Unconventional conservation reveals structure-function relationships in the synaptonemal complex

Abstract

Functional requirements constrain protein evolution, commonly manifesting in conserved primary 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) aligns parental chromosome pairs and regulates exchanges between them. In electron micrographs of meiocytes from all eukaryotic clades, the SC appears as a ~100 nm-wide ladder-like structure with regular striations. Despite the conserved ultrastructure and functions, the proteins that make up the SC are highly divergent in sequence. Here we found that, within the Caenorhabditis genus, SC proteins are significantly more diverged than other proteins. However, SC proteins have highly conserved protein length and coiled-coil domain structure. The same unconventional conservation signature holds true for SC proteins in Drosophila and mammals, suggesting it could be a universal feature of SC proteins. We used this evolutionary signature to identify a novel SC protein in the nematode Pristionchus pacificus, Ppa-SYP-1, which has no significant homology to any protein outside of Pristionchus. Our work suggests that the length and relative arrangement of coiled-coils play a key role in the structure and function of the SC. Furthermore, our analysis implies that expanding sequence analysis beyond measures of per-site identity or similarity can enhance our understanding of protein evolution and function.

Analysis of meiosis in Pristionchus pacificus reveals plasticity in homolog pairing and synapsis in the nematode lineage

“…We inserted an HA epitope tag at the C-terminus of the endogenous coding sequence, and found that immunofluorescence with an epitope-specific antibody localized specifically between paired meiotic chromosomes, confirming SYP-4::HA as a useful marker for the SC (Figure 3A, B). A likely P. pacificus ortholog of C. elegans SYP-1 has also recently been identified, and an epitope-tagged allele displays an identical dynamic distribution (Kursel et al, 2021). The tagged SYP-4::HA protein supports normal meiosis, as indicated by the low percentage of inviable embryos and males among the progeny of homozygotes (Figure 3 -Supplement 1).…”