Saturday, November 29, 2008

Research Update: Search for LUCA and RNA

Parallel adaptations to high temperatures in the Archaean eon.

[1] Laboratoire de Biométrie et Biologie Evolutive, CNRS, Université de Lyon, Université Lyon I, 43 Boulevard du 11 Novembre, 69622 Villeurbanne, France [2] These authors contributed equally to this work.

Fossils of organisms dating from the origin and diversification of cellular life are scant and difficult to interpret, for this reason alternative means to investigate the ecology of the last universal common ancestor (LUCA) and of the ancestors of the three domains of life are of great scientific value. It was recently recognized that the effects of temperature on ancestral organisms left 'genetic footprints' that could be uncovered in extant genomes. Accordingly, analyses of resurrected proteins predicted that the bacterial ancestor was thermophilic and that Bacteria subsequently adapted to lower temperatures. As the archaeal ancestor is also thought to have been thermophilic, the LUCA was parsimoniously inferred as thermophilic too. However, an analysis of ribosomal RNAs supported the hypothesis of a non-hyperthermophilic LUCA. Here we show that both rRNA and protein sequences analysed with advanced, realistic models of molecular evolution provide independent support for two environmental-temperature-related phases during the evolutionary history of the tree of life. In the first period, thermotolerance increased from a mesophilic LUCA to thermophilic ancestors of Bacteria and of Archaea-Eukaryota; in the second period, it decreased Nature. 2008 Nov 26. [Epub ahead of print]Click here to read . Therefore, the two lineages descending from the LUCA and leading to the ancestors of Bacteria and Archaea-Eukaryota convergently adapted to high temperatures, possibly in response to a climate change of the early Earth, and/or aided by the transition from an RNA genome in the LUCA to organisms with more thermostable DNA genomes. This analysis unifies apparently contradictory results into a coherent depiction of the evolution of an ecological trait over the entire tree of life.

PMID: 19037246 [PubMed - as supplied by publisher]

Sunday, November 23, 2008

Dr. Thomas Starzl was always known for the way he immersed himself in his work.

In a 1998 article in the New England Journal of Medicine, Starzl and Swiss immunologist and Nobel Prize winner Rolf Zinkernagel proposed that tolerance for a transplanted organ occurs because certain cells in the recipient's immune system that would have attacked the donated organ instead commit suicide, a process known as apoptosis.

They said the same process permits certain infections, such as Hepatitis C, to linger in the body for decades.

Starzl theorizes that in transplantation, this cellular suicide won't occur unless the patient's body is first allowed to mount an immune response to the foreign organ. If that's true, giving patients high amounts of anti-rejection drugs right after a transplant may doom their chances of ever being weaned off the drugs, he said.

Not everyone agrees with Starzl's model, but no researcher contacted was willing to voice his criticisms openly, which may be a testament to the power Starzl still wields in scientific circles.

Starzl himself is convinced that other scientists have come to accept the theory. "The requests for reprints [of the New England Journal paper] have been overwhelming, more than any other [paper] that I can remember," Starzl said. "A lot of people were threatening to write angry letters and criticism, but [the journal] never received one single line."

Great Review of microRNA as Cancer Biomarkers Over at LabSoftNews

"Scientists at Fred Hutchinson Cancer Research Center have discovered that microRNAs molecular workhorses that regulate gene expression (JMG: Who or what is directing genetic traffic lights? Genoanthropology holds RNA) are released by cancer cells and circulate in the blood, which gives them the potential to become a new class of biomarkers to detect cancer at its earliest stages....MicroRNAs, which act as brakes on different parts of a cell, keeping genes in check, have some advantages over protein-based early-detection systems, including that they can be detected potentially in smaller quantities and that the technology exists to rapidly develop microRNA-based early-detection tests"...

Excellent review at Lab Soft News. Pay attention to microRNA research this year.

Friday, November 21, 2008

Discover Magazine's Top 20 Under 40 - Panspermia/RNA World Theory, and Genoanthropology, Plus - Choanoflagellates

Choanocytes, the feeding cells of sponges,
are part of Nicole King's study of early evolution.

