The pronoun ‘I’ is becoming obsolete

Don't look now, but the pronoun "I" is becoming obsolete. Recent microbiological research has shown that thinking of plants and animals, including humans, as autonomous individuals is a serious over-simplification.

Tree of life created with bacterial cultures [Credit: Robert Brucker/
Harvard University]

A series of groundbreaking studies have revealed that what we have always thought of as individuals are actually "biomolecular networks" that consist of visible hosts plus millions of invisible microbes that have a significant effect on how the host develops, the diseases it catches, how it behaves and possibly even its social interactions.

"It's a case of the whole being greater than the sum of its parts," said Seth Bordenstein, associate professor of biological sciences at Vanderbilt University, who has contributed to the body of scientific knowledge that is pointing to the conclusion that symbiotic microbes play a fundamental role in virtually all aspects of plant and animal biology, including the origin of new species.

In this case, the parts are the host and its genome plus the thousands of different species of bacteria living in or on the host, along with all their genomes, collectively known as the microbiome. (The host is something like the tip of the iceberg while the bacteria are like the part of the iceberg that is underwater: Nine out of every 10 cells in plant and animal bodies are bacterial. But bacterial cells are so much smaller than host cells that they have generally gone unnoticed.)

Microbiologists have coined new terms for these collective entities -- holobiont -- and for their genomes -- hologenome. "These terms are needed to define the assemblage of organisms that makes up the so-called individual," said Bordenstein.

In the article "Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes" published online Aug. 18 in the open access journal PLOS Biology, Bordenstein and his colleague Kevin Theis from the University of Michigan take the general concepts involved in this new paradigm and break them down into underlying principles that apply to the entire field of biology.

They make specific and refutable predictions based on these principles and call for other biologists to test them theoretically and experimentally.

"One of the basic expectations from this conceptual framework is that animal and plant experiments that do not account for what is happening at the microbiological level will be incomplete and, in some cases, will be misleading as well," said Bordenstein.

The first principle they advance is that holobionts and hologenomes are fundamental units of biological organization.

Another is that evolutionary forces such as natural selection and drift may act on the hologenome not just on the genome. So mutations in the microbiome that affect the fitness of a holobiont are just as important as mutations in the host's genome. However, they argue that this does not change the basic rules of evolution but simply upgrades the types of biological units that the rules may act upon.

Although it does not change the basic rules of evolution, holobionts do have a way to respond to environmental challenges that is not available to individual organisms: They can alter the composition of their bacterial communities. For example, if a holobiont is attacked by a pathogen that the host cannot defend against, another symbiont may fulfill the job by manufacturing a toxin that can kill the invader. In this light, the microbes are as much part of the holobiont immune system as the host immune genes themselves.

According to Bordenstein, these ideas are gaining acceptance in the microbiology community. At the American Society of Microbiology General Meeting in June, he convened the inaugural session on "Holobionts and Their Hologenomes" and ASM's flagship journal mBio plans to publish a special issue on the topic in the coming year.

However, adoption of these ideas has been slower in other fields.

"Currently, the field of biology has reached an inflection point. The silos of microbiology, zoology and botany are breaking down and we hope that this framework will help further unify these fields," said Bordenstein.

Not only will this powerful holistic approach affect the basic biological sciences but it also is likely to impact the practice of personalized medicine as well, Bordenstein said.

Take the missing heritability problem, for example. Although genome-wide studies have provided valuable insights into the genetic basis of a number of simple diseases, they have only found a small portion of the genetic causes of a number of more complex conditions such as autoimmune and metabolic diseases.

These may in part be "missing" because the genetic factors that cause them are in the microbiome, he pointed out.

"Instead of being so 'germophobic,' we need to accept the fact that we live in and benefit from a microbial world. We are as much an environment for microbes as microbes are for us," said Bordenstein.

Author: David Salisbury | Source: Vanderbilt University [August 20, 2015]

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Research helps answer how birds got their beaks

Birds are among the most successful creatures on the planet, with more than 10,000 species living across the globe, occupying a dizzying array of niches and eating everything from large animals to hard-to-open nuts and seeds. Part of the key to that success, scientists say, might be right in front of their faces.

“Because we can get live alligator embryos with snouts, we can actually compare them
 with beaked modern birds to see how they develop their faces, and what genes are
 activating during that process,” said Arkhat Abzhanov, who led a team of 
researchers who found that bird beaks are the result of skeletal changes 
controlled by two genetic pathways [Credit: Abzhanov Lab]

Led by Arkhat Abzhanov, a former associate professor of organismic and evolutionary biology, a team of researchers has shown that bird beaks are the result of skeletal changes controlled by two genetic pathways, shedding light on the origins of one of nature's most efficient tools. The study was described in a paper published earlier this year in the journal Evolution.

