Discovery Of Novel Genes Could Unlock Mystery Of What Makes Us Uniquely Human

Humans and chimpanzees are genetically very similar, yet it is not difficult to identify the many ways in which we are clearly distinct from chimps. In a study published online in Genome Research, scientists have made a crucial discovery of genes that have evolved in humans after branching off from other primates, opening new possibilities for understanding what makes us uniquely human.The prevailing wisdom in the field of molecular evolution was that new genes could only evolve from duplicated or rearranged versions of preexisting genes. It seemed highly unlikely that evolutionary processes could produce a functional protein-coding gene from what was once inactive DNA.

However, recent evidence suggests that this phenomenon does in fact occur. Researchers have found genes that arose from non-coding DNA in flies, yeast, and primates. No such genes had been found to be unique to humans until now, and the discovery raises fascinating questions about how these genes might make us different from other primates.

In this work, David Knowles and Aoife McLysaght of the Smurfit Institute of Genetics at Trinity College Dublin undertook the painstaking task of finding protein-coding genes in the human genome that are absent from the chimp genome. Once they had performed a rigorous search and systematically ruled out false results, their list of candidate genes was trimmed down to just three. Then came the next challenge. "We needed to demonstrate that the DNA in human is really active as a gene," said McLysaght.

The authors gathered evidence from other studies that these three genes are actively transcribed and translated into proteins, but furthermore, they needed to show that the corresponding DNA sequences in other primates are inactive. They found that these DNA sequences in several species of apes and monkeys contained differences that would likely disable a protein-coding gene, suggesting that these genes were inactive in the ancestral primate.

The authors also note that because of the strict set of filters employed, only about 20% of human genes were amenable to analysis. Therefore they estimate there may be approximately 18 human-specific genes that have arisen from non-coding DNA during human evolution.

This discovery of novel protein-coding genes in humans is a significant finding, but raises a bigger question: What are the proteins encoded by these genes doing? "They are unlike any other human genes and have the potential to have a profound impact," McLysaght noted. While these genes have not been characterized yet and their functions remain unknown, McLysaght added that it is tempting to speculate that human-specific genes are important for human-specific traits.

Scientists from the Smurfit Institute of Genetics, Trinity College Dublin (Dublin, Ireland) contributed to this study.

This work was supported by a President of Ireland Young Researcher Award from Science Foundation Ireland.

New iPhone App 'Outbreaks Near Me' Locates H1N1 (Swine Flu), Infectious Diseases

A new iPhone application, created by researchers at Children's Hospital Boston in collaboration with the MIT Media Lab, enables users to track and report outbreaks of infectious diseases, such as H1N1 (swine flu), on the ground in real time.The application, "Outbreaks Near Me," builds upon the mission and proven capability of HealthMap, an online resource that collects, filters, maps and disseminates information about emerging infectious diseases, and provides a new, contextualized view of a user's specific location – pinpointing outbreaks that have been reported in the vicinity of the user and offering the opportunity to search for additional outbreak information by location or disease.

Additional functionality of Outbreaks Near Me is the ability to set alerts that will notify a user on their device or by e-mail when new outbreaks are reported in their proximity, or if a user enters a new area of activity.

"We hope individuals will find the new app to be a useful source of outbreak information – locally, nationally, and globally," says HealthMap co-founder John Brownstein, PhD, assistant professor in the Children's Hospital Informatics Program (CHIP). "As people are equipped with more knowledge and awareness of infectious disease, the hope is that they will become more involved and proactive about public health."

The new application also features an option for users to submit an outbreak report. This will enable individuals in cities and countries around the world to interact with the HealthMap team and participate in the public health surveillance process. Users may take photos – of situations and scenarios of, and/or leading to, disease – with their iPhone and submit them to the HealthMap system for review and eventual posting as an alert on the worldwide map.

"This is grassroots, participatory epidemiology," says HealthMap co-founder Clark Freifeld, a PhD student at the MIT Media Lab and research software developer at CHIP. "In releasing this app we aim to empower citizens in the cause of public health, not only by providing ready access to real-time information, but also by encouraging them to contribute their own knowledge, expertise, and observations. In enabling participation in surveillance, we also expect to increase global coverage and identify outbreaks earlier."