Nicole King
Molecular and Cell Biologist, University of California at Berkeley

Nicole King, 38, is hunting for an answer to how the evolutionary leap occurred from single-celled organisms to plants, fungi, multicelled animals, and other forms of life. To find clues, she has trained her sights on choanoflagellates—a group of single-celled eukaryotes thought to be the closest living relatives of animals.

Sequencing the genome of one such organism, King and her colleagues found genes that code for pieces of the same proteins used for the binding of cells and communication between cells in animals —functions that would be unexpected in such an organism. King hypothesizes that proteins that the single-celled ancestors of animals used to interact with the extracellular environment—to capture bacterial prey by binding to their cell surface and to detect chemical signals—were later repurposed to enable cells to stick to and talk to each other. Interpreting the origins of multicellularity is key to understanding the origins of animals, King says, noting that her research “reaches back much further on the family tree than our common ancestors with other primates.” —Y. B.

Edward Boyden
Neuroengineer, MIT Media Lab

Certain species of bacteria and algae have genes that allow them to transform light into electrical energy. Edward Boyden, 29, has been able to show that inserting one of these genes into a neuron can make it similarly responsive. “When we illuminate these cells...we can cause them to be activated,” he says.

Having created such genetically modified neurons, Boyden is engineering brain implants that can stimulate them with light pulses. Boyden’s implants, he hopes, will be used to help control diseases like Parkinson’s, which is sometimes treated with implanted stimulators that issue electric current. “There are things that light can do that purely electric stimulators can’t,” Boyden says. With this technology, researchers can be selective about which neurons they engineer to be responsive, and an optical implant can emit light in a variety of patterns, allowing more precise control over neural circuits. —E. A.

Richard Bonneau
Systems Biologist, New York University

Chronicling the parts of cell anatomy class-style is all well and good, says Richard Bonneau, 33, but biologists’ true holy grail is understanding how each part dictates the function of the others. “You might know that A is related to B, but if you don’t have a dynamic picture of your system, you don’t know which part is affecting which,” he says. “I want to put the arrows on the lines, so to speak.”

By tracking activity in almost all the genes of a free-living archaeon—which, like a bacterium, is a prokaryote—Bonneau was recently able to piece together how the genes affected one another’s expression, enabling him to map the organism’s “control circuit” as if it were a machine. In the process, he found something surprising: Instead of generating completely different responses to external stimuli like light and toxic chemicals, “the archaeon takes those environmental stimuli and puts them into the same integrator,” he says. “There’s not an infinite number of responses.” Knowing the limited range of behaviors that microorganisms display, he adds, will prove a big help in engineering them to churn out drugs and biofuels. —Elizabeth Svoboda

Saturday, November 8, 2008

Genoanthropology Manifesto

Genoanthropology Manifesto
Jen McCabe Gorman
July 2008

NOTE: *This is an intellectual exercise.* In no way should any material in this theory be misconstrued as evidence-based, peer-reviewed, fully researched, or 'credible' science. Also, not sure I believe a word of it, but it's fun to think this far out...

What is Genoanthropology?

A new branch of science, dealing with the semantics and cultural organization of language of life:
Geno (race, offspring) + anthropology (the science of humans) = genoanthropology

  • Arthritic belief in linear development of different lines of science without connecting the dots; bodies of science “omes” in and of themselves reflect conflict-ridden nature of RNA tribes-our behavior is reflection or expression of culture of RNA.
  • Lack of scientific background means I'm free to theorize without boundaries imposed by organizational restraints that some part must be 'right.' Academics care most about their reputation – I don't care about that at all. My tenure doesn't depend on my ability to publish on 'safe' topics. I'm free to be intellectually curious and ideaologically wide-ranging.
The important things:
  • language
  • culture
  • knowledge
  • relationships
  • survival
  • Other species in conflict (viruses, bacteria) plus infighting among tribes of RNA

Developments, study disciplines that mirror/reflect deepening understanding:

  • Faith/ecclesiastical study – creation story, Adam and Eve, Angels, chosen creationism, armageddon and resurrection
  • Conflict – warring tribes, peacemakers – diplomats – geneticists and other genomics scientists chosen?
  • Also sexual antagonism, idea of baby as peace treaty between male/female tribes
  • Software – we're like beta testing – evolution
  • Evolutionary Tree

