilov, 1987).Vavilov wrote in his book

Zakon gomologicheskikhryadov v nasledstvennoi izmenchivosti

(Law of Homol-ogous Series in Hereditary Variation, 3rd ed., 1935) thatthis law is true for larger taxa, families and classes, andgave example of the homology of morphogenetic pro-cesses in ascomycetes and basiodiomycetes, in theclass Infusoria, in fossil cephalopods, in insects,amphibians, and mammals (Vavilov, 1987).

In all these cases, homology was deduced from thesimilarity of variation of features and namely, discretechanges that formed series. This description of the fun-damental phenomenon of homology implied thehomology of genes.

When molecular genetics appeared, it became pos-sible to study the molecular bases of homologous seriesof variation. Attempts have been undertaken to explainthe homology of morphological features on the basis ofuniversal genetic code (Vorontsov, 1966). But as themolecular structure of genes was deciphered,sequences of nucleotide pairs in DNA, it turned out thatthere is no direct relationship between the primarystructure of DNA and a morphological feature.

The young, but rapidly developing genomics hasalready developed its own understanding of this prob-lem and quantitative estimate of homology. The homol-ogy of genes is considered essential when the sequenceof nucleotide pairs coincides by no less than 80%(Chervitz

et al.

, 1998; Rubin

et al.

, 2000). This homol-ogy is characteristic for the genes encoding function-ally important proteins, specifically for the genesencoding enzymes and is, as a rule, followed within thelimits of a taxonomic class.

Similarity of Domain Organization of Proteinsin Phylogenetically Distant Organisms

as a Basis of Meiosis Conservatism

Yu. F. Bogdanov

Vavilov Institute of General Genetics, Russian Academy of Sciences, ul. Gubkina 3, Moscow, 119991 RussiaE-mail: [email protected]

Received March 29, 2004

Abstract

—The cytological mechanism of meiosis is very conservative in all eukaryotes. Some meiosis-specificstructural proteins of yeast, nematode

Caenorhabditis elegans

,

Drosophila

, and mammals, which play identicalroles in cells during meiosis, do not have homology of the primary structure, but their domain organization andconformation are similar. The enzymes of meiotic recombination in yeast and plants have similar epitopes.These facts suggest that the similarity of the higher level of organization of the meiosis-specific proteins allowsthese proteins to form similar subcellular structures and produce similar cytological picture of meiosis and sim-ilar functions of these subcellular structures. Finally, this leads to a conservative scheme of meiosis in evolu-tionally distant eukaryotes.

Key words

: meiosis, genes, mutations, proteins, domains, homology, secondary structure, synaptonemal com-plex.

TO THE CENTENARY OF BORIS L. ASTAUROV

This paper is based on the author’s lecture delivered in mem-ory of B.L. Astaurov on November 13, 2002

“S

implify the complex and you willobtain the most essential result”

Henry Buckle

338

RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY

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BOGDANOV

The homology of proteins, especially those fulfill-ing morphogenetic functions, i.e., “building” proteins,rather than that of genes, is more important for the pur-pose of this paper. Due to the genetic code redundancy,one could expect that the sequences of nucleotides inhomologous genes are more variable than those ofamino acids in the corresponding proteins in variousorganisms.

Of real interest is the question as to how the similar-ity of intracellular structures in taxonomically distantorganisms is ensured at the molecular level. This ques-tion concerns all cell structures: from cytoplasmicmembranes to organelles involved in cell division.

The published data on cytology of meiosis andresults of our own extensive studies of meiosis suggestthat the scheme of meiosis in animals, fungi, and plantsis very conservative, although some details vary. Thereare mutations that change the course of meiosis, includ-ing mutations of specific meiosis genes. Tens of suchgenes have been identified in the most extensively stud-ies model species.

Judging by the data for the best studied model spe-cies, yeast

Saccharomyces cerevisiae

, meiosis shouldbe governed by hundreds of genes, including thosecommon for meiosis and mitosis (common genes ofcell division) and those specific for each of these pro-cesses (Bogdanov, 2003). Table gives an idea about thenumber of already identified specific meiosis genes indifferent species.

The mutations of meiotic genes include phenotypi-cally similar genes in different species. The publisheddata on morphological changes in the picture of meiosisallows us to speak about homologous series of variationin meiotic features in a wide range of taxa, includingthe kingdoms (Bogdanov, 2003). May be, it is morecorrect to speak about homomorphism of these fea-tures. Let us give some examples.