"The evolution of the beak was a seminal step for modern birds that made them distinct from primitive birds who still had snouts," Abzhanov said. "With this paper we wanted to understand that process in mechanistic terms."

The first step toward answers, Abzhanov said, was to clarify why birds have beaks at all.

"The immediate ancestors of birds had very long fingers and a somewhat opposable thumb," he said. "It's believed they could use their hands to build nests and manipulate small prey … and that's exactly what birds lost when they evolved wings—those fingers became bones in the wing. So once birds lost them, they replaced them with a finger on their face—the beak.

"Both the upper and lower beak can move, so it works like pincers, allowing a level of accuracy in handling and manipulating objects you can only achieve with fingers. I like to show my students a video of weaver birds, which use long grasses to weave nests, and even tie real knots during construction. You cannot do that with a snout."

To get an up-close-and-personal view of how developmental patterns reveal the evolution of birds, Abzhanov and colleagues turned to their closest living relative—the alligator, a crocodilian.

"Because we can get live alligator embryos with snouts, we can actually compare them with beaked modern birds to see how they develop their faces, and what genes are activating during that process," Abzhanov said.

The team discovered two genetic pathways, both of which are present in virtually all vertebrates, but which work differently in the development of bird faces.

These signaling pathways, FGF8 and WNT, tell cells how to proliferate and differentiate, and in land vertebrates are normally expressed in two regions, around the left and right nasal pits. In birds, however, expression also occurs in the middle of the face, causing the two regions to fuse to produce a single beak bone instead of paired facial bones.

"We later found that FGF8 mediates the expression of WNT," Abzhanov said. "So the critical molecule in this entire story is FGF8. It's expressed very early, and only transiently, but this change, this novel medial expression of FGF8, coincides with the appearance of the beak in modern birds."

For insight into beak development, Abzhanov and colleagues interrupted the pathways in chickens, producing embryos with facial bones that looked remarkably like their snouted dinosaur ancestors.

"What happened is we got a range of phenotypes," Abzhanov said. "Some looked fairly normal, and others were very different. In some embryos the bones that make up the beak did not fuse properly and developed more blunt shapes."

The results of the study, he said, indicate that beaks did not emerge fully formed, but developed gradually through intermediate shape changes, some of which are yet to be found in the fossil record.

"We suggest paleontologists will be able to find fossils in the future which will bridge this gap between beaked modern birds and their snouted ancestors," Abzhanov said. "That transition may have happened in an isolated geographic area, or may have happened very quickly, so they may be hard to find, but we predict that such transitional fossils will eventually be recovered and they will match some of our experimental animals."

He added: "What's important is we can now explain an important characteristic of the face unique to modern birds, an example of an evolutionary novelty."

Author: Peter Reuell | Source: Harvard University [August 19, 2015]

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Key genetic event underlying fin-to-limb evolution

A study of catsharks reveals how alterations in the expression and function of certain genes in limb buds underlie the evolution of fish fins to limbs. The findings are reported by researchers from Tokyo Institute of Technology (Tokyo Tech), the Centre for Genomic Regulation (CRG, Barcelona) and their collaborators in the journal eLife and give new insight into how fish evolved to live on land in the form of early tetrapods.

This is a model of the fin-to-limb evolution. A gradual shift of the balance of anterior 
(green) and posterior (blue) field might have led to the evolution from fins into limbs 
[Credit: Mikiko Tanaka/Tokyo Institute of Technology]

The first four-legged, land-living creatures -- known as early tetrapods -- evolved from fish, following the transformation of fins into limbs. This fin-to-limb evolution is a crucial, yet so far unsolved, example of how morphological changes can dramatically alter life on Earth. Now, researchers at Tokyo Tech and CRG, together with scientists across Japan and Spain, have revealed how genetic alterations governing the patterning of skeletal structures in fins may have led to the evolution of limbs and the rise of early tetrapods.

The forelimbs of tetrapod evolved from the pectoral fins of the ancestral fish. These fins contain three or more basal bones connected to the pectoral (shoulder) girdle. However, the most of basal bones located in the anterior side (i.e. the thumb side in the human limb) were lost in early tetrapods, and only the most posterior bone remained as the "humerus (i.e. the upper arm of humans)."

