Colocality to Cofunctionality: Eukaryotic Gene Neighborhoods as a Resource for Function Discovery

Abstract

Diverging from the classic paradigm of random gene order in eukaryotes, gene proximity can be leveraged to systematically identify functionally related gene neighborhoods in eukaryotes, utilizing techniques pioneered in bacteria. Current methods of identifying gene neighborhoods typically rely on sequence similarity to characterized gene products. However, this approach is not robust for non-model organisms like algae, which are evolutionarily distant from well-characterized model organisms. Here, we utilize a comparative genomic approach to identify evolutionarily conserved Proximal Orthologous Gene (POG) pairs conserved across at least two taxonomic classes of green algae. A total of 317 gene neighborhoods were identified. In some cases, gene proximity appears to have been conserved since before the streptophyte-chlorophyte split, 1,000 million years ago. Using functional inferences derived from reconstructed evolutionary relationships, we identified several novel functional clusters. A putative mycosporine-like amino acid (MAA), “sunscreen”, neighborhood contains genes similar to either vertebrate or cyanobacterial pathways, suggesting a novel mosaic biosynthetic pathway in green algae. One of two putative arsenic-detoxification neighborhoods includes an organoarsenical transporter (ArsJ), a glyceraldehyde 3-phosphate dehydrogenase-like gene, homologs of which are involved in arsenic detoxification in bacteria, and a novel algal-specific phosphoglycerate kinase-like gene (PGK). Mutants of the ArsJ-like transporter and PGK-like genes in Chlamydomonas reinhardtii were found to be sensitive to arsenate, providing experimental support for the role of these identified neighbors in resistance to arsenate. Potential evolutionary origins of neighborhoods are discussed, and updated annotations for formerly poorly annotated genes are presented, highlighting the potential of this strategy for functional annotation.

Genome-wide identification and expression profiling of the COBRA-like genes reveal likely roles in stem strength in rapeseed (Brassica napus L.)

“…The BnaCOBL gene clusters [ 43 – 45 ] containing two or three BnaCOBLs appear on the chromosome A03, C05, C07, C08, and C09 ( Fig 2 ). The cluster on A03, C07, and C09 exhibited the same order on the “X block” [ 46 ] of B .…”

cblaster: a remote search tool for rapid identification and visualisation of homologous gene clusters

“…Complex biological processes are coordinated through the action of multiple distinct, yet functionally associated genes, which are often found physically collocated within genomic neighbourhoods as gene clusters. Gene clusters have been extensively studied in microbes for their ability to encode traits such as the biosynthesis of secondary metabolites, virulence, drug resistance and xenobiotic degradation; however, gene clustering is a phenomenon observed across all kingdoms of life (Chevrette et al 2020;Wang et al 2019;Nützmann et al 2018;Foflonker and Blaby-Haas 2021). Given the relationship between genetic collocation and cofunctionality (Lee 2003;Michalak 2008), it follows that we can detect gene clusters by directly searching for conserved instances of collocation across taxa.…”

Automatic Gene Function Prediction in the 2020’s

“…Proximity between genes has also been shown to be indicative of co-functionality [59]. This is particularly true for bacteria, where genes from the same pathway are often organized in operons, but it was recently shown to be applicable in eukaryotes as well [60]. Except for linear proximity, the same holds for genes that are close in three-dimensional space, as these tend to be co-regulated [61] (Figure 4).…”