Same Gene, Different Functions

Proteins encoded by the same gene can play very different roles in the cell, scientists show.

By Catherine Offord | February 12, 2016

CD46, a type I membrane protein, has at least 14 different isoforms.WIKIMEDIA, EMWThe human genome contains roughly 20,000 protein-coding genes, yet the number of proteins in human cells is thought to be more like 100,000. Researchers from three institutions in North America have now shown that at least some of the diversity of proteins’ functions in the cell may be due to the widely diverging roles of protein isoforms—structurally similar variants produced as a result of slight differences during the translation of a single gene. The findings were published yesterday (February 11) in Cell.

“The exciting discovery was that isoforms coming from the same gene often interacted with different protein partners,” study coauthor Gloria Sheynkman of the Dana-Farber Cancer Institute said in a statement. “This suggests that the isoforms play very different roles within the cell.”

Unlike previous functional studies of isoforms, which have generally focused on one or a handful of genes, this project systematically analyzed the interactions of multiple isoforms from hundreds of genes.

The researchers found that, on average, two related isoforms shared less than 50 percent of interacting proteins; 16 percent of related isoforms shared none at all. These differences in interaction partners were often associated with only tiny alterations in DNA sequence—sometimes just a single base pair.

“From the perspective of all the protein interactions within a cell, related isoforms behave more like distinct proteins than minor variants of one another,” study coauthor Tong Hao of Dana-Farber said in the statement.

“A more detailed view at protein interaction networks, as presented in our paper, is especially important in relation to human diseases,” added study coauthor Lilia Iakoucheva of the University of California, San Diego. “Drastic differences in interaction partners among splicing isoforms strongly suggest that identification of the disease-relevant pathways at the gene level is not sufficient. . . . It’s time to take a deeper dive into the networks that we are building and analyzing.”

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Avatar of: James V. Kohl

James V. Kohl

Posts: 525

February 12, 2016

These differences in interaction partners were often associated with only tiny alterations in DNA sequence—sometimes just a single base pair.

UV light induced energy-dependent hydrogen-atom transfer in DNA base pairs in soluiton links the nutrient-dependent micrroRNA/messsenger RNA balance from alternative splicings to RNA-mediated amino acid substitutions and DNA repair, which links supercoiled DNA in all living genera to the physiology of reproduction and protection from virus-driven entropy.

All experimental evidence of biologically-based cause and effect links nutrient-dependent biophysically constrained RNA-mediated protein folding chemistry from alternative RNA splicings to all biodiversity via thermodynamic cycles of protein biosynthesis and degradation.

Virus-driven energy theft perturb the cycles. That is how viruses are linked to all pathology.

Neo-Darwinian theorists still seem to be horribly confused about the difference between an amino acid substitution and a mutation. They claim that energy theft by viruses links mutations to evolution. 

What are you teaching your students about how the microRNA/messenger RNA balance is linked to RNA-mediated cell type differentiation?

Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Random mutations that somehow cause one or more amino acid substitutions are not likely to simultaneously cause adaptive evolution from the bottom up via the thermodynamics of chromatin remodeling and control of adaptive evolution from the top down via organism-level thermoregulation. However the nutrient-dependent substitution of alanine for valine (Grossman et al., 2013; Kamberov et al., 2013) appears to result in species-specific organism-level changes in skin, glands, and hair, through pheromone-controlled reproduction.

Avatar of: James V. Kohl

James V. Kohl

Posts: 525

Replied to a comment from James V. Kohl made on February 12, 2016

February 12, 2016

See also: Alternative RNA Splicing in Evolution

...alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.

with my comments on publication of our 1996 Hormones and Behavior review From Fertilization to Adult Sexual Behavior

In our section on molecular epigenetics we wrote:

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.


Avatar of: James V. Kohl

James V. Kohl

Posts: 525

February 13, 2016

See also: Watching sensory information translate into behavior

See also: Scientists identify the brain circuits with which newly hatched nematodes form and retrieve a lifelong aversive olfactory memory.

Energy-dependent hydrogen-atom transfer in DNA base pairs in solution links UV light to information transfer during life history transitions. The transitions link odors and pheromones from feedback loops to metabolic networks and genetic networks in species from microbes to humans. RNA-mediated amino acid substitutions must be included in the context of explanations based on what is currently known to serious scientists about cell type differentiation and supercoiled DNA.

What is known will come as no surprise to anyone who has followed the extant literature across disciplines for the past two decades. For example, some of it is being presented tomorrow at the AAAS 2016 annual meeting in this symposium.

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