Daily Archives: December 18, 2014

PUBLIC RELEASE DATE:

18-Dec-2014

Contact: Mary Clarke press.office@sanger.ac.uk 44-122-349-2368 Wellcome Trust Sanger Institute @sangerinstitute

A study of the way malaria parasites behave when they live in human red blood cells has revealed that they can rapidly change the proteins on the surface of their host cells during the course of a single infection in order to hide from the immune system.

The findings, which overturn previous thinking about the Plasmodium falciparum parasite's lifecycle, could explain why so many attempts to create an effective vaccine have failed and how the parasites are able to survive in the human body for such long periods of time.

In the study, Plasmodium falciparum parasites were kept dividing in human blood for over a year in the laboratory, with the full parasite genome being sequenced regularly. This gave the scientists snapshots of the parasite's genome at multiple time points, allowing them to track evolution as it unfolded in the lab. They found that the 60 or so genes that control proteins on the surface of infected human blood cells, known as var genes, swapped genetic information regularly, creating around a million new and unrecognisable surface proteins in every infected human every two days.

"These genes are like decks of cards constantly being shuffled," explains William Hamilton, a first author from the Wellcome Trust Sanger Institute. "The use of whole genome sequencing and the sheer number of samples we collected gave us a detailed picture of how the var gene repertoire changes continuously within red blood cells."

The results show, for the first time, that the process of swapping genetic information, known as recombination, happens not when the malaria parasite is inside the mosquito, as previously thought, but during the asexual stage of the parasite's lifecycle inside human blood cells. This may go some way to explaining how chronic asymptomatic infection, a crucial problem for malaria elimination, is possible.

"It's very likely that mosquitos are re-infected with Plasmodium falciparum parasites at the beginning of each wet season by biting humans who have carried the parasites, often asymptomatically, for up to eight months during the dry season," says Dr Antoine Claessens, a first author from the Malaria Programme at the Wellcome Trust Sanger Institute. "During those months the parasite's var genes are busy recombining to create millions of different versions - cunning disguises that mean they remain safe from the immune system and ready for the new malarial season."

While further work will be required to fully understand the mechanism driving the recombination of Plasmodium falciparum's var genes, scientists were able to calculate the rate at which it happens. They found that var gene recombination takes place in about 0.2 per cent of parasites after each 48-hour life cycle in the red blood cell. With about a billion parasites living inside a typical infected human, there is huge potential for the parasite to create new, recombined var genes inside each person with malaria. This pace of change far exceeds that of genes in any other region of the parasite's genome.

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Fast-changing genes help malaria to hide in the human body

PUBLIC RELEASE DATE:

18-Dec-2014

Contact: Shozo Yokoyama syokoya@emory.edu PLOS

The evolution of trichromatic color vision in humans occurred by first switching from the ability to detect UV light to blue light (between 80-30 MYA) and then by adding green-sensitivity (between 45-30 MYA) to the preexisting red-sensitivity in the vertebrate ancestor. The detailed molecular and functional changes of the human color vision have been revealed by Shozo Yokoyama et al. Emory University and is published in the journal PLOS Genetics.

The molecular basis of functional differentiation is a fundamental question in biology. To fully appreciate how these changes are generated, it is necessary to evaluate the relationship between genes and functions. This is a difficult task because new mutations can produce different functional changes when they occur with different preexisting mutations, causing complex non-additive interactions.

The blue-sensitive visual pigment in human evolved from the UV-sensitive pigment in the ancient Boreoeutherian ancestor by seven mutations. There are 5,040 possible evolutionary paths connecting them. The team examined experimentally the genetic composition and color perception of the visual pigment at every evolutionary step of all 5,040 trajectories. They found that 4,008 trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Eight most likely trajectories reveal that the blue-sensitivity evolved gradually almost exclusively by non-additive interactions among the seven mutations.

These analyses demonstrates that the historical sequence of change is critical to our understanding of molecular evolution and emphasizes that genetic engineering of ancestral molecules is the key to decode the complex interactions of mutations within a protein and their effects on functional change.

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The fine-tuning of human color perception