HealthMap was founded in 2006 and mines the Internet – searching disparate data sources such as news reports, curated personal accounts, official alerts, blogs and chat rooms – to track and map infectious disease outbreaks. While the data have been shown to provide early information on new outbreaks, users are encouraged to interpret the data appropriately as it is drawn from both official and unofficial sources.

The HealthMap Web site (http://www.healthmap.org) averages 10,000 unique visits a day, including regular users from the World Health Organization, the CDC, and the European Centre for Disease Prevention and Control. During the peak of H1N1 swine flu this spring, visits to the site rose substantially, with as many as 150,000 visitors coming to the Web site to search for information.

Outbreaks Near Me was developed with support from Google.org and is available at no cost for download in the iTunes App Store. For more information on Outbreaks Near Me, visit: http://healthmap.org/iphone.php.

We Are All Mutants: Measurement Of Mutation Rate In Humans By Direct Sequencing

An international team of 16 scientists today reports the first direct measurement of the general rate of genetic mutation at individual DNA letters in humans. The team sequenced the same piece of DNA - 10,000,000 or so letters or 'nucleotides' from the Y chromosome - from two men separated by 13 generations, and counted the number of differences. Among all these nucleotides, they found only four mutations.In 1935 one of the founders of modern genetics, J. B. S. Haldane, studied men in London with the blood disease haemophilia and estimated that there would be one in 50,000 incidence of mutations causing haemophilia in the gene affected - the equivalent of a mutation rate of perhaps one in 25 million nucleotides across the genome. Others have measured rates at a few further specific genes or compared DNA from humans and chimpanzees to produce general estimates of the mutation rate expressed more directly in nucleotides of DNA.

Remarkably, the new research, recently published in Current Biology, shows that these early estimates were spot on - in total, we all carry 100-200 new mutations in our DNA. This is equivalent to one mutation in each 15 to 30 million nucleotides. Fortunately, most of these are harmless and have no apparent effect on our health or appearance.

"The amount of data we generated would have been unimaginable just a few years ago," says Dr Yali Xue from the Wellcome Trust Sanger Institute and one of the project's leaders. "But finding this tiny number of mutations was more difficult than finding an ant's egg in the emperor's rice store."

Team member Qiuju Wang recruited a family from China who had lived in the same village for centuries. The team studied two distant male-line relatives - separated by thirteen generations - whose common ancestor lived two hundred years ago.

To establish the rate of mutation, the team examined an area of the Y chromosome. The Y chromosome is unique in that, apart from rare mutations, it is passed unchanged from father to son; so mutations accumulate slowly over the generations.

Despite many generations of separation, researchers found only 12 differences among all the DNA letters examined. The two Y chromosomes were still identical at 10,149,073 of the 10,149,085 letters examined. Of the 12 differences, eight had arisen in the cell lines used for the work. Only four were true mutations that had occurred naturally through the generations.

We have known for a long time that mutations occur occasionally in each of us, but have had to guess exactly how often. Now, thanks to advances in the technology for reading DNA, this new research has been possible.

Understanding mutation rates is key to many aspects of human evolution and medical research: mutation is the ultimate source of all our genetic variation and provides a molecular clock for measuring evolutionary timescales. Mutations can also lead directly to diseases like cancer. With better measurements of mutation rates, we could improve the calibration of the evolutionary clock, or test ways to reduce mutations, for example.

Even with the latest DNA sequencing technology, the researchers had to design a special strategy to search for the vanishingly rare mutations. They used next-generation sequencing to establish the order of letters on the two Y chromosomes and then compared these to the Y chromosome reference sequence.

Having identified 23 candidate SNPs - or single letter changes in the DNA - they amplified the regions containing these candidates and checked the sequences using the standard Sanger method. A total of four naturally occurring mutations were confirmed. Knowing this number of mutations, the length of the area that they had searched and the number of generations separating the individuals, the team were able to calculate the rate of mutation.

"These four mutations gave us the exact mutation rate - one in 30 million nucleotides each generation - that we had expected," says the study's coordinator, Chris Tyler-Smith, also from The Wellcome Trust Sanger Institute. "This was reassuring because the methods we used - harnessing next-generation sequencing technology - had not previously been tested for this kind of research. New mutations are responsible for an array of genetic diseases. The ability to reliably measure rates of DNA mutation means we can begin to ask how mutation rates vary between different regions of the genome and perhaps also between different individuals."

This work was supported by the Joint Project from the NSFC and The Royal Society, and the Wellcome Trust.