Genome Evolutionary Dynamics Meets Functional Genomics: A Case Story on the Identification of SLC25A44.

Behrooz Darbani

doi:10.3390/ijms22115669

Abstract

Gene clusters are becoming promising tools for gene identification. The study reveals the purposive genomic distribution of genes toward higher inheritance rates of intact metabolic pathways/phenotypes and, thereby, higher fitness. The co-localization of co-expressed, co-interacting, and functionally related genes was found as genome-wide trends in humans, mouse, golden eagle, rice fish, Drosophila, peanut, and Arabidopsis. As anticipated, the analyses verified the co-segregation of co-localized events. A negative correlation was notable between the likelihood of co-localization events and the inter-loci distances. The evolution of genomic blocks was also found convergent and uniform along the chromosomal arms. Calling a genomic block responsible for adjacent metabolic reactions is therefore recommended for identification of candidate genes and interpretation of cellular functions. As a case story, a function in the metabolism of energy and secondary metabolites was proposed for Slc25A44, based on its genomic local information. Slc25A44 was further characterized as an essential housekeeping gene which has been under evolutionary purifying pressure and belongs to the phylogenetic ETC-clade of SLC25s. Pathway enrichment mapped the Slc25A44s to the energy metabolism. The expression of peanut and human Slc25A44s in oocytes and Saccharomyces cerevisiae strains confirmed the transport of common precursors for secondary metabolites and ubiquinone. These results suggest that SLC25A44 is a mitochondrion-ER-nucleus zone transporter with biotechnological applications. Finally, a conserved three-amino acid signature on the cytosolic face of transport cavity was found important for rational engineering of SLC25s.

Highlights

Published: 26 May 2021Knockout, RNAi, and overexpression libraries, classical genetics, transcriptomics, and proteomics are the mostly used, and very laborious, approaches to inferring the functions of genes
The analyses found the flavonoid and stilbenoid biosynthetic pathway genes and the genes coding for subunits of mitochondrial electron transfer chains (ETC), such as ubiquinone oxidoreductases co-localized with Slc25A44
We have previously used the information of biosynthetic gene clusters for identification of membrane transporters [2,3]

Summary

Introduction

Published: 26 May 2021Knockout, RNAi, and overexpression libraries, classical genetics, transcriptomics, and proteomics are the mostly used, and very laborious, approaches to inferring the functions of genes. This study generalizes the approach by revealing sharp genome-wide co-localization patterns for co-expressed and co-interacting genes in plant and animal genomes. It highlights the genomic co-localization of functionally related genes in several species. Co-localization of genes which are responsible for different steps of a metabolic pathway, leads to a higher frequency of the intact pathway among the offspring. This is due to the co-segregation of the co-localized active alleles to the generations. Individuals with co-localized genes responsible for a decisive phenotype in the struggle for life, outcompete those with the randomly distributed responsible genes

Methods

Results

Conclusion