Related disciplines:
  • evolutionary biology
  • systems biology
  • molecular biology
  • biochemistry
  • genomics (functional genomics, comparative genomics, personal genomics)
  • cultural anthropology/ethnology
  • reproductive studies
  • archeology
  • botany
  • medicine
  • zoology
  • proteomics

  • Human Genome Sciences (The Human Genome Project)
  • Hap Map Project
  • 1,000 Genomes Project
  • Richard Dawkins
  • Dr. Pardis Sabeti, Assistant Professor at Harvard University who focuses on the future of genomics
  • Robert Cook-Deegan, M.D., Duke University
  • Peter Donnelly, Oxford (HapMap Project)
  • Stanford Center for Biomedical Ethics
  • Journals: Cell, Nature, Science, PLos

Central Tenets:
  • RNA is the central factor (RNA World Theory)– organizing DNA and influencing genomics.
  • RNA is organized into clans, tribes. Some of these are at war with each other (sexually antagonistic genes), some are peacemakers and diplomats.
  • A human embryo is, in effect, a peace treaty between warring factions of RNA. The placenta is contributed by the male faction, and the cortex/chordate structure is contributed by the female faction. But the treaty, as with human treaties, often breaks down. The peace process defaults, and the embryo self destructs (miscarriage, birth defects, genetic disorders).
  • We are on an accelerated, fragmenting timeline of evolution. The war is speeding up. We are headed toward armageddon, on both a species and planetary scale. Increased incidences of cancer, war, economic strife, etc.
  • Our understanding of the language of life (genomics), or our lack thereof, determines whether our societies will thrive or collapse into conflict.
  • Our RNA is trying to accelerate our development to ensure its survival – we are “soft spacesuits” for our RNA.
  • The meaning of life isn't humanity. It isn't plants. It isn't oceans, or geographic systems. It is the societies of RNA that live and reproduce and cooperate and war within us. So to ensure the survival of life, we must send out survival pods of RNA into space. This is perhaps how life on this planet began – RNA pods arrived and began replicating, evolving 'software' and 'hardware' that would work in this environment.
  • Human evolution, as with the evolution of most other species, is like our development and beta testing of software. Version 1.0 – design, release, get feedback based on environmental and user interactions, revise. Version 2.0 – repeat the process. Parts of new models are buggy (increased cancer, obesity, asthma rates in children) and parts of old models are obsolete (vestigal tails, wisdom teeth).
  • Our use of faith-based and conflict language (war, battle, creator, common language, etc) reflect the traditions of our RNA. There is a reason we all have a creation story (garden of eden = RNA home world? Adam and Eve are original warring tribes of RNA? God throws them out of the garden, they land on earth, pass down the history of their culture through our myth structure?), all have language abilities, storytelling, other constants. Polytheism and monotheism structures may actually provide links to WHICH tribes of humans carry which tribes of other words we believe what our RNA believe.
  • 50k major gene "families?" Craig Venter @ Ted
  • Everyone's worried about scaling up for population-based health research – to better understand population-based impacts of genomics on communities (begin paying more attention to health as related to place, situation within community and cultural heirarchies and family groups) we must actually scale DOWN – as Watson and Crick did when looking at crystallization in radiographs that revealed double helix structure as DNA – only with that microexamination was a marcroexamination like that of the Human Genome Sequencing Project made possible.
  • We are patenting genes for breast cancers in the US. This is kind of like slavery – we don't 'own' the same gene in everyone and we certainly don't own genetic sequences. Genomic sequences are NOT intellectual property or corporate capital...they are living entities.
  • Our RNA tribes are at war with eachother, and we reflect infighting, but they're also in conflict with other species, defending the host cities (us) from interlopers such as viruses. Recent research on viral spread suggests waves of attack, much as humans and animals mount attacks using limited resources. They may also have a 'home base' in the tropics: “For starters, the viral diversity peaks in winter in both regions, which means the peak is offset by six months. But the peaks show a distinct pattern, as all the viruses are variations of either H3/N2 or H1/N1—you never get both types of virus in the same year. The peaks seem to correlate in the different hemispheres, although there's limited overlap in the data. To the authors, this suggests that there's a viral reservoir in the tropics, and only a single type of virus winds up successfully spreading from it in a given year.”
  • Genoanthropological developments will be collaborative, interdepartmental, cross-pollinating knowledge and curious inquiry from all developments and sectors – truly open-source science, or science 2.0: ““Possibly the most important of these past lessons is that social movements may emerge organically but often do not succeed until at least some primitive form of organization or basic structure takes form around which resources, supporters, and eventually the general public, can coalesce."

