Unconventional Conservation Reveals Structure-function Relationships in the Synaptonemal Complex

Overview

Journal Elife

Specialty Biology

Date 2021 Nov 17

PMID 34787570

Citations 14

Authors

Lisa E Kursel

Henry D Cope

Ofer Rog

Affiliations

Soon will be listed here.

Abstract

Functional requirements constrain protein evolution, commonly manifesting in a conserved amino acid sequence. Here, we extend this idea to secondary structural features by tracking their conservation in essential meiotic proteins with highly diverged sequences. The synaptonemal complex (SC) is a ~100-nm-wide ladder-like meiotic structure present in all eukaryotic clades, where it aligns parental chromosomes and regulates exchanges between them. Despite the conserved ultrastructure and functions of the SC, SC proteins are highly divergent within . However, SC proteins have highly conserved length and coiled-coil domain structure. We found the same unconventional conservation signature in and mammals, and used it to identify a novel SC protein in , Ppa-SYP-1. Our work suggests that coiled-coils play wide-ranging roles in the structure and function of the SC, and more broadly, that expanding sequence analysis beyond measures of per-site similarity can enhance our understanding of protein evolution and function.

Citing Articles

The synaptonemal complex aligns meiotic chromosomes by wetting.

Gordon S, Rodriguez A, Gu Y, Corbett K, Lee C, Rog O Sci Adv. 2025; 11(9):eadt5675.

PMID: 40009663 PMC: 11864179. DOI: 10.1126/sciadv.adt5675.

Diversification and recurrent adaptation of the synaptonemal complex in Drosophila.

Zakerzade R, Chang C, Chatla K, Krishnapura A, Appiah S, Zhang J PLoS Genet. 2025; 21(1):e1011549.

PMID: 39804957 PMC: 11761671. DOI: 10.1371/journal.pgen.1011549.

Setdb1 and Atf7IP form a hetero-trimeric complex that blocks Setdb1 nuclear export.

Kariapper L, Marathe I, Niesman A, Suino-Powell K, Chook Y, Wysocki V bioRxiv. 2025; .

PMID: 39764026 PMC: 11703210. DOI: 10.1101/2024.12.23.630145.

The structural role of Skp1 in the synaptonemal complex is conserved in nematodes.

Kursel L, Goktepe K, Rog O Genetics. 2024; 228(3).

PMID: 39293001 PMC: 11538402. DOI: 10.1093/genetics/iyae153.

The synaptonemal complex aligns meiotic chromosomes by wetting.

Gordon S, Rodriguez A, Gu Y, Corbett K, Lee C, Rog O bioRxiv. 2024; .

PMID: 39149313 PMC: 11326210. DOI: 10.1101/2024.08.07.607092.

References

Kouznetsova A, Benavente R, Pastink A, Hoog C . Meiosis in mice without a synaptonemal complex. PLoS One. 2011; 6(12):e28255. PMC: 3229524. DOI: 10.1371/journal.pone.0028255. View

Newton J, Naik M, Li G, Murphy E, Fawzi N, Sedivy J . Phase separation of the LINE-1 ORF1 protein is mediated by the N-terminus and coiled-coil domain. Biophys J. 2021; 120(11):2181-2191. PMC: 8390800. DOI: 10.1016/j.bpj.2021.03.028. View

Smolikov S, Schild-Prufert K, Colaiacovo M . A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis. PLoS Genet. 2009; 5(10):e1000669. PMC: 2742731. DOI: 10.1371/journal.pgen.1000669. View

Rillo-Bohn R, Adilardi R, Mitros T, Avsaroglu B, Stevens L, Kohler S . Analysis of meiosis in reveals plasticity in homolog pairing and synapsis in the nematode lineage. Elife. 2021; 10. PMC: 8455136. DOI: 10.7554/eLife.70990. View

Li P, Banjade S, Cheng H, Kim S, Chen B, Guo L . Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012; 483(7389):336-40. PMC: 3343696. DOI: 10.1038/nature10879. View

Cooper J, Phadnis N . Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels. Genome Biol Evol. 2017; 9(7):1938-1949. PMC: 5553355. DOI: 10.1093/gbe/evx131. View

Kumar S, Stecher G, Li M, Knyaz C, Tamura K . MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol. 2018; 35(6):1547-1549. PMC: 5967553. DOI: 10.1093/molbev/msy096. View

Woodruff J . Assembly of Mitotic Structures through Phase Separation. J Mol Biol. 2018; 430(23):4762-4772. DOI: 10.1016/j.jmb.2018.04.041. View

MOSES M, Russel L, Cacheiro N . Mouse chromosome translocations: visualization and analysis by electron microscopy of the synaptonemal complex. Science. 1977; 196(4292):892-4. DOI: 10.1126/science.870966. View

10.

Kumar S, Stecher G, Peterson D, Tamura K . MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis. Bioinformatics. 2012; 28(20):2685-6. PMC: 3467750. DOI: 10.1093/bioinformatics/bts507. View

11.

LARKIN M, Blackshields G, Brown N, Chenna R, McGettigan P, McWilliam H . Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21):2947-8. DOI: 10.1093/bioinformatics/btm404. View

12.

Ollinger R, Alsheimer M, Benavente R . Mammalian protein SCP1 forms synaptonemal complex-like structures in the absence of meiotic chromosomes. Mol Biol Cell. 2004; 16(1):212-7. PMC: 539165. DOI: 10.1091/mbc.e04-09-0771. View

13.

Sohn J, Nam J . The present and future of de novo whole-genome assembly. Brief Bioinform. 2016; 19(1):23-40. DOI: 10.1093/bib/bbw096. View

14.

Page S, Hawley R . The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol. 2004; 20:525-58. DOI: 10.1146/annurev.cellbio.19.111301.155141. View

15.

Johnston S, Huisman J, Pemberton J . A Genomic Region Containing and Is Associated with Individual Recombination Rate Variation in a Wild Population of Red Deer (). G3 (Bethesda). 2018; 8(7):2265-2276. PMC: 6027875. DOI: 10.1534/g3.118.200063. View

16.

MOSES M . Chromosomal structures in crayfish spermatocytes. J Biophys Biochem Cytol. 1956; 2(2):215-8. PMC: 2223961. DOI: 10.1083/jcb.2.2.215. View

17.

Podlaha O, Webb D, Tucker P, Zhang J . Positive selection for indel substitutions in the rodent sperm protein catsper1. Mol Biol Evol. 2005; 22(9):1845-52. PMC: 1351353. DOI: 10.1093/molbev/msi178. View

18.

Podlaha O, Zhang J . Positive selection on protein-length in the evolution of a primate sperm ion channel. Proc Natl Acad Sci U S A. 2003; 100(21):12241-6. PMC: 218743. DOI: 10.1073/pnas.2033555100. View

19.

Carpenter A . Electron microscopy of meiosis in Drosophila melanogaster females. I. Structure, arrangement, and temporal change of the synaptonemal complex in wild-type. Chromosoma. 1975; 51(2):157-82. DOI: 10.1007/BF00319833. View

20.

Hitchcock-DeGregori S . Tropomyosin: function follows structure. Adv Exp Med Biol. 2009; 644:60-72. DOI: 10.1007/978-0-387-85766-4_5. View