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Do Humans and Fungi Sometimes Retain Genes That Serve No Purpose?

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Neurospora crassa. Image: devbio.biology.gatech.edu

When a normal strain, called N, of the fungus Neurospora is mated with a strain in which an extra copy of any gene is inserted anywhere in the genome, something unexpected happens. The extra copy is detected as unpaired – since it does not have a partner from the N parent. For all other genes, the maternal and paternal chromosomes carry a copy apiece, and hence they are seen as paired.

Small RNA molecules are made whose sequence matches that of the unpaired gene’s DNA, and are incorporated into a gene silencing complex. The complex then silences all genes with a matching sequence. Such gene silencing, called ‘meiotic silencing by unpaired DNA’ (MSUD), effectively shuts down one or several singleton genes, as though they were gatecrashers at a couples-only party. Although the native, or endogenous, gene copies are paired, they are silenced as well, since they share DNA sequence with the extra copy. In sum, any gene whose DNA matches the small RNA is silenced.

Ascospores are the ‘babies’ from a Neurospora mating, and their germination releases the progeny mycelium. Normally, ascospores are ellipsoidal in shape. But if a gene called r (for “round ascospores”) is mutated or silenced, then they become round.

Consider a strain with an extra copy of the r gene – called r-ex. In the mating of an r-ex and an N, a normal strain, all copies of the r gene are silenced. Thus, no r product is made. And the fraction of round ascospores produced gives us an estimate of the MSUD efficiency.

Most Neurospora studies have used strains of the “OR” genetic background of Neurospora crassa. In this background, r-ex and N matings made more than 99% round ascospores, whereas r-ex and r-ex and N and N crosses made fewer than 1%.  The latter had no unpaired genes, so there was no gene silencing.

Scientists (led by this author) at the Centre for DNA Fingerprinting and Diagnostics, Hyderabad, discovered that r-ex and N matings in a different N. crassa background called BS, or in strain 85 of the related species N. tetrasperma, produced fewer than 60% and 10% round ascospores. This showed that MSUD efficiency differs widely in different backgrounds.

About 50 years ago, the Round spore-1 (Rsp-1) mutant was isolated in the N. tetrasperma strain T-220. All ascospores from Rsp-1 x N crosses were round. Unfortunately the mutant is now lost.

Although impossible to establish now, it is predicted to have contained a deletion that caused the r gene from the N parent to become unpaired and consequently silenced. This suggested that while the OR and BS strains of N. crassa show efficient and inefficient MSUD, respectively, the difference is mirrored in the T-220 and 85 strains of N. tetrasperma, and hinted to the possibility of a trans-species polymorphism. That is, the presence of gene variants in the two Neurospora species which are more similar to each other than they are to their alternative versions in the same species.

To appreciate why biologists find trans-species polymorphisms interesting, consider a more familiar example. The ABO blood groups were the first genetic polymorphisms discovered in humans. Their discovery led to rational blood transfusion and has saved innumerable lives. Knowledge of the blood groups is now commonplace, and they are even entered in our driving licenses.

An individual has two copies of the ABO gene, one from each parent. Each copy can be one of three versions (also called alleles) – A, B or O. The A allele encodes an enzyme that transfers a sugar called N-acetyl-D-galactosamine to a substrate called H. The B allele encodes one that transfers a different sugar, D-galactose, to the same substrate. The O allele does not encode an enzyme. AA and AO individuals make the A enzyme; BB and BO individuals make the B enzyme, AB individuals make both, and OO make neither. Given that type O individuals are healthy, it follows that these particular enzymes are nonessential for life.

Then why have these blood groups persisted in orangutans, gibbons and macaques as well? No primate species with only type O individuals has yet been found, although chimpanzees have lost the B enzyme, and gorillas the A enzyme.  The A transferases are more similar to each other than they are to the B enzymes. Humans, orangutans, gibbons and macaques last shared a common ancestor about 20 million years ago. What has retained these apparently nonessential enzymes over millions of years in so many species? Has the loss of A or B enzymes from gorillas and chimpanzees been of any consequence?

Neurospora are more experimentally tractable than primates, therefore it is easier to work out the hows and whys of its MSUD diversity. The Neurospora studies might even provide clues to solve the mystery of ABO blood groups.

 

The post Do Humans and Fungi Sometimes Retain Genes That Serve No Purpose? appeared first on The Wire Science.

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