Finding: A new study shows that common, complex diseases are more likely to be due to genetic variation in regions that control activity of genes, rather than in the regions that specify the protein code.
Where are the regions?
This result comes from a study of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project. The authors looked at 2.2 million DNA sequence variants (SNPs) to determine which affected gene activity. They found that activity of more than 1300 genes was affected by DNA sequence changes in regions predicted to be involved in regulating gene activity, which often lie close to, but outside, the protein-coding regions.
The challenge of large-scale studies that link a DNA variant to a disease
We predict that variants in regulatory regions make a greater contribution to complex disease than do variants that affect protein sequence. This is the first study on this scale and these results are confirming our intuition about the nature of natural variation in complex traits.
One of the challenges of large-scale studies that link a DNA variant to a disease is to determine how the variant causes the disease: our analysis will help to develop that understanding, a vital step on the path from genetics to improvements in healthcare.
What the HapMap does
Past studies of rare, monogenic disease, such as cystic fibrosis and sickle-cell anaemia, have focused on changes to the protein-coding regions of genes because they have been visible to the tools of human genetics. With the HapMap and large-scale research methods, researchers can inspect the role of regions that regulate activity of many thousands of genes.
The HapMap Project established cell cultures from participants from four populations as well as, for some samples, information from families, which can help to understand inheritance of genetic variation. The team used these resources to study gene activity in the cell cultures and tie that to DNA sequence variation
Scientists found strong evidence that SNP variation close to genes - where most regulatory regions lie - could have a dramatic effect on gene activity. Although many effects were shared among all four HapMap populations, they also shown that a significant number were restricted to one population.
What about the house keeping genes?
They also showed that genes required for the basic functions of the cell - so-called housekeeping genes - were less likely to be subject to genetic variation. This was exactly as one would expect: you can't mess too much with the fundamental life processes and we predicted we would find reduced effects on these genes.
The study also detected SNP variants that affect the activity of genes located a great distance away. Genetic regulation in the human genome is complex and highly variable: a tool to detect such distant effects will expand the search for causative variants. The authors note, however, that the small sample size of 270 HapMap individuals is sensitive enough to detect only the strongest effects.
Friday, June 20, 2008
Tuesday, June 17, 2008
Happenstance mutations matter
Scientists show that happenstance mutations matter
Finding: In experiments on bacteria grown in the lab, scientists found that evolving a new trait sometimes depended on previous, happenstance mutations. Without those earlier random mutations, the window of opportunity for the novel trait would never have opened. History might have been different.
Evolutionist Stephen Jay Gould once suggested that the if the evolution of life were “wound back” and played again from the start, it could have turned out very differently.
Though not firmly conclusive, the new research adds a real-world case study of evolution in action to the decades-old debate stirred by Gould’s thought experiment. British paleontologist Simon Conway Morris and others argued that only a few optimal solutions exist for an organism to adapt to its environment, so even if the clock were wound back, environmental pressures would eventually steer evolution toward one of those solutions — regardless of the randomness along the way.
What the scientists did
Scientists obviously can’t turn back the hands of time, but Richard Lenski and his colleagues at Michigan State University in East Lansing did the next best thing. Lenski’s team watched 12 colonies of identical E. coli bacteria evolve under carefully controlled lab conditions for 20 years, which equates to more than 40,000 generations of bacteria. After every 500 generations, the researchers froze samples of bacteria. Those bacteria could later be thawed out to “replay” the evolutionary clock from that point in time.
The evolution of a nutrient absorption ability
After about 31,500 generations, one colony of bacteria evolved the novel ability to use a nutrient that E. coli normally can’t absorb from its environment. Thawed-out samples from after the 20,000-generation mark were much more likely to re-evolve this trait than earlier samples, which suggests that an unnoticed mutation that occurred around the 20,000th generation enabled the microbes to later evolve the nutrient-absorption ability through a second mutation, the researchers report in the Proceedings of the National Academy of Sciences.
By way of contrast with another control group
In the 11 other colonies, this earlier mutation didn’t occur, so the evolution of this novel ability never happened.
Put populations in the same environment and see what happens
This is a direct empirical demonstration of Gould-like contingency in evolution. You can’t do an exact replay in nature, but scientists were able to literally put all these populations in virtually identical environments and show that contingency is really what had occurred.
What was the mutation that occured?
The next step will be to determine what that earlier mutation was and how it made the later change possible. If the first mutation didn’t offer any survival advantage to the microbes on its own, it would make the case airtight that Gould was right. That’s because a mutation that doesn’t improve an organism’s ability to survive and reproduce can’t be favored by evolution, so whether the microbe happens to have that necessary mutation when the second evolutionary change occurs becomes purely a matter of chance. Thus the first mutation must have improved the chance of the organisms survival.
The first mutation gave the microbes a survival advantage. The growth rate and the density of bacteria in the colony jumped up after the second mutation, but not after the first one. The first mutation may have set the stage for what was to come, the second mutation took advantage of the change.
Finding: In experiments on bacteria grown in the lab, scientists found that evolving a new trait sometimes depended on previous, happenstance mutations. Without those earlier random mutations, the window of opportunity for the novel trait would never have opened. History might have been different.
Evolutionist Stephen Jay Gould once