Pectoral fins of catsharks also contain three basal bones as seen in the ancestral fish. Thus, the team examined the fin development of catsharks, and revealed that there was a shift in the balance of anterior (thumb side) and posterior (pinky side) fields in their fin buds compared to that in mouse limb buds.

A key regulator protein controlling the balance of anterior and posterior fields of limb buds of tetrapods is Gli3. This protein is expressed in the anterior part of limb buds, and regulates the expression of a number of genes providing cells with information about their position along the anterior-posterior axis. For example, Alx4 and Pax9 are expressed in a small area of the anterior part of the limb bud, while Hand2 is expressed in a large area of the posterior field.

To determine whether shifts in the balance of anterior and posterior field occurred during fin-to-limb evolution, Onimaru, postdoctoral researcher currently at Sharpe's lab (CRG), and his colleagues carefully compared the expression, function and regulation of genes involved in anterior-posterior patterning in pectoral fins of catsharks, with those of mice. They found that, in pectoral fin of catshark embryos, Gli3 expression was intensified posteriorly, and the balance of the anterior and posterior fields was shifted. This indicates that a major genetic shift (posteriorisation) occurred as tetrapods evolved.

Furthermore, they found that the catshark genome lacked a sequence found in mice and other tetrapods, which is responsible for preventing Gli3 expression in the posterior part of tetrapod limb buds. As a known repressor, the restriction of Gli3 to the anterior may result in the loss of skeletal structure in this domain. When the researchers experimentally "posteriorised" pectoral fin buds of catsharks, the fins lost anterior skeletal elements, and showed a single bone connected to the pectoral girdle, as seen in fossil Tiktaalik pectoral fins.

These results suggest that one of the key genetic events during the fin-to-limb evolution was a shift of the balance of the anterior and posterior fields (a "posteriorisation") and loss of anterior skeletal elements. Further research involving genome-wide studies, particularly into the role of Gli3, will help explore these results more fully.

Source: Center for Genomic Regulation [August 19, 2015]

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The Tree of Life — more like a bush

New species evolve whenever a lineage splits off into several. Because of this, the kinship between species is often described in terms of a 'tree of life', where every branch constitutes a species. Now, researchers at Uppsala University have found that evolution is more complex than this model would have it, and that the tree is actually more akin to a bush.

The kinship between species is often described in terms of a ‘tree of life’, where every
 branch constitutes a species. Now, researchers have found that the tree is actually
 more akin to a bush [Credit: Uppsala University]

Less than a year ago, a consortium of some hundred researchers reported that the relationship between all major bird clades had been mapped out by analysing the complete genome of around 50 bird species. This included the exact order in which the various lineages had diverged.

Since then, two of the members of the consortium, Alexander Suh and Hans Ellegren at the Uppsala University Evolutionary Biology Centre, have expanded upon this model by analysing the avian genome through a new method, which hinges on so-called 'jumping genes'. Their results, published in PLOS Biology,  paint a partially contrasting picture of the kinship between the various species.

'We can see that the very rapid rate at which various bird species started evolving once the dinosaurs went extinct, i.e. around 65 million years ago, meant that the genome failed to split into separate lineages during the process of speciation', Hans Ellegren says.

This is because evolution moved quickly, and many species arose in quick succession. When this happens, different parts of the genome can tell disparate tales of the kinship between the new species. The phenomenon has previously been explained theoretically and is a result of the genetic variation passing from one species to another. If new species then continue to evolve quickly, random chance can end up determining which original genetic variants end up in each lineage. The phenomenon is called incomplete lineage sorting.

'Previously, the difficulty resided in finding instances of incomplete lineage sorting far back in time', Hans Ellegren says. 'Therefore, it's been unknown if this phenomenon has affected evolution to any appreciable extent'.

By using the jumping genes, or so-called retrotransposed elements, the Uppsala researchers have found that, for instance, a cuckoo can be more closely related to a hummingbird than a pigeon in a certain part of its genome, while the opposite holds true in another part. The study found numerous examples to corroborate the existence of the phenomenon.

This is one of the first cases in evolutionary research where researchers have been able to document and quantify incomplete lineage sorting far back in time. It is likely a far more common occurrence than previously thought.

'The more complex kinship patterns that result from this phenomenon mean that the Tree of Life should often be understood as a Bush of Life', Alexander Suh and Hans Ellegren say.

Author: Linda Koffmar | Source: Uppsala University [August 18, 2015]

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Is nature mostly a tinkerer or an inventor?

