This week in Molecular Biology and Evolution: A step ahead of influenza, honeybee sex

Every fall, the latest batch of flu vaccines attempts to keep society a step ahead of the evolution of the flu virus. Heroic worldwide surveillance efforts have avoided a repeat of the 1918 flu pandemic, but as shown in the recent H1N1 outbreak, viruses can still outwit even the best public health efforts.

During the H1N1 outbreak, antiviral drugs offered the only hope against emergent flu strains. Two drug classes: adamantanes (FDA approved in 1966) and neuraminidase inhibitors (oseltamivir, FDA approved in 1999) represent two classes of drugs that target viral an ion channel and a cell surface antigen, respectively, hereby preventing or treating infection.

In an ambitious study, the authors attempt to trace drug resistance against all strains of the flu by using an extensive influenza virus database containing all known genetic sequence information (70,000 complete nucleotide sequences) for influenza strains. Using a phylogenetic approach, authors Vanessa Garcia and Stéphane Aris-Brosou examined the evolutionary history of antiviral drug resistance. "Although the approaches employed in our study are not novel in themselves, the scale of the analyses is unprecedented and allowed us to track in public databases the dynamics of all known mutations involved in drug resistance", reported the senior author.

How does the virus outwit two leading antiviral therapies? Widespread use of these drugs has led to the emergence of drug resistance. Most disconcerting, recent "dual resistance" viruses dodge both drugs, leaving us defenseless against the virus. While adamantane resistance mutations appeared readily, it took 15-38 years after FDA approval to emerge, but emerged 3 times, whereas, the less spontaneous oseltamivir mutations took at most 7 years, serving as a public health cautionary tail. The authors support the judicious use of antiviral drugs as a last line of defense against influenza to avoid the spread of dual resistance, which is already circulating in H1N1 viruses in humans. "Our results also suggest that most of the mutations leading to influenza drug resistance are on the wane, so that recent efforts in controlling drug use are paying off, but we should remain vigilant," commented Stéphane Aris-Brosou.

There is an exquisite genetic control behind a honeybee's fate in the hive---from the lowly drone to the almighty queen---which literally, represents the bees knees for evolutionary scientists exploring how multiple mutations, or alleles, of a single gene called the complementary sex determiner (csd) can have a profound influence on honeybee society.

Unlike people, there are no X and Y sex chromosomes for bees. Rather, sex is determined by a single gene csd and its allelic composition and whether or not a queen bee choses to fertilize her eggs. Female bees (queens or workers) come from fertilized eggs, receiving always two different (heterozygote) copies of csd. Fertile males always come from unfertilized eggs, receiving only one copy of csd. Two identical (homozygote) copies of csd in fertilized eggs is always lethal; these individuals are being killed at the early larval stage by worker bees as they would develop into diploid males which do not contribute to colony fitness.

Lechner, et al., have now examined the exquisite molecular control behind the sex determination, finely identifying and tracing back a comprehensive number of csd alleles to create a richer understanding of the variability of the csd gene over evolutionary time. They looked at a data set of 244 csd sequences from queens, worker bees and drones, and showed that the total number of csd alleles found in bees ranges from at least 53 (locally) to 87 (worldwide), which is much higher than previously reported (20). Using an evolutionary model, they also extrapolated the presence of total 116-145 csd alleles worldwide, a great example of the enormous sequence variability within csd. They were able to finely decipher the minimum number of mutations leading to heterozygous csd, identify faster evolving hot spots within the csd gene, and how these may contribute to variability.

"Comprehensive insights into the sequence variability of the sex determining gene csd in honeybees elucidate the evolutionary processes that lead to the enormous number of csd-alleles found worldwide," said Hasselmann

Finally, they traced the data back over evolutionary time and found that a novel csd function affecting sex determination arises about every 400,000 years. The study provides one of the most comprehensive views of the enormous genetic diversity and the evolutionary forces shaping sex determination in bees, as well as how changes in csd affect honey bee colony fitness.