Nov 23, 2015 07:28 AM
(This post was last modified: Nov 23, 2015 07:39 AM by C C.)
Sensory illusion causes cells to self-destruct
RELEASE: Magic tricks work because they take advantage of the brain's sensory assumptions, tricking audiences into seeing phantoms or overlooking sleights of hand. Now a team of UC San Francisco researchers has discovered that even brainless single-celled yeast have sensory biases that can be hacked by a carefully engineered illusion, a finding that could be used to develop new approaches to fighting diseases such as cancer.
"The ability to perceive and respond to the environment is a basic attribute of all living organisms, from the greatest to the smallest," said Wendell Lim, PhD, the study's senior author. "And so is the susceptibility to misperception. It doesn't matter if the illusion is based on molecular sensors within a single cell or neurons in the brain."
In the new study, published online Nov. 19, 2015 in Science Express, Lim and his team discovered that yeast cells falsely perceive a specifically timed pattern of stress -- caused by alternating between low and mildly increased sodium levels -- as a massive, continuously increasing ramp of stress. In response, the microbes end up over-responding and killing themselves. The results, Lim says, suggest a whole new way of looking at the perceptual abilities of simple cells and could even be used to develop new approaches to fighting diseases using the power of illusion.
Timing of stress response is yeast cells' 'Achilles heel'
"This discovery was a bit of an accident actually," said Lim, chair of the Department of Cellular and Molecular Pharmacology at UCSF, director of the UCSF Center for Systems and Synthetic Biology, and a Howard Hughes Medical Institute (HHMI) investigator. "We were interested in the general issue of how cells interpret information over time. Frequency is a key aspect of all our communications, whether it's hearing language or transmitting radio signals, but do cells themselves use this kind of information? It's something we don't know much about."
To explore this question, two postdoctoral fellows in Lim's lab, Ping Wei, PhD, now at Peking University School of Life Sciences, and Amir Mitchell, PhD, set up a system that allowed them to expose yeast to a mild stressor -- a small increase in salt in the yeast's environment -- and to oscillate between the increased salt level and the baseline level at different frequencies.
Normally, sensor molecules in a yeast cell detect changes in salt concentration and instruct the cell to respond by producing a protective chemical. After this transient response, the cell can resume growing happily as if conditions had not changed. The researchers found that the cells were perfectly capable of adapting when they flipped the salt stress on and off every minute or every 32 minutes. But to their surprise, when they tried an eight-minute oscillation of precisely the same salt level the cells quickly stopped growing and began to die off.
"That was just a jaw-dropping moment," said Mitchell. "These cells should be able to handle this level of osmotic stress, but at one particular frequency they just go haywire. We'd never seen anything like this before."
Could sensory illusions be used to fight cancer?
Mitchell, who was first author on the new study, went on to inspect the cellular mechanism underlying this unexpected, frequency-dependent toxicity. Using mathematical modeling and experiments in which he tweaked the molecular wiring of the mitogen activated protein kinase (MAPK) pathway that mediates the cells' salt-sensing system, he revealed a sensory misperception: Because of the way the MAPK pathway is set up, the cells interpret an eight-minute oscillation as an ever-increasing staircase of salt concentration. This leads to excessive activation of the cells' protective response, and ultimately to their death (see Movie).
"Why would these cells have evolved this bizarre sensitivity to salt oscillations?" Mitchell asked. "Well, we don't think that they did. It's just a side effect of the fact that the molecular signaling network yeast cells use to mediate this stress response was optimized for their natural environment, in which salt stress normally occurs in a gradually increasing ramp -- like if the yeast is sitting on a grape as morning dew slowly evaporates. It's this assumption on the part of the yeast -- their anticipation that the stress will keep getting more severe -- that creates their Achilles heel."
The study suggests that many cell types, including human cells, may be predisposed to misperceptions and could be fooled by carefully engineered illusions. For instance, Mitchell said, the signaling pathway by which human cancer cells respond to chemical growth factors is closely related to the stress-sensing MAPK pathway in yeast. Thus, identification of cell-specific misperceptions might ultimately be exploited to induce cancer cells to kill themselves, he suggested, while minimally harming healthy, neighboring cells.
