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What Makes One Strain of the Exceptional Neurospora Fungus So Exceptional

What Makes One Strain of the Exceptional Neurospora Fungus So Exceptional

Neurospora crassa. Image:

Mutations are widely considered to be detrimental to an organism because they alter the genome in unpredictable ways. So it might come as a surprise that the Neurospora fungus maintains genes that increase the occurrence of mutations.

Neurospora has the highest known mutation rate among all life forms. This rate is 100- to 1,000-fold higher than in humans, rice and fruit flies, and 10,000-fold higher than in the bacterium Escherichia coli. Only RNA viruses have a higher mutation rate.

Scientists determined Neurospora‘s mutation rate by mating two Neurospora individuals – two strains – with each other, and sequenced their genomes as well as the genomes of all four of their progeny. (The results were published in a paper last year.) They determined that two genes, called rid and dim-2, were implicated in the high mutation rate, since the rate was a 100-fold lower in a mating between strains that lacked these genes.

These genes are involved in a process called repeat-induced point mutation (RIP) that occurs only during mating. RIP searches the genome for the presence of any gene-sized stretch of DNA sequence present more than once (i.e. more than once), and then riddles all the copies with multiple mutations. This irretrievably destroys the integrity of any gene present in more than one copy.

Thanks to RIP, the Neurospora genome does not contain any duplicated genes and transposons. Transposons, also known as ‘jumping genes’, are DNA sequences that can change their position within a genome, and do so by duplicating themselves and increasing their number. All other genomes, including ours, contain many duplicated genes and transposons – but the Neurospora genome is an exception.

Incredibly, one exceptional Neurospora strain collected from Adiopodoumé, in Côte d’Ivoire, was found to contain copies of a transposon called Tad. All the hundreds of other Neurospora strains examined, including some obtained in subsequent collections from Adiopodoumé, contained only relics of Tad that had accumulated RIP mutations and, consequently, lost the ability to jump.

How can we account for the Tad transposon’s survival in just this one strain?

This question is of importance to biologists because it seeks to understand the origin of an outlier individual in a species that itself is an outlier relative to all other species. Moreover, targeted alteration of duplicated DNA in Neurospora bears some resemblance to how we generate antibody diversity in our own bodies.

A 2011 study by scientists at the Centre for Cellular and Molecular Biology, Hyderabad, could have the answer. (I was one of the coauthors.)

The scientists engineered a Neurospora strain to carry an extra copy of a segment of a gene required to synthesise a compound called sterol. When this strain was mated with another, the duplicated segment caused RIP mutations to be induced in the sterol synthesis gene. This produced mutant progeny unable to make sterol. The mutant colonies had a distinctly different appearance than colonies from their non-mutant siblings. This made it easy to distinguish between the two types – and scientists could conveniently score the efficiency of RIP in the mating.

Felicite Noubissi, a PhD student, mated the engineered strain with 446 Neurospora strains collected from around the world. Most matings yielded 2% to 20% mutant progeny, but the matings with seven strains yielded less than 0.05%, indicating that they suppressed RIP. The Adiopodoumé strain was one of the seven. Although the other six suppressors did not contain Tad elements, they may contain extra copies of other DNA sequences.

Another PhD student, Parmit Singh, asked whether the frequency of sterol mutant progeny would be affected if a second, longer stretch of duplicated DNA was present in either parental strain during mating. A strain bearing more than one copy of a long DNA stretch, referred to as ‘Dp’, can be obtained by crossing normal sequence strains and ones in which a chromosome rearrangement transfers a segment of one chromosome into another.

For example, consider a rearrangement that transfers a 100-gene stretch from chromosome 1 to chromosome 2. Each progeny inherits one or the other copy of each pair of parental chromosomes. Progeny that inherit chromosome 1 from the normal parent and chromosome 2 from the translocation parent are called ‘Dp type’.

Singh mated the engineered strain with more than 40 different Dp strains and found that most of them suppressed RIP, and sterol mutant progeny were not generated. Presumably, the large duplication soaked up the RIP machinery, and none was available at the sterol synthesis gene’s duplicated segment. But five Dp strains did not.

The suppressor and non-suppressor Dp strains had different sizes. In the suppressor Dp strains, the duplicated segment was as long as 39 or more Tad elements, whereas in the non-suppressor it was 29 or less.

The number of Tad elements in the Adiopodoumé strain is yet to be determined. And it can be ascertained by sequencing its genome. If the Adiopodoumé strain has 39 or more, it should be able to suppress RIP. Most Neurospora strains likely accumulated only a sub-threshold number, and if they didn’t have any other DNA sequence in more than one copy, they stood to lose all their Tad elements to disruption by RIP.

Accumulating a large trousseau of Tad elements might not be easy. It might have happened infrequently, possibly just once, in Adiopodoumé. That numerous Tad elements can together impart RIP suppression, which, in turn, allows evasion from RIP, has a nice touch of yin and yang interdependence.

D.P. Kasbekar is a retired scientist.

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