The Kruppel-like factor and specificity protein (KLF/SP) genes are found across many species, ranging from single cell organisms to humans. This gene family has been conserved during evolution, because it plays a vital role in regulating the expression of other genes. Understanding the evolutionary history of the KLF/SP gene family may shed light on major events in animal evolution and perhaps help discern some of the molecular mechanisms associated with certain human diseases, including many cancers.

The KLF/SP protein domain co-occurrence network map is depicted in the center. The domain network map is encircled by a phylogenetic tree depicting branching relationships for some of the phyla used in the study. Images (with photo credit) clockwise from the lower right; Monosiga brevicollis (photo by Stephan Fairclough/CC BY 2.5), Mnemiopsis leidyi (photo by William E. Browne), Echinoclathria dichotoma (photo by Pbsouthwood/CC BY 3.0), Nematostella vectensis (photo by William E. Browne), Homo sapiens (photo by William E. Browne), Branchiostoma lanceolatum (photo by Hans Hillewaert/CC BY 4.0), Drosophila melanogaster (photo by William E. Browne), and Scolelepis squamata [Credit: Hans Hillewaert]

By closely examining the genomes of 48 species, biologists from the University of Miami (UM) College of Arts & Sciences have revealed the timing and mechanisms underlying the expansion and diversification of the KLF/SP gene family, which is known to regulate the maintenance of stem cells. Their study shows that, while the origin of the KLF/SP gene family predates the origins of animals well over 600 million years ago, the expansion of the gene family and increasing cell type diversity in animals happened concurrently.

"Our study paints a picture of nature innovating largely through sharing the functional bits of genes—tinkering with molecular genetic material that already exists," said William E. Browne, assistant professor of Biology at UM's College of Arts & Sciences and principal investigator of the study.

The KLF/SP genes, like other protein coding genes, contain codes for specific combinations of protein segments called domains. To explain the relationship between genes and domains that they encode, Browne likens a gene to a sentence and domains to the words the sentence contains.

"A gene (the sentence) typically performs multiple functions and often each of those functions can be associated with a discrete domain (a word)," Browne said. "Typically a gene carries out a series of functions based upon the combination and arrangement of the discrete domains it encodes," he said. "It is this collection of domains, corresponding to functions that define a gene's 'activity' or role within a cell."

The analysis reveals that the primary mechanisms for the expansion and diversification of the KLF/SP gene family, during evolution of animals occurred as a complex intersection of domain shuffling (where segments of a gene that code for specific domains are shuffled between genes during evolution), gene duplication (the process by which an entire gene is duplicated), and de novo domain evolution (the emergence of gene sequences with novel functional protein domains).

This domain-centric approach is one of the unique aspects of the current study.

"By identifying the independent evolutionary trajectories of each domain, we were able to show that diversification of the KLF/SP gene family was accompanied by the acquisition of additional protein-protein interaction domains," said Jason S. Presnell, Biology Ph.D. student at UM's College of Arts & Sciences and first author of the study. "Most of these domains were already present in other genes and were likely acquired by KLF/SP genes via recombination."

KLF/SP genes belong to an important class of genes, called transcription factors, which either turn on or turn off the expression of other genes. The findings show a clear increase in repressor domains (domains that turn off the expression of other genes) as the KLF/SP gene family has expanded. This expansion mirrors increases in cell type diversity among animals and demonstrates that the transition from single-cell life to multicellular life occurred largely by "tinkering" with existing genes.

"This is interesting because it supports the idea that the appearance of new types of cells in a lineage of organisms as they evolve may be, more commonly, a consequence of turning off genes in unique temporal and spatial combinations," Browne said. "Large numbers of unique cell types are required to support the development of complex tissues and organs."

For the study, the researchers looked at 48 different genomes ranging from plants; single celled organisms including slime molds, fungi, and choanoflagellates; early branching multicellular animals including ctenophores, sponges, and jellyfish; invertebrates including insects and sea urchins; to vertebrates such as sharks, fish, and mammals including humans.

"This was the first study to examine the evolutionary history of the KLF/SP gene family on such a broad scale," Presnell said. "We are hopeful that our continuing experiments will help illuminate the ancestral functions of these important genes and provide some insight into the critical transition from single celled life to animal multicellularity."

The study is published in the journal Genome Biology and Evolution. Christine E. Schnitzler from the National Human Research Institute, National Institutes of Health, is co-author of the study. The researchers are now developing strategies for assessing the function of these genes in the comb jelly Mnemiopsis leidyi, an important model system for exploring the early evolution of animals.

Source: University of Miami [August 18, 2015]

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