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Genomics In The Journals: Jul 26, 2012

NEW YORK (GenomeWeb News) – A core group of organisms comprise the gut microbiome of chimpanzees, though the animals' broader gut microbial communities are influenced by a range of biological and environmental factors, according to a study by researchers from the US and Tanzania. As they report in the Proceedings of the National Academy of Sciences, the team used 16S ribosomal RNA sequencing to assess gut microbial communities in almost three-dozen chimps from two well-studied chimp communities in Tanzania's Gombe National Park. For the most part, gut microbe profiles clustered with chimp communities, though family ties between animals did not necessarily coincide with more similar gut microbiomes. When the researchers tested seven animals multiple times over nearly a decade — relying on a so-called "iTag" approach for identifying gut microbes from 16S sequences — they found that the chimps' gut microbiomes shared a few features over all of the time points. But features of these microbial communities converged more fully in the final sampling year, study authors noted, coinciding with a rise in excursions by chimps from one group into territory inhabited by the other.

Also in PNAS, a study from researchers at more than a dozen centers around the world looked at polar bear evolution and its relationship to climate. The team sequenced the genomes of five bears to 25 to 100-fold coverage depth: one polar bear, one American black bear, and three brown bears. The latter included two representative from the so-called Admiralty, Baranof, and Chichagof, or ABC, brown bears — brown bears from a group of Alaskan islands that have a closer-than-usual maternal relationship with polar bears. To complement this genome sequence data, researchers sequenced another 22 polar bears to shallower coverage. They also sequenced ancient DNA from a 110,000- to 130,000-year-old polar bear jawbone found in Norway and did transcriptome sequencing on one polar and one brown bear.

Contrary to an intronic sequence analysis published by a German-led group earlier this year, which estimated that polar bears and brown bears diverged from one another some 600,000 years ago, the new genomic analysis pushes that divergence time back even further, suggesting polar bears and brown bears split some 4 million to 5 million years ago. Since then, study authors say, polar bear populations appear to have swelled and waned in ways that seem to correspond to cooler and warmer periods in history. They reasoned that the same climate events could also have contributed to intermittent interbreeding between polar and brown bear populations.

"Maybe we're seeing a hint that in really warm times, polar bears changed their lifestyle and came into contact, and indeed interbred, with brown bears," co-first author Stephan Schuster, a Penn State comparative genomics and bioinformatics researcher who is also affiliated with Singapore's Nanyang Technological University, said in a statement.

A PLoS ONE study describes the proteomics-based approach that an American and Argentinean team used to detect disease in a 500-year-old Andean Incan mummy nicknamed 'The Maiden,' whose remains were among those discovered at high elevation burial sites in 1999. Through mass spectrometry-based shotgun proteomic analyses on a lip swab sample from the mummified girl — who is believed to have died as part of a ritual sacrifice when she was around 15-years-old — the researchers tracked down immune protein profiles resembling those found in modern day samples from individuals with chronic respiratory infections. The results seem to point to an active bacterial lung infection in the Maiden at her time of death. Indeed, 16S rRNA sequence analyses indicate that the girl had one or more potentially pathogenic Mycobacterium species in her upper respiratory tract. On the other hand, proteomic, DNA, and other analyses did not detect signs of such infection in the mummified remains of a seven-year-old boy found at a neighboring burial site.

The forensics proteomics strategy used in the study "opens the door to solving many historical and current biomedical and forensic mysteries, from understanding why the plague of 1918 was so lethal, to finding out which pathogen is responsible for death in cases of multiple infections," according to first author Angelique Corthals, a City University of New York and Stony Brook Medical Center researcher.

"[R]ather than looking for the pathogen, which is notoriously difficult to do in historical samples, we are looking at the immune system protein profile of the 'patient,' which more accurately tells us that there was indeed an infection at the time of death," Corthals said in a statement.

An international team led by investigators at Columbia University has uncovered a cancer-causing gene fusion that characterizes a subset of glioblastoma cases — work that it describes in Science. Using RNA-sequencing combined with a computational method known as TX-Fuse, study authors looked for fusions in temporary cell cultures generated from GBM tumors for nine individuals with the disease. The search led to a suspicious fusion in samples from one patient that involved two genes called FGFR and TACC that are normally found almost 50,000 base pairs apart on chromosome 4. The researchers' subsequent experiments indicate that the FGFR-TACC fusion, found in just over 3 percent of the 97 glioblastoma tumors that they tested, acts as an oncogene in both brain cell lines and mouse models. The protein produced from this fusion gene makes its way to the mitotic spindle poles, they found, where its overactive kinase enzyme activity contributes to mitotic spindle jams during cell division that interfere with accurate chromosome segregation.

"If this process happens incorrectly, you get uneven distribution of the chromosomes," Columbia University pathology and neurology researcher Antonio Iavarone, a co-corresponding author on the study, said in a statement. "This condition, which is known as aneuploidy, is thought to be the hallmark of tumorigenesis."

"From a clinical perspective, we have identified a druggable target for a brain cancer with a particularly dismal outcome," he said. "From a basic research perspective, we have found the first example of a tumor-initiating mutation that directly affects how cells divide, causing chromosomal instability."

Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.

The Scan

Pig Organ Transplants Considered

The Wall Street Journal reports that the US Food and Drug Administration may soon allow clinical trials that involve transplanting pig organs into humans.

'Poo-Bank' Proposal

Harvard Medical School researchers suggest people should bank stool samples when they are young to transplant when they later develop age-related diseases.

Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.