Related Experiment Video
Updated: Mar 8, 2026
09:31
Expression of Fluorescent Proteins in Branchiostoma lanceolatum by mRNA Injection into Unfertilized Oocytes
Published on: January 12, 2015
11.5K
Subfunctionalization of COX4 paralogs in fish
Danielle Porplycia1, Gigi Y Lau2, Jared McDonald1
1Department of Biology, Queen's University, Kingston, Ontario, Canada; and.
Summary
Cytochrome c oxidase subunit 4-2 (COX4-2) in tilapia shows unique regulation and partitioning, differing from mammals. This fish COX4-2 exhibits distinct kinetic properties and cellular localization, indicating subfunctionalization.
Area of Science:
- Mitochondrial respiration
- Comparative genomics
- Biochemistry
Background:
- Cytochrome c oxidase (COX) subunit 4 has two paralogs, COX4-1 and COX4-2, in vertebrates.
- Mammalian COX4-2 is hypoxia-responsive with altered kinetics, but its function in other vertebrates is unclear.
- Phylogenetic analysis indicates COX4-2 diverged more rapidly than COX4-1.
Purpose of the Study:
- To investigate the structure-function and regulation of COX4-2 orthologs in fish (tilapia).
- To compare COX4-2 regulation and function in fish with that of mammals.
- To explore the subfunctionalization of COX4 paralogs in non-mammalian vertebrates.
Main Methods:
- Phylogenetic analysis of COX4 paralogs.
- Measurement of COX4-1 and COX4-2 mRNA and protein levels in tilapia tissues under normoxia and hypoxia.
- Enzyme kinetic assays of COX activity with varying ATP and oxygen concentrations.
- Cellular and subcellular localization studies of COX4 paralogs in tilapia heart.
Main Results:
- Tilapia COX4-1 and COX4-2 protein levels mirrored mRNA levels and were not affected by hypoxia.
- A size-dependent shift from COX4-1 to COX4-2 was observed in tilapia heart and brain.
- ATP allosterically inhibited COX velocity and oxygen affinity in both muscle (COX4-2 predominant) and gill (COX4-1 predominant).
- COX4 paralogs showed cellular and subcellular segregation in tilapia heart mitochondria, with subsarcolemmal mitochondria enriched in COX4-1 and intermyofibrillar mitochondria in COX4-2.
Conclusions:
- Fish COX4-2 exhibits unique transcriptional and post-translational regulation compared to mammals.
- COX4-2 in fish demonstrates subfunctionalization, with distinct kinetic properties and tissue/subcellular localization.
- These findings highlight the divergent evolutionary paths and functional specialization of COX4 paralogs across vertebrate lineages.
Related Concept Videos
02:37Gene Duplication and Divergence
8.1K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
8.1K
02:32Osmoregulation in Fishes
54.2K
When cells are placed in a hypotonic (low-salt) fluid, they can swell and burst. Meanwhile, cells in a hypertonic solution—with a higher salt concentration—can shrivel and die. How do fish cells avoid these gruesome fates in hypotonic freshwater or hypertonic seawater environments?
54.2K
02:02Cis-regulatory Sequences
12.1K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
12.1K
01:57Gene Families
10.1K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
10.1K
01:33Pleiotropy
43.7K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.7K