HOMOMORPHISM OF CYTOLOGICAL FEATURES OF MEIOSIS

Mutations

compact chromosomes

were found in thebarley

Hordeum vulgare

(Moh and Nilan, 1954) and

rye

Secale cereale

(Sosnikhina

et al.

, 2004), which leadto the supercondensation of chromosomes at metaphaseI, but are not expressed in somatic cells (Fig. 1). Thecondensation of chromosomes during mitosis and mei-osis depends on specific chromatin proteins, con-densins, and one of these proteins, meiosis-specific,may be affected by the above mentioned mutations. Wewill consider below one of possible proteins—candi-dates for participation in the expression of this muta-tion. The example of mutation

compact chromosomesrefers to

plants of one family, Poacea, but phenotypi-cally similar mutations of meiotic genes have beenidentified in different plant families as well.

Meiosis-specific mutations leading to synapsis ofnonhomologous chromosomes at prophase I werefound in the diploid onion

Allium cepa

(Liliacea)

, dip-loid maize and rye, and hexaploid wheat

Triticum aes-tivum

(all—Poacea). The presence of a gene or genesresponsible for strict homology of synapsis in thehexaploid wheat was considered self-evident, sincegiven three homeologous genomes, AA, BB, and DD,the chromosomes should be protected against nonho-mologous (heterologous) synapsis. But the discovery ofsuch genes in diploid maize, onion, and rye plants(Timofeeva and Golubovskaya, 1991; Jenkins andOkumus, 1992; Fedotova

et al.

, 1994) proved to bevery important. This means that the homologous natureof synapsis is strictly controlled by special genes evenin the diploid set of chromosomes.

There are examples of homomorphism of the cyto-logical features of meiosis in taxonomically very dis-tant species.

From the time of elegant cytological studies of mei-osis carried out in the beginning of the 20th century, itwas known that chromosomes form a figure of bouquetat the early prophase I: the ends of chromosomes aregathered in a bundle on the inner side of nuclear enve-lope, while inner regions of chromosomes form loopswithin the nucleus (Wilson, 1936). In the current terms,this is described as clusterization of the telomereregions of chromosomes on the inner side of the nuclearmembrane (Fig. 2a). It is believed that clusterization oftelomeres on the membrane enhances approach and

Table 1.

Number of specific meiotic genes identified in different species

Species

Number of known meiotic genes

Referencetotal studied at the

molecular level

Yeast

Saccharomyces cerevisiae

~300 ~300 Priming

et al.

, 2000

Fruit fly

Drosophila melanogaster

~120 ~30 Grishaeva and Bogdanov, 2000;Manheim and McKim, 2003

Maize

Zea mays

~30 4–5 Golubovskaya

et al.

, 2002;Pawlovski

et al.

, 2004

Rye

Secale cereale

21 – Sosnikhina

et al.

, 2004

Plant

Arabidopsis thaliana

~20 ~10–12 Jones

et al.

, 2003; Schwarzacher, 2003


Vol. 35

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SIMILARITY OF DOMAIN ORGANIZATION OF PROTEINS 339

synapsis of homologous chromosomes at prophase I(Zickler and Kleckner, 1998). During almost the entire20th century, it was being written in all manuals thatplants, unlike animals and fungi, do not have the “bou-quet” of chromosomes in meiosis, as well as centriolesof polar bodies of spindles. It was believed that theapproach of chromosomes from far away distances atprophase I is ensured by a certain mechanism of syne-sis, compression of chromosomes in a synizetic knot(Rhoades, 1961) and this configuration was consideredas an alternative to the “bouquet” in animals (John,1990). However, when prophase nuclei of meiotic plantcells were examined under an electron microscope withthe help of 3D reconstruction of serial ultrathin section,it turned out clusterization of telomeres on the innerside of the nuclear membrane takes place at the earlyzygotene. The Danish cytologist Holm (1977) was thefirst to describe this phenomenon in

Lilium

. This phe-nomenon was soon found in other plant species (Gil-lies, 1984). In the simplest form, it looks as a bundle oftelomere regions of the synaptonemal complexes on thepreparations of zygotene nuclei destroyed by hypotonicshock and surface-spread (Fig. 2b).

Elegant evidence of the genetic control of formationof this bouquet of chromosomes at the leptotene and

zygotene stages in rye (Mikhailova

et al.

, 2001) andmaize (Golubovskaya

et al.

