The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation ofobresults in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.

Universal trees based on sequences of single gene homologs cannot be rooted. Iwabe et al. [Iwabe, N., Kuma, K.-I., Hasegawa, M., Osawa, S. & Miyata, T. (1989) Proc. Natl. Acad. Sci. USA 86, 9355-9359] circumvented this problem by using ancient gene duplications that predated the last common ancestor of all living things. Their separate, reciprocally rooted gene trees for elongation factors and ATPase subunits showed Bacteria (eubacteria) as branching first from the universal tree with Archaea (archaebacteria) and Eucarya (eukaryotes) as sister groups. Given its topical importance to evolutionary biology and concerns about the appropriateness of the ATPase data set, an evaluation of the universal tree root using other ancient gene duplications is essential. In this study, we derive a rooting for the universal tree using aminoacyl-tRNA synthetase genes, an extensive multigene family whose divergence likely preceded that of prokaryotes and eukaryotes. An approximately 1600-bp conserved region was sequenced from the isoleucyl-tRNA synthetases of several species representing deep evolutionary branches of eukaryotes (Nosema locustae), Bacteria (Aquifex pyrophilus and Thermotoga maritima) and Archaea (Pyrococcus furiosus and Sulfolobus acidocaldarius). In addition, a new valyl-tRNA synthetase was characterized from the protist Trichomonas vaginalis. Different phylogenetic methods were used to generate trees of isoleucyl-tRNA synthetases rooted by valyl- and leucyl-tRNA synthetases. All isoleucyl-tRNA synthetase trees showed Archaea and Eucarya as sister groups, providing strong confirmation for the universal tree rooting reported by Iwabe et al. As well, there was strong support for the monophyly (sensu Hennig) of Archaea. The valyl-tRNA synthetase gene from Tr. vaginalis clustered with other eukaryotic ValRS genes, which may have been transferred from the mitochondrial genome to the nuclear genome, suggesting that this amitochondrial trichomonad once harbored an endosymbiotic bacterium.

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus-traceable to a Late Miocene, chimpanzee-like morphology-shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size and emigration of Homo from Africa. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.

Blue Gene is an IBM project aimed at designing supercomputers that can reach operating speeds in the petaFLOPS (PFLOPS) range, with low power consumption. The project created three generations of supercomputers, Blue Gene/L, Blue Gene/P, and Blue Gene/Q. During their deployment, Blue Gene systems often led the TOP500 and Green500 rankings of the most powerful and most power-efficient supercomputers, respectively. Blue Gene systems have also consistently scored top positions in the Graph500 list. The project was awarded the 2009 National Medal of Technology and Innovation.As of 2015, IBM appears to have ended development of the Blue Gene family, though no formal announcement has been made. IBM has since focused its supercomputer efforts on the OpenPower platform, using accelerators such as FPGAs and GPUs to address the diminishing returns of Moore's law. History In December 1999, IBM announced a US$100 million research initiative for a five-year effort to build a massively parallel computer, to be applied to the study of biomolecular phenomena such as protein folding. The project had two main goals...

Summary. The four disparate images shown in Figure 1 have this in common: each represents a radical adaptation that would not have happened had lateral gene transfer (LGT), also known as horizontal gene transfer (HGT), not been the powerful evolutionary force we now know it to be. Those who study the phenomenon are still struggling to quantitatively assess LGT as a process or processes and accommodate its implications for how patterns in nature should be represented - such as the existence of definable species or a meaningful universal Tree of Life. But all agree that the exchange of genetic information across species lines - which is how we will define LGT in this primer - is far more pervasive and more radical in its consequences than we could have guessed just a decade ago. Both prokaryotes (bacteria and archaea) and eukaryotes have experienced LGT, though its potential as a source of novel adaptations and as a challenge to phylogenetics are so far more obvious and better understood for prokaryotes, as are the mechanisms by which it is effected.

Gene therapy is a medical technology which aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I. In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as Glybera (2012), Strimvelis (2016), Kymriah (2017), Luxturna (2017), Onpattro (2018), Zolgensma (2019), Abecma (2021), Adstiladrin, Roctavian and Hemgenix (all 2022). Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ...

A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly landscaper genes regulate growth by contributing to the surrounding environment, when mutated can cause an environment that promotes unregulated proliferation. The classification schemes are evolving as medical advances are being made from fields including molecular biology, genetics, and...

Gene Budig built an amazing resume before moving to Charleston and joining the RiverDogs' ownership group 14 years ago. He was a college president at Illinois State, West Virginia and

The nearly neutral theory contends that the interaction of drift and selection is important and occurs at various levels, including synonymous and nonsynonymous substitutions in protein coding regions and sequence turnover of regulatory elements. Recent progress of the theory is reviewed, and the interaction between drift and selection is suggested to differ at these different levels. Weak selective force on synonymous changes is stable, whereas its consequence on nonsynonymous changes depends on environmental factors. Selection on differentiation of regulatory elements is even more dependent on environmental factors than on amino acid changes. Of particular significance is the role of drift in the evolution of gene regulation that directly participates in morphological evolution. The range of near neutrality depends on the effective size of the population that is influenced by selected linked loci. In addition to the effective population size, molecular chaperones such as heat shock protein 90 have significant effects on the range of near neutrality.