"On its own, this is a humble finding," Lim said, but he believes it has broader implications for biomedical research. "Like us, cells have biased perceptions based on what environmental patterns they've evolved with. By understanding these biases, we can modulate their behavior," he said. "In particular, it's striking to realize how important the time domain is for cells. The temporal pattern with which we present any stimulus, whether it's salt concentrations, drugs or beams of light, may make all the difference."
Our closest wormy cousins: About 70% of our genes trace their ancestry back to the acorn worm
RELEASE: A team from the Okinawa Institute of Science and Technology Graduate University (OIST) and its collaborators has sequenced the genomes of two species of small water creatures called acorn worms and showed that we share more genes with them than we do with many other animals, establishing them as our distant cousins.
The study found that 8,600 families of genes are shared across deuterostomes, a large animal grouping that includes a variety of organisms, ranging from acorn worms to star fishes, from frogs to dogs, to humans. This means that approximately 70% of our genes trace their ancestry back to the original deuterostome. By comparing the genomes of acorn worms to other animals, OIST scientists inferred the presence of these genes in the common ancestor of all deuterostomes, an extinct animal that lived half a billion years ago. This research shows that the pharyngeal gene cluster is unique to the deuterostomes and it could be linked to the development of the pharynx, the region that links the mouth and nose to the esophagus in humans. These findings were published in Nature, summarizing an international collaboration between OIST researchers and teams from the US, UK, Japan, Taiwan and Canada.
Around 550 million years ago, a great variety of animals burst onto the world in an event known as the Cambrian explosion. This evolutionary radiation revealed several new animal body plans, and changed life on Earth forever, as complex animals with specialized guts and behavioural features emerged. Thanks to the genome sequencing of multiple contemporary animals of the deuterostome group, we can go back in time to unveil aspects of the long-lost ancestor of this diverse group of animals.
Acorn worms are marine creatures that live on the ocean floor and feed by filtering a steady flow of sea water through slits in the region of their gut between mouth and esophagus. These slits are distantly related to the gills of fish, and represent a critical innovation in evolution not shared with animals like flies or earthworms. Since acorn worms occupy such a critical evolutionary position relative to humans the researchers sequenced two distantly related acorn worm species, Ptychodera flava, collected in Hawaii, and Saccoglossus kowalevskii, from the Atlantic Ocean. "Their genomes are necessary to fill the gap in our understanding of the genes shared by the common ancestor of all deuterostomes," explains Dr Oleg Simakov, lead author of this study.
Indeed, beyond sequencing these two organisms, the team was also interested in identifying ancient gene families that were already present in the deuterostome ancestor. The team compared the genomes of the two acorn worms with the genomes of 32 diverse animals and found that about 8,600 families of genes are homologous, that is, evolutionarily-related, across all deuterostomes and so are confidently inferred to have been present also in the genome of their deuterostome ancestor. Human arms, birds' wings, cats' paws and the whales' flippers are classical examples of homology, because they all derive from the limbs of a common ancestor. As with anatomical structures, genes homology is defined in terms of shared ancestry. Because of later gene duplications and other processes, these 8,600 homologous genes correspond to at least 14,000 genes, or approximately 70%, of the current human genome.
The study also identified clusters of genes that are close together in acorn worm genomes and in the genomes of humans and other vertebrates. The ancient proximity of these gene clusters, preserved over half a billion years, suggests that the genes may function as a unit. One gene cluster connected with the development of the pharynx in vertebrates and acorn worms is particularly interesting. It is shared by all deuterostomes, but not present in non-deuterostome animals such as insects, octopuses, earthworms and flatworms. The pharynx of acorn worms and other animals functions to filter food and to guide it to the digestive system. In humans, this cluster is active in the formation of the thyroid glands and the pharynx. Scientists suggest there is a connection between the function of the modern thyroid and the filter feeding mechanism of acorn worms. This pharyngeal gene cluster contains six genes ordered in a common pattern in all deuterostomes and includes the genes for four proteins that are critical transcriptional regulators that control activation of numerous other genes. Genes ordered in the same way and located next to each other in the chromosomal DNA are linked and transferred together from one generation to the next. Interestingly, not only the DNA that codes for these transcription factor genes is shared among the deuterostomes, but also some of the DNA pieces that are used as binding sites for the transcription factors are conserved among these animals.