, 2002) have recently beenobtained. There is also a gene in yeast, which encodesthe protein of telomere regions of the chromosomes.This protein ensures the clusterization of telomereregions of the chromosomes on the inner side of thenuclear membrane at prophase I (Trelles-Sticken

et al.

,2000; cit. from Schertan

et al.

, 2001). Thus, the cluster-ization of chromosomes on the nuclear membrane atthe early prophase I and arising, as a result, the “bou-quet” organization of prophase meiotic chromosomesis present in all kingdoms of eukaryotes and appears tobe an ancient feature of meiosis. This feature was ana-lyzed in detail (Zickler and Kleckner, 1998). This com-plex feature is, in all likelihood, polygenic. I do notknow whether there is a homology of the genes respon-sible for this feature in yeast and higher plants, there-fore one can only say not that these genes are, at leastfunctionally, analogous and lead to homology of thefeature in the Vavilovian sense and that there are muta-tions leading to the identical phonotypical variation ofthis feature. There are also exceptions from the rule ofclusterization of telomeres in meiosis, for example, inflies, including the genus

Drosophila

. These exceptions

(c)

(a)

(d)

(b)

Fig. 1.

Chromosomes in meiosis of normal plants (a, c) and meiotic mutants

compact chromosomes

(b, d) of barley (a, b) and rye(c, d) at the same magnification (Sosnikhina, personal communication) (mutation

compact chromosomes

is also designated as

mei10

). (a, b) stage of diakinesis, (c, d) stage of metaphase I.

340


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BOGDANOV

have corresponding explanations and are discussed sep-arately (Bogdanov, 2003).

Thus, many features of meiosis (expression of spe-cific meiotic genes) in evolutionarily distant speciesobey the Vavilov’s law of homologous series of varia-tion. Does this mean that these meiotic genes arehomologous? It was already mentioned that in terms ofthe modern genomics, the homology is defined ashomology of the primary DNA and protein structure.But such homology is absent in many genes which areexpressed as similar phenotypes in different plants andanimals. These genes encode proteins different in pri-mary structure, but functionally similar.

ANALOGY OF THE FUNCTIONS OF PROTEINS PLAYING MORPHOGENETIC ROLES

The analogy of phenotypes (phenes) can be fol-lowed in distant taxa and at the molecular level. A mei-osis-specific histone was found in

Lilium

plants (Sheri-dan and Stern, 1967; Strokov

et al.

, 1973) and in mice(Meistrich, 1982), and later in other mammals (Fig. 3).It appears in addition to histone H1 and does not makea part of nucleosome structure. It received differentnames: meiotic histone, meiotin, testis-specific histone,etc. The similarity of primary structure of this histonewithin the class Mammalia does not exceed 62%. Thedegree of similarity between this histone and meiosis-specific histone in

Drosophila

and

C. elegans

is evenlower. In invertebrates, even the molecule of this pro-tein is shorter than in mammals, but the function ofthese proteins appears to be identical: they either leadto additional, as compared to mitosis, compactizationof chromatin of the metaphase meiotic chromosomes(Table 2), or are involved in compactization of the syn-aptonemal complexes (SC) (Sheridan and Barnett,1969). If the first suggestion is correct, it cannot beexcluded that the “meiotic histone” is involved in thesupercondensation of chromosomes in the barley andrye meiotic mutants

compact chromosomes

. There isexperimental evidence in favor of this suggestion(Hasenkampf

et al.

, 1998). It may well be that this his-tone not only compactizes chromosomes starting fromthe pachytene stage, but also delays their compactiza-tion at the early leptotene stage making the leptotenechromosomes much longer than the mitotic prophasechromosomes.

(b)

(a)

Fig. 2.

A “bouquet” of synaptonemal complexes and chro-mosomes in animals and plants at the early zygotene stage.(a) An oocyte of diploid

Bombyx mori

(reconstruction ofultrathin sections; axial elements of chromosomes havebeen drawn). Out of 112 ends (telomere regions) of chromo-somes, 102 ends contact with the inner side of the nuclearenvelope in a restricted region and form the base of bou-quet; six ends only begin pair-wise formation of synaptone-mal complexes (after Rasmussen and Holm, 1981). (b) Elec-tron micrograph of a region of the surface-spread microspo-rocyte nucleus of the rye

Secale cereale

spread on asublayer (microspread).

( )

ends of nonpaired axial ele-ments of chromosomes,

(

�

)

ends of synaptonemal com-plexes; all these are aggregated in one area in the periphery of thenucleus, near the bouquet base. All 28 ends of the diploid ryechromosomes can be seen, eight of them participating in the syn-aptonemal complex. Scale: 1

µ

m (after Fedotova, 1989).