More Research Links

Humans Less Genetically Diverse Than Thought given antagonistic history of our species.

Could all noncoding DNA be functional? Is "junk" DNA more than junk? Look up Hologenomics = genomics+epogenomics expressed in informatics.

Wired for Sex: The Neurobiology of Fruit Fly Mating Decisions

Genes and Social Behavior

Systems Biology: Ready or Not? Is a systems approach useful? Computational power and informatics gives potential to the systems view, but is it being harnessed?

New Research of Interest

[RNA interference as antiviral strategy]
[Article in German]
Neumann-Haefelin C, Blum HE, Thimme R.
Abteilung Innere Medizin II, Universitätsklinikum Freiburg.
RNA interference is the inhibition of gene expression at the level of messenger RNA (mRNA) mediated by small RNA molecules. Small interfering RNA (siRNA) is an important immune defence mechanism in plants and non-vertebrates. In addition, synthetic siRNAs can be used to inhibit gene expression also in human cells. More than 500 microRNAs (miRNAs), however, are involved in the natural regulation of gene expression in humans, e. g., in development-specific gene expression in embryogenesis or organ development. Although a role of miRNAs in antiviral immune defence has been discussed for some time, only recently virus-promoting as well as antiviral properties of defined miRNAs have been identified in hepatitis C virus (HCV) infection. The understanding of the mechanisms of action of miRNA might lead to new antiviral and preventive strategies.
PMID: 18988133 [PubMed - in process]

: Genetica. 2008 Sep;134(1):5-19. Epub 2007 Jul 7.
The genetic basis of traits regulating sperm competition and polyandry: can selection favour the evolution of good- and sexy-sperm?
Evans JP, Simmons LW.
Centre for Evolutionary Biology, School of Animal Biology M092, The University of Western Australia, Nedlands, WA, Australia.
The good-sperm and sexy-sperm (GS-SS) hypotheses predict that female multiple mating (polyandry) can fuel sexual selection for heritable male traits that promote success in sperm competition. A major prediction generated by these models, therefore, is that polyandry will benefit females indirectly via their sons' enhanced fertilization success. Furthermore, like classic 'good genes' and 'sexy son' models for the evolution of female preferences, GS-SS processes predict a genetic correlation between genes for female mating frequency (analogous to the female preference) and those for traits influencing fertilization success (the sexually selected traits). We examine the premise for these predictions by exploring the genetic basis of traits thought to influence fertilization success and female mating frequency. We also highlight recent debates that stress the possible genetic constraints to evolution of traits influencing fertilization success via GS-SS processes, including sex-linked inheritance, nonadditive effects, interacting parental genotypes, and trade-offs between integrated ejaculate components. Despite these possible constraints, the available data suggest that male traits involved in sperm competition typically exhibit substantial additive genetic variance and rapid evolutionary responses to selection. Nevertheless, the limited data on the genetic variation in female mating frequency implicate strong genetic maternal effects, including X-linkage, which is inconsistent with GS-SS processes. Although the relative paucity of studies on the genetic basis of polyandry does not allow us to draw firm conclusions about the evolutionary origins of this trait, the emerging pattern of sex linkage in genes for polyandry is more consistent with an evolutionary history of antagonistic selection over mating frequency. We advocate further development of GS-SS theory to take account of the complex evolutionary dynamics imposed by sexual conflict over mating frequency.
PMID: 17619174 [PubMed - indexed for MEDLINE]