Protein Complexes Form a Basis for Complex Hybrid Incompatibility

Abstract

Proteins are the workhorses of the cell and execute many of their functions by interacting with other proteins forming protein complexes. Multi-protein complexes are an admixture of subunits, change their interaction partners, and modulate their functions and cellular physiology in response to environmental changes. When two species mate, the hybrid offspring are usually inviable or sterile because of large-scale differences in the genetic makeup between the two parents causing incompatible genetic interactions. Such reciprocal-sign epistasis between inter-specific alleles is not limited to incompatible interactions between just one gene pair; and, usually involves multiple genes. Many of these multi-locus incompatibilities show visible defects, only in the presence of all the interactions, making it hard to characterize. Understanding the dynamics of protein-protein interactions (PPIs) leading to multi-protein complexes is better suited to characterize multi-locus incompatibilities, compared to studying them with traditional approaches of genetics and molecular biology. The advances in omics technologies, which includes genomics, transcriptomics, and proteomics can help achieve this end. This is especially relevant when studying non-model organisms. Here, we discuss the recent progress in the understanding of hybrid genetic incompatibility; omics technologies, and how together they have helped in characterizing protein complexes and in turn multi-locus incompatibilities. We also review advances in bioinformatic techniques suitable for this purpose and propose directions for leveraging the knowledge gained from model-organisms to identify genetic incompatibilities in non-model organisms.

A Lethal Genetic Incompatibility between Naturally Hybridizing Species in Mitochondrial Complex I

“…We identified a mitonuclear incompatibility that involves at least three genes and causes hybrid lethality in lab and wild populations. Theory predicts that hybrid incompatibilities involving multiple genes should be common (6,7), but with few exceptions (8,(12)(13)(14), they remain virtually uncharacterized at the genic level (6). Moreover, we show that there has been exceptionally rapid evolution in both mitochondrial and interacting nuclear genes in X. birchmanni, which may have introduced mutations that are incompatible in hybrids (Fig.…”

“…The copyright holder for this preprint (which this version posted July 14, 2021. ; https://doi.org/10.1101/2021.07.13.452279 doi: bioRxiv preprint genic level (6). Moreover, we show that there has been exceptionally rapid evolution in both mitochondrial and interacting nuclear genes in X. birchmanni, which may have introduced mutations that are incompatible in hybrids (Fig.…”

“…We identified a mitonuclear incompatibility that involves at least three genes and causes hybrid lethality in lab and wild populations. Theory predicts that hybrid incompatibilities involving multiple genes should be common (6,7), but with few exceptions (8,(12)(13)(14), they remain virtually uncharacterized at the . CC-BY 4.0 International license available under a was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

“…As a consequence of this knowledge gap, key predictions about the genetic architecture of hybrid incompatibilities and the evolutionary processes that drive their emergence remain untested. For one, theory suggests that incompatibilities should be more common within dense gene networks, both because the number of potentially incompatible genotypes explodes as the complexity of the genetic interaction increases and because genes involved in such interactions are expected to be tightly co-evolving (6,7). Consistent with this prediction, mutagenesis experiments have highlighted the sensitivity of multi-protein interactions to changes in any of their components (6).…”

“…For one, theory suggests that incompatibilities should be more common within dense gene networks, both because the number of potentially incompatible genotypes explodes as the complexity of the genetic interaction increases and because genes involved in such interactions are expected to be tightly co-evolving (6,7). Consistent with this prediction, mutagenesis experiments have highlighted the sensitivity of multi-protein interactions to changes in any of their components (6). However, genetic interactions are notoriously difficult to detect empirically except in systems with especially powerful genetic tools (8), and this problem is exacerbated with complex genetic interactions (9,10).…”