1 2 3 4 5 6 7

H3 ox

HMH1

H2

H4

Fig. 3.

Polyacrylamide gel electrophoresis of histones fromleaves and anthers of

Lilium candidum

L. H1,2,4—histones,H3 ox—oxidized form of histone H3; HM—specific his-tone of meiosis; Lanes:

1

, leaves,

2

, mitosing sporogeniccells;

3–6

, microsporocytes synchronously passing throughmeiosis (

3

—early leptotene,

4

—late leptotene,

5

—zygo-tene,

6

—zygotene and pachytene);

7

—young microsporeswith haploid number of chromosomes (after Strokov

et al.

,1973).


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2004


The structural proteins of SCs, skeletal structures ofprophase meiotic chromosomes, are the most interest-ing class of proteins specific for meiosis and involvedin variation of meiotic features. The scheme of SCstructure is similar in protests, fungi, plants, and ani-mals, but its ultrastructural elements are formed by pro-teins different in their primary structure. The primarystructure of these proteins in mouse, hamster, and mancoincides by 60–80%, while in budding yeast and

Drosophila

, it has nothing in common with mammals.

Both in yeast and mammals, SCs are formed bythree major proteins. The key role in synapsis of homol-ogous chromosomes is played by the protein forming a“zipper” between two lateral SC elements, i.e., betweenhomologous chromosomes. Let us call it “synapsis pro-teins” (Fig. 4).

Synapsis proteins have been isolated and exten-sively studied in four mammals (SCP1) and yeast(Zip1). The proteins SCP1 and Zip1 have no homologyin primary structure but have similar structural plansand physicochemical properties (for detail see Heyting,1996; Penkina

et al.

, 2002) and belong to the categoryof intermediate structural proteins. The molecules ofthese proteins contain 870 to 990 amino acid residuesand consist of three domains. Each domain is similar inits secondary and tertiary structures to the correspond-ing domain in similar proteins of other comparedorganisms. The central domain forms

α

-helix which iscapable of superspiralization (coiled-coil).

In vitro

,these proteins form dimers of the molecules arranged inparallel and superspiralization of the central domainsimparts rigidity to these dimmers (Fig. 4). Zipper teethbetween lateral SC elements are formed by such dim-mers SCP1 or Zip1 (Heyting, 1996; Penkina

et al.

,2002) and N-terminal domains are located at the endsof these teeth, which are zippered by means of comple-mentary electrostatic charges (Grishaeva

et al.

, 2004).C-terminal domains of these proteins are basal, whichis essential for interaction with DNA of the lateral SCelements (Penkina

et al.

, 2002).

We found a high correlation between the length ofthe central rod-like domain of these proteins and widthof the SC central space in yeast and mammals, as wellas other similarities between the secondary and tertiarystructures of these proteins (Bogdanov

et al.

, 2002,2003). These correlation and similarities of proteinorganization allowed us to find, using the computermethods, the genes in the fly

Drosophila melanogaster

,plant

Arabidopsis thaliana

, and nematode

Caenorhab-ditis elegans

, whose virtual proteins have predictablesimilar functions: to serve as synaptic proteins(Grishaeva

et al.

, 2001, 2004; Bogdanov

et al.

, 2002,2003). Note that for

Drosophila

, this finding was con-firmed experimentally (Page and Hawley, 2001). Thegene encoding synapsis protein in

Drosophila

provedto be the well known gene

c(3)G

, Gowen’s suppressorof crossingover, whose mutation leads to the failure ofSC formation and complete asynapsis of homologous

chromosomes (Grishaeva

et al.

, 2001; Page and Haw-ley, 2001), like the mutation

zip1

in yeast.A similar coincidence of the functions of the genes

nonhomologous by their primary structures is alsoobserved for suppressors of kinetochore cleavage atmetaphase I of meiosis in yeast and

Drosophila

(fordetail see Bogdanov, 2003). Thus, the analogy of func-tions of the specific structural proteins of meiosis intaxonomically very distant species is determined by theanalogy of conformation of these protein molecules.