"Our analysis of the acorn worm genomes provides a glimpse into our Cambrian ancestors' complexity and supplies support for the ancient link between the pharyngeal development and the filter feeding life style that ultimately contributed to our evolution," explains Dr Simakov.
Acorn worm genome reveals gill origins of human pharynx: Earliest animals with gill slits tell biologists about origin of swallowing, speaking
RELEASE: The newly sequenced genomes of two marine worms are shedding light on the 570 million-year evolution of gills into the pharynx that today gives humans the ability to bite, chew, swallow and speak.
The draft genome sequences of two species of acorn worm, which live in U-shaped burrows in shallow, brackish water, are the first genomes of hemichordates, which retain similarities to the first animals to evolve pharyngeal or "gill" slits. Those ancestors eventually gave rise to chordates: animals with backbones and hollow nerve cords, like humans and other vertebrates.
Since acorn worms and the human lineage diverged 570 million years ago, pharyngeal slits for filtering food evolved into gills for extracting oxygen, and later into today's human upper and lower jaw and pharynx, which encompasses the thyroid gland, tongue, larynx (voice box) and various glands and muscles between the mouth and the throat. Humans and other terrestrial vertebrates actually initiate vestigial gills while embryos, though they disappear quickly and rarely persist in infants.
"The presence of these slits in acorn worms and vertebrates tells us that our last common ancestor also had them, and was likely a filter feeder like acorn worms today," said Daniel Rokhsar, one of the leaders of the sequencing effort and a UC Berkeley professor of molecular and cell biology and of physics. "Acorn worms are marine invertebrates that, despite their decidedly non-vertebrate form, are nevertheless among our closest invertebrate relatives."
"It's an ugly beast," acknowledged John Gerhart, senior author of the report and a professor of the graduate school at UC Berkeley. "Acorn worms look very different from chordates, which makes it especially surprising that they and chordates, like humans, are so similar on the genomic, developmental and cell biological levels."
In fact, about 70 percent of human genes have counterparts in the acorn worms, suggesting that these are ancient genes inherited from the common ancestor.
The research group included scientists from UC Berkeley; the Okinawa Institute of Science and Technology Graduate University in Onna, Okinawa, Japan; Stanford University's Hopkins Marine Station; the Baylor College of Medicine in Texas and the United Kingdom. They published their findings in the Nov. 19 issue of the journal Nature. Rokhsar, who heads OIST's Molecular Genetics Unit as a visiting professor, and Nori Satoh, head of OIST's Marine Genomics Unit, led the project.
Gills a pre-Cambrian innovation
Gerhart has been studying acorn worms for 15 years, specifically an Atlantic species, Saccoglossus kowalevskii, tracking the genes responsible for the development from egg to adult. Ten years ago, he first proposed sequencing its genome.
"I'm interested in the origins of chordates, which, of course, came from non-chordates, and hemichordates like the acorn worm are the closest we have to this lineage," he said. "So it's important to compare the development and genomes of our group, the chordates, with the hemichordates if you want to know what characteristics the common ancestor really had."
It's a small field. Only a handful of labs around the world study acorn worms, which are hard to raise in tanks. They've been largely ignored since biologists first described them in the 1800s, Gerhart said. Several co-authors of the paper lead such labs: Chris Lowe of the Hopkins Marine Station, a former postdoctoral fellow with Gerhart, Marc Kirschner of Harvard University and Nori Satoh in Japan.
One of the peculiarities of the acorn worm is its dozens of pharyngeal slits, which allow it to filter seawater pumped through them to capture nutrients, algae and bacterial prey. These slits evolved into the gill slits of fish and other marine vertebrates, which became specialized to extract oxygen from water and, in the process, lost their ancient filter feeding role.
Gerhart, who has come to appreciate the biology of the worm, said that the unique finger-like 'head' or proboscis of the acorn worm is used to probe the sand for mostly single-celled algae and bacteria, which it then re-suspends in the water to be sucked in and filtered through the gill slits.
"What's so great about having gill slits is the large volumes of water you can put through the animal to collect food; they allow high-throughput filtering and feeding, whereas other animals take one gulp, deal with the food in that one gulp, expel the water out the mouth and take another gulp," he said. "The pharyngeal area of these worms and of all deuterostomes is their most significant shared innovation."
Deuterostomes, which arose in the pre-Cambrian era, comprise chordates, acorn worms -- the most ancient deuterostome -- and a close relative, the echinoderms, which include starfish and sea urchins. Deuterostomes and another group, the protostomes -- 25 phyla encompassing the insects, mollusks and annelids like earthworms -- include all bilaterally symmetric animals.
Gene clusters for pharynx
While scientists at Baylor assembled an initial draft sequence of the Saccoglossus genome, Rokhsar teamed up with the Okinawa group to improve the genome sequence and also sequence the whole genome of a tropical Pacific species, Ptychodera flava. The two are distant cousins, separated by 370 million years of evolution.
By comparing the new genome sequences with sequences of many other animals, the team found that clusters of genes on the same chromosome in humans are often found clustered together on the acorn worm genome. Sometimes even the local structure of the cluster is the same, despite the fact that the two genomes diverged more than half a billion years ago, Rokhsar said.
A particularly interesting cluster is a group of six ordered genes that are all implicated in the development of the pharynx and gill slits in both acorn worms and vertebrates. Pharyngeal gill slits -- found at least primitively in all deuterostomes -- are thought to be an evolutionary innovation that defines the group as a whole, he said.
"We think this is an ancient deuterostome-specific cluster of genes that is involved in patterning the pharynx," Rokhsar said.
Another surprise was that deuterostomes have more than 30 genes that have no counterpart in non-deuterostomes but are similar to genes found in marine algae and bacteria. Several of these genes are involved in modifying the sugars that coat our cells. Either these are very ancient genes that all other animals lost, or they were acquired by "horizontal transfer" from algae and bacteria very early in deuterostome evolution. While bacteria are well known to exchange genes in this manner, it is rare and somewhat controversial to find bacterial-to-animal transfers, Rokhsar said.
"I hope these new sequences will encourage more people to study acorn worms," Gerhart said.
RELEASE: Magic tricks work because they take advantage of the brain's sensory assumptions, tricking audiences into seeing phantoms or overlooking sleights of hand. Now a team of UC San Francisco researchers has discovered that even brainless single-celled yeast have sensory biases that can be hacked by a carefully engineered illusion, a finding that could be used to develop new approaches to fighting diseases such as cancer.
"The ability to perceive and respond to the environment is a basic attribute of all living organisms, from the greatest to the smallest," said Wendell Lim, PhD, the study's senior author. "And so is the susceptibility to misperception. It doesn't matter if the illusion is based on molecular sensors within a single cell or neurons in the brain."
In the new study, published online Nov. 19, 2015 in Science Express, Lim and his team discovered that yeast cells falsely perceive a specifically timed pattern of stress -- caused by alternating between low and mildly increased sodium levels -- as a massive, continuously increasing ramp of stress. In response, the microbes end up over-responding and killing themselves. The results, Lim says, suggest a whole new way of looking at the perceptual abilities of simple cells and could even be used to develop new approaches to fighting diseases using the power of illusion.
Timing of stress response is yeast cells' 'Achilles heel'
"This discovery was a bit of an accident actually," said Lim, chair of the Department of Cellular and Molecular Pharmacology at UCSF, director of the UCSF Center for Systems and Synthetic Biology, and a Howard Hughes Medical Institute (HHMI) investigator. "We were interested in the general issue of how cells interpret information over time. Frequency is a key aspect of all our communications, whether it's hearing language or transmitting radio signals, but do cells themselves use this kind of information? It's something we don't know much about."
To explore this question, two postdoctoral fellows in Lim's lab, Ping Wei, PhD, now at Peking University School of Life Sciences, and Amir Mitchell, PhD, set up a system that allowed them to expose yeast to a mild stressor -- a small increase in salt in the yeast's environment -- and to oscillate between the increased salt level and the baseline level at different frequencies.
Normally, sensor molecules in a yeast cell detect changes in salt concentration and instruct the cell to respond by producing a protective chemical. After this transient response, the cell can resume growing happily as if conditions had not changed. The researchers found that the cells were perfectly capable of adapting when they flipped the salt stress on and off every minute or every 32 minutes. But to their surprise, when they tried an eight-minute oscillation of precisely the same salt level the cells quickly stopped growing and began to die off.
"That was just a jaw-dropping moment," said Mitchell. "These cells should be able to handle this level of osmotic stress, but at one particular frequency they just go haywire. We'd never seen anything like this before."
Could sensory illusions be used to fight cancer?
Mitchell, who was first author on the new study, went on to inspect the cellular mechanism underlying this unexpected, frequency-dependent toxicity. Using mathematical modeling and experiments in which he tweaked the molecular wiring of the mitogen activated protein kinase (MAPK) pathway that mediates the cells' salt-sensing system, he revealed a sensory misperception: Because of the way the MAPK pathway is set up, the cells interpret an eight-minute oscillation as an ever-increasing staircase of salt concentration. This leads to excessive activation of the cells' protective response, and ultimately to their death (see Movie).
"Why would these cells have evolved this bizarre sensitivity to salt oscillations?" Mitchell asked. "Well, we don't think that they did. It's just a side effect of the fact that the molecular signaling network yeast cells use to mediate this stress response was optimized for their natural environment, in which salt stress normally occurs in a gradually increasing ramp -- like if the yeast is sitting on a grape as morning dew slowly evaporates. It's this assumption on the part of the yeast -- their anticipation that the stress will keep getting more severe -- that creates their Achilles heel."
The study suggests that many cell types, including human cells, may be predisposed to misperceptions and could be fooled by carefully engineered illusions. For instance, Mitchell said, the signaling pathway by which human cancer cells respond to chemical growth factors is closely related to the stress-sensing MAPK pathway in yeast. Thus, identification of cell-specific misperceptions might ultimately be exploited to induce cancer cells to kill themselves, he suggested, while minimally harming healthy, neighboring cells.
"On its own, this is a humble finding," Lim said, but he believes it has broader implications for biomedical research. "Like us, cells have biased perceptions based on what environmental patterns they've evolved with. By understanding these biases, we can modulate their behavior," he said. "In particular, it's striking to realize how important the time domain is for cells. The temporal pattern with which we present any stimulus, whether it's salt concentrations, drugs or beams of light, may make all the difference."
Our closest wormy cousins: About 70% of our genes trace their ancestry back to the acorn worm
RELEASE: A team from the Okinawa Institute of Science and Technology Graduate University (OIST) and its collaborators has sequenced the genomes of two species of small water creatures called acorn worms and showed that we share more genes with them than we do with many other animals, establishing them as our distant cousins.
The study found that 8,600 families of genes are shared across deuterostomes, a large animal grouping that includes a variety of organisms, ranging from acorn worms to star fishes, from frogs to dogs, to humans. This means that approximately 70% of our genes trace their ancestry back to the original deuterostome. By comparing the genomes of acorn worms to other animals, OIST scientists inferred the presence of these genes in the common ancestor of all deuterostomes, an extinct animal that lived half a billion years ago. This research shows that the pharyngeal gene cluster is unique to the deuterostomes and it could be linked to the development of the pharynx, the region that links the mouth and nose to the esophagus in humans. These findings were published in Nature, summarizing an international collaboration between OIST researchers and teams from the US, UK, Japan, Taiwan and Canada.
Around 550 million years ago, a great variety of animals burst onto the world in an event known as the Cambrian explosion. This evolutionary radiation revealed several new animal body plans, and changed life on Earth forever, as complex animals with specialized guts and behavioural features emerged. Thanks to the genome sequencing of multiple contemporary animals of the deuterostome group, we can go back in time to unveil aspects of the long-lost ancestor of this diverse group of animals.
Acorn worms are marine creatures that live on the ocean floor and feed by filtering a steady flow of sea water through slits in the region of their gut between mouth and esophagus. These slits are distantly related to the gills of fish, and represent a critical innovation in evolution not shared with animals like flies or earthworms. Since acorn worms occupy such a critical evolutionary position relative to humans the researchers sequenced two distantly related acorn worm species, Ptychodera flava, collected in Hawaii, and Saccoglossus kowalevskii, from the Atlantic Ocean. "Their genomes are necessary to fill the gap in our understanding of the genes shared by the common ancestor of all deuterostomes," explains Dr Oleg Simakov, lead author of this study.
Indeed, beyond sequencing these two organisms, the team was also interested in identifying ancient gene families that were already present in the deuterostome ancestor. The team compared the genomes of the two acorn worms with the genomes of 32 diverse animals and found that about 8,600 families of genes are homologous, that is, evolutionarily-related, across all deuterostomes and so are confidently inferred to have been present also in the genome of their deuterostome ancestor. Human arms, birds' wings, cats' paws and the whales' flippers are classical examples of homology, because they all derive from the limbs of a common ancestor. As with anatomical structures, genes homology is defined in terms of shared ancestry. Because of later gene duplications and other processes, these 8,600 homologous genes correspond to at least 14,000 genes, or approximately 70%, of the current human genome.
The study also identified clusters of genes that are close together in acorn worm genomes and in the genomes of humans and other vertebrates. The ancient proximity of these gene clusters, preserved over half a billion years, suggests that the genes may function as a unit. One gene cluster connected with the development of the pharynx in vertebrates and acorn worms is particularly interesting. It is shared by all deuterostomes, but not present in non-deuterostome animals such as insects, octopuses, earthworms and flatworms. The pharynx of acorn worms and other animals functions to filter food and to guide it to the digestive system. In humans, this cluster is active in the formation of the thyroid glands and the pharynx. Scientists suggest there is a connection between the function of the modern thyroid and the filter feeding mechanism of acorn worms. This pharyngeal gene cluster contains six genes ordered in a common pattern in all deuterostomes and includes the genes for four proteins that are critical transcriptional regulators that control activation of numerous other genes. Genes ordered in the same way and located next to each other in the chromosomal DNA are linked and transferred together from one generation to the next. Interestingly, not only the DNA that codes for these transcription factor genes is shared among the deuterostomes, but also some of the DNA pieces that are used as binding sites for the transcription factors are conserved among these animals.
"Our analysis of the acorn worm genomes provides a glimpse into our Cambrian ancestors' complexity and supplies support for the ancient link between the pharyngeal development and the filter feeding life style that ultimately contributed to our evolution," explains Dr Simakov.
Acorn worm genome reveals gill origins of human pharynx: Earliest animals with gill slits tell biologists about origin of swallowing, speaking
RELEASE: The newly sequenced genomes of two marine worms are shedding light on the 570 million-year evolution of gills into the pharynx that today gives humans the ability to bite, chew, swallow and speak.
The draft genome sequences of two species of acorn worm, which live in U-shaped burrows in shallow, brackish water, are the first genomes of hemichordates, which retain similarities to the first animals to evolve pharyngeal or "gill" slits. Those ancestors eventually gave rise to chordates: animals with backbones and hollow nerve cords, like humans and other vertebrates.
Since acorn worms and the human lineage diverged 570 million years ago, pharyngeal slits for filtering food evolved into gills for extracting oxygen, and later into today's human upper and lower jaw and pharynx, which encompasses the thyroid gland, tongue, larynx (voice box) and various glands and muscles between the mouth and the throat. Humans and other terrestrial vertebrates actually initiate vestigial gills while embryos, though they disappear quickly and rarely persist in infants.
"The presence of these slits in acorn worms and vertebrates tells us that our last common ancestor also had them, and was likely a filter feeder like acorn worms today," said Daniel Rokhsar, one of the leaders of the sequencing effort and a UC Berkeley professor of molecular and cell biology and of physics. "Acorn worms are marine invertebrates that, despite their decidedly non-vertebrate form, are nevertheless among our closest invertebrate relatives."
"It's an ugly beast," acknowledged John Gerhart, senior author of the report and a professor of the graduate school at UC Berkeley. "Acorn worms look very different from chordates, which makes it especially surprising that they and chordates, like humans, are so similar on the genomic, developmental and cell biological levels."
In fact, about 70 percent of human genes have counterparts in the acorn worms, suggesting that these are ancient genes inherited from the common ancestor.
The research group included scientists from UC Berkeley; the Okinawa Institute of Science and Technology Graduate University in Onna, Okinawa, Japan; Stanford University's Hopkins Marine Station; the Baylor College of Medicine in Texas and the United Kingdom. They published their findings in the Nov. 19 issue of the journal Nature. Rokhsar, who heads OIST's Molecular Genetics Unit as a visiting professor, and Nori Satoh, head of OIST's Marine Genomics Unit, led the project.
Gills a pre-Cambrian innovation
Gerhart has been studying acorn worms for 15 years, specifically an Atlantic species, Saccoglossus kowalevskii, tracking the genes responsible for the development from egg to adult. Ten years ago, he first proposed sequencing its genome.
"I'm interested in the origins of chordates, which, of course, came from non-chordates, and hemichordates like the acorn worm are the closest we have to this lineage," he said. "So it's important to compare the development and genomes of our group, the chordates, with the hemichordates if you want to know what characteristics the common ancestor really had."
It's a small field. Only a handful of labs around the world study acorn worms, which are hard to raise in tanks. They've been largely ignored since biologists first described them in the 1800s, Gerhart said. Several co-authors of the paper lead such labs: Chris Lowe of the Hopkins Marine Station, a former postdoctoral fellow with Gerhart, Marc Kirschner of Harvard University and Nori Satoh in Japan.
One of the peculiarities of the acorn worm is its dozens of pharyngeal slits, which allow it to filter seawater pumped through them to capture nutrients, algae and bacterial prey. These slits evolved into the gill slits of fish and other marine vertebrates, which became specialized to extract oxygen from water and, in the process, lost their ancient filter feeding role.
Gerhart, who has come to appreciate the biology of the worm, said that the unique finger-like 'head' or proboscis of the acorn worm is used to probe the sand for mostly single-celled algae and bacteria, which it then re-suspends in the water to be sucked in and filtered through the gill slits.
"What's so great about having gill slits is the large volumes of water you can put through the animal to collect food; they allow high-throughput filtering and feeding, whereas other animals take one gulp, deal with the food in that one gulp, expel the water out the mouth and take another gulp," he said. "The pharyngeal area of these worms and of all deuterostomes is their most significant shared innovation."
Deuterostomes, which arose in the pre-Cambrian era, comprise chordates, acorn worms -- the most ancient deuterostome -- and a close relative, the echinoderms, which include starfish and sea urchins. Deuterostomes and another group, the protostomes -- 25 phyla encompassing the insects, mollusks and annelids like earthworms -- include all bilaterally symmetric animals.
Gene clusters for pharynx
While scientists at Baylor assembled an initial draft sequence of the Saccoglossus genome, Rokhsar teamed up with the Okinawa group to improve the genome sequence and also sequence the whole genome of a tropical Pacific species, Ptychodera flava. The two are distant cousins, separated by 370 million years of evolution.
By comparing the new genome sequences with sequences of many other animals, the team found that clusters of genes on the same chromosome in humans are often found clustered together on the acorn worm genome. Sometimes even the local structure of the cluster is the same, despite the fact that the two genomes diverged more than half a billion years ago, Rokhsar said.
A particularly interesting cluster is a group of six ordered genes that are all implicated in the development of the pharynx and gill slits in both acorn worms and vertebrates. Pharyngeal gill slits -- found at least primitively in all deuterostomes -- are thought to be an evolutionary innovation that defines the group as a whole, he said.
"We think this is an ancient deuterostome-specific cluster of genes that is involved in patterning the pharynx," Rokhsar said.
Another surprise was that deuterostomes have more than 30 genes that have no counterpart in non-deuterostomes but are similar to genes found in marine algae and bacteria. Several of these genes are involved in modifying the sugars that coat our cells. Either these are very ancient genes that all other animals lost, or they were acquired by "horizontal transfer" from algae and bacteria very early in deuterostome evolution. While bacteria are well known to exchange genes in this manner, it is rare and somewhat controversial to find bacterial-to-animal transfers, Rokhsar said.
"I hope these new sequences will encourage more people to study acorn worms," Gerhart said.
