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Mitochondrial Competition Can Defy Natural Selection With Selfish Drive

Mitochondrial, Mitochondrial Competitio

 

May the best man win. Darwin’s principle of natural selection dictates that organisms with advantageous adaptations will trump those of lesser stock.

The unusual inheritance pattern of mitochondrial DNA, however, sometimes defies the confines of this theory; in a study published June 2016  in Nature Genetics, by Hansong Ma and Patrick H O’Farrel, it was revealed that mitochondrial DNA with detrimental mutations can occasionally outcompete healthier units due to a distorting selfish drive.

The force of ‘selfish selection’ may favor undesirable traits and skew the competition between rival genomes which vie for evolutionary spotlight. Since the competitive ability of donor mitochondrial genomes is a critical factor in the treatment of mitochondrial disorders, researchers are eager to uncover the parameters of a selfish drive’s manipulative influence [1].

Mitochondrial Boxing Ring

While nuclear genes, the standard chromosomes of classical genetics, represent an assorted mixture of both maternal and paternal DNA, mitochondrial genes are inherited from the maternal side alone. As such, mitochondrial DNA (mtDNA) typically does not have to face any hereditary competitors and can safely assume its place in the next organismal generation. Mitochondrial lineage, however, branches across countless species with distinct biological characteristics. Not all mitochondria are created equal [2]. Forcing different mitochondrial genomes into one environment results in inter-organelle competition- but the victor is sometimes unexpected [1].

Working with fly populations, the researchers transplanted mitochondria-filled cytoplasm from one specimen to another to create heteroplasmy – simultaneous presence of different mtDNAs. They found that when closely related mtDNA competed, purifying selection prevailed and the healthiest genome eventually dominated inheritance. Among distantly related mtDNA, though, selfish selection could promote even mutated mtDNAs.

For instance, scientists engineered Drosophila melanogaster flies with temperature-sensitive mutant mtDNAs, lacking the functional mtCol genes required for oxidative phosphorylation. An undamaged relative mtDNA easily triumphed over its substandard cousin; after rounds of breeding, transmission of the mutant declined and the healthy mtDNA was inherited alone. Yet when the mutant was mixed with the distantly related ATP6 genome, the mutant slowly choked ATP6 out of the picture. Initially, both were transmitted in tandem and ATP6 provided the missing function at the restrictive temperature. As ATP6 dwindled due to competitive pressure, the flies died because their remaining mutant mtDNAs couldn’t withstand the heat. The tainted genome had demonstrated the capacity to selfishly assert itself despite its deleterious nature. [1].

As ATP6 dwindled due to competitive pressure, the flies died because their remaining mutant mtDNAs couldn’t withstand the heat. The tainted genome had demonstrated the capacity to selfishly assert itself despite its deleterious nature. [1].

Competition Control Panel

Over time, select emerging population lines ‘cheated’ the system by exhibiting recombinant mtDNAs, consisting of ATP6’s entire coding genome and the temperature-sensitive mutant’s entire noncoding genome. The recombinant’s prevalence increased overtime, indicating its snowballing ability to overthrow the mutant’s destructive reign. It therefore, seemed that the mtDNA’s noncoding region dictated its competitive strength [1].

But mtDNA’s noncoding segment is a variable string of nucleotides. From one organism to another, its composition may differ significantly in length and chemical makeup. To gain a more comprehensive understanding of how the noncoding region accounts for competitive ability and selfish selection, the researchers combined mtDNA from the Drosophila yakuba fly with the temperature-sensitive mutant mtDNA from Drosophila melanogaster. The flies shared a genus rather than a direct species, and D. yakuba’s mtDNA was noticeably shorter and diverged. How would this inter-species mitochondrial competition compare to the first experimental case which involved only D. melanogaster [1]?

More of the Same

At 25 degrees Celsius, a non-restrictive temperature, D. yakuba’s mtDNA became virtually nonexistent. Contrary to the very underpinnings of the theory of natural selection, selfish selection continued to support transmission of the functionally compromised mutant. Once the thermostat edged into restrictive territory, purifying selection could finally kick in and allow for a low level of D. yakuba mtDNA throughout the subsequent generations since the mutant was physically incapable of ensuring the populations’ survivals. When mutant D. melanogaster mtDNA was extinguished by a targeted restriction enzyme, D. yakuba mtDNA claimed control of the driving seat- proving that it had had the ability to do so all along. It had simply been forced into submission by the selfish power which propelled the incompetent mutant [1].

Implication

Although selfish drive is a conniving force, its exact mechanism is unknown. Since it has been traced to mtDNA’s noncoding region, the area containing mtDNA’s origin of replication, some suggest that the ability to selfishly compete is linked to replicative strength.

Nevertheless, many factors remain unclear. The competitive hierarchy is unpredictable, as a weak mtDNA genome may win one battle yet forfeit another of equivalent difficulty. Even the native genome does not have any home-advantage; it is equally subject to potential failure. Now that the topic surface has been breached, researchers will continue to analyze the phenomenon of selfish drive and gather data which may advance treatment of mitochondrial disorders [1].

Sources:

[1] http://www.nature.com/ng/journal/v48/n7/full/ng.3587.html
[2] https://www.bradshawfoundation.com/journey/eve.html

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    By: Avigail Goldberger

    Avigail Goldberger is an avid science devotee, with a particular interest in biology, genetics, and neuroscience. Her love of STEM subjects is equally matched by a passion for literature and writing, so she hopes that her eventual profession will synthesize her multifaceted academic drives.

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