Among 40 identified kinetochore proteins of mam-mals and fungi, only few can be considered as evolu-tionarily conservative and essential for the functioningof kinetochores (Cheo, 1997). One of them is the mam-malian protein CENPC. It forms the inner kinetochoresurface exposed to chromatin. The protein Mif2p is itshomolog in yeast. These proteins are very similar, buttheir similarity is restricted to two small blocks ofamino acids (Brown, 1995; Meluh and Koshland,1995). Region I of the protein Mif2p consists of 23 aminoacids and is similar by 43% to the corresponding areain the human protein CENPC, while region II consistsof 52 amino acids and is similar by 29% to the corre-sponding region in human CENPC. There is a temper-ature-sensitive mutation

mif

inside each region, thussuggesting that the conservative area serves as a func-tional domain (Brown, 1995). Both CENPC and Mif2phave characteristics essential for binding to DNA,although no absolutely specific DNA-binding area wasfound. The highest homology of two proteins and theirgenes is expressed in the phenotypes of mutations

cenpc

and

mif2

. Both mutations lead to aberrant segre-gation of chromosomes (Kalitsis

et al.

, 1997; Fuka-

Ch LE

C NN C

Fig. 4.

Schematic diagram of synaptonemal complex (SC).

Ch

, lateral loops of chromatin;

LE

, lateral SC elements(protein axes of homologous chromosomes), C and N, cor-responding ends of protein molecules forming transverse fila-ments (zipper teeth), ( ) central domain of this protein.

Table 2. Chromosome length in mitosis and meiosis I in Li-lium regale as an index of chromosome compactization (afterSax and Sax, 1935)

Mode of cell division

Mean chromosome lengthat the division stage, µm

prophase metaphase

Mitosis in root tips 35 22

Meiosis I in anthers 83 12

342

RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY Vol. 35 No. 6 2004

BOGDANOV

gawa and Brown, 1997) and on this basis and takinginto account all above said, it can be concluded that thehuman protein CENPC and yeast protein Mif2p arehomologous in the Vavilovian sense, since their muta-tional variation leads to similar cell phenotypes. Thisphenomenon probed to be even more significant whena similar protein of the inner surface of kinetochoreswas found in the maize Zea mays L. There are five vari-ants of this protein all having region I of 23 amino acidsat the C-end, which is homologous by 61 and 74% tothe corresponding regions in the yeast protein Mif2pand human protein CENPC, respectively (Dawe et al.,1999). No homology was found in region II. Amongthese five variants, one, CenpcC, was isolated from theanthers at synchronous prophase I of meiosis. It ishomologous by 78−95% to other four variants of pro-teins isolated from 13-day embryos, germinating seeds,young shoots, and young (2-week) leaves and can beconsidered a meiosis-specific proteins. In this case, thespecificity of this protein for meiosis is not significant,while it is more significant that the DNA-bindingregions of all these proteins in yeast, maize, and manhave a high degree of homology. It is significant that inthe course of biological evolution, the nature selectedonly one variant of protein capable of binding to thecentromeric DNA, while the centromeric DNAs ofyeast and mammals have marked differences in theirprimary structures.

The enzymes of meiotic recombination in eukary-otes, such as RecA-like proteins of the family Rad51 infungi and plants, have a high degree of homology intheir primary structures, as follows from immunochem-ical tests. These enzymes are so similar in their molec-ular organization and function in different taxa that theyreceived identical names, for example Rad51 andDmc1 in yeast, higher plants, and mammals. Othermeiosis-specific proteins-enzymes involved in meioticrecombination also function in similar way and are sim-ilarly called: M1h1, Msh4, etc. This is not surprisingsince they are involved in identical processes at themolecular level: formation of DNA heteroduplexes andHoliday structures and their processing during meioticDNA recombination (for detail see Bogdanov, 2003).

The problem of similarities and differences in thestructure and functions of meiosis-specific proteinsrequires special analysis and separate discussion. Thispaper deals with the role of the higher level of organi-zation of the morphogenetic proteins of subcellularstructures and their secondary and tertiary structure(conformation) in the formation and functioning ofthese proteins in eukaryotes from different kingdoms.These are exemplified by proteins of SCs and kineto-chores, subcellular structures fulfilling a key role inmeiosis.

Examples of phenotypic homology of mutations,such as mutation of supercondensation in meiosis, willalso be possibly explained on the basis of similar func-tions of proteins-condensins or meiosis-specific histone

and similar modifications of the structure of these pro-teins as a result of mutations. In any case, we do notknow of any other material basis for explanation of sim-ilar phenotypic expression of these mutations in thebarley and rye on the grounds of current knowledgeabout the molecular organization of chromatin.

The example with analogy of mutations leading toheterologous synapsis of chromosomes in plants alsoindicates to a possible involvement of a certain meiosis-specific protein in this phenomenon.

DEPENDENCE OF ORGANELLE MORPHOLOGY ON PROTEIN STRUCTURE

It is not by chance that in the end of his life, Boris L.Astaurov became concerned with homology of chro-mosome synapsis in meiosis. Earlier, Astaurov experi-mentally produced triploid Bombyx mori males andkindly gave them for studying the SC to the young Dan-ish cytologist S. Rasmussen, who showed that there arethree phases of chromosome synapsis at prophase I ofmeiosis in these triploids (Rasmussen, 1977; Rasmus-sen and Holm, 1981). Initially (first phase), homolo-gous chromosomes synapse and form SCs, but sincetriploids have three sets of such chromosomes,trivalents are formed. This process is accompanied bycompetition for mating partner: if one chromosome isinvolved in synapsis at a certain locus, it becomes a“spoiler” in some other locus and is pushed out from apaired association. At the second phase, pairs of homol-ogous chromosomes are fully rescued from spoilersand the nucleus is devoid of trivalents. Bivalents andunivalents can only be seen. At the third phase, nonho-mologous univalents enter pair-wise synapsis in a ran-dom way. This synapsis is nonhomologous and SCs arealso formed between such nonhomologous chromo-somes. This means that SC can be formed due to self-assembly of proteins, rather than under the control ofpairing of homologous DNA loci. This self-assemblywas demonstrated indirectly (Bogdanov, 1977) anddirectly (Pelttari et al., 2001). This is self-assembly ofprotein structures determined by their secondary andtertiary structures.

In the beginning of the 1970s, Astaurov stated in oneof his lectures that he was very impressed by the dis-covery of SCs. Cytologists observed under a micro-scope a gap between parallel homologous chromo-somes at prophase of meiosis I for a long time andcalled it synaptic gap. It was not clear what happens inthis gap and how chromosomes are kept at a certain dis-tance and preserve this gap between them. The discov-ery of finely structurized SC, as Astaurov said,explained this enigma. I have already tried to explainthe molecular basis of uniformity (evolutionary conser-vatism) of the “construction” of this gap inside SC inevolutionarily distant eukaryotes. And I conclude thatthe similarity of structure and function of the corre-sponding organelles in evolutionarily distant organismsis based on the analogy of conformation of structurally



and functionally significant domains of the proteinsthat form these organelles. Three-dimensional subcel-lular structures are inevitably formed from three-dimensional protein molecules ordered in nanometricspaces and associated in supermolecular complexes.This principle is known in molecular biology for a longtime. I only apply it to the complex and largely enig-matic process of meiosis. Alberts et al. (1986, p. 142)described this principle in the following way: “Theprinciple allowing association of protein domains … isalso “working” during assembly … of cell structures.Supermolecular structures, such as enzyme complexes,ribosomes, protein fibers, viruses, and membranes, arenot synthesized as covalently linked single giant mole-cules, but are associated as a result of covalent aggrega-tions of macromolecular subunits.” In the case of meio-sis, this refers directly to the self-assembly of the struc-turized space of “synaptic gap” between homologousand nonhomologous chromosomes from rod-likedomains of fibrillary proteins SCP1, especially at theRasmussen’s third phase. The construction of largestructures from protein subunits has some advantages.Firstly, less genetic information is required for assem-bly from repeated smaller subunits. Secondly, assemblyand dissociation of subunits are easily controlled, sincethey are interconnected by many relatively weak (non-covalent) bonds. And, in the assembly, the mechanismof correction is formed, which can eliminate defectivesubunits during assembly (Alberts et al., 1986).

These fundamental theses can be used for explana-tion of conservatism of the scheme of meiosis ineukaryotes, which is based on the properties of proteinmolecules and nucleoprotein complexes. Moreover, aswas long ago shown in molecular biology on the exam-ple of self-assembly of viruses and, then, ribosomes, aself-assembling structure can consist of different pro-tein subunits and nucleic acids. Here, I pay specialattention to the fact that the size and 3D structure (con-formation) of individual protein domains can serve as abuilding material for the formation of identical subcel-lular structures in phylogenetically distant organisms,even if the primary structure of these domains markedlydiffers.

ACKNOWLEDGMENTS

The author is grateful to T.M. Grishaeva andS.Ya. Dadashev for cooperation which helped in for-mulation of the concept of this paper.

This study was supported by the Russian Founda-tion for Basic Research, project no. 02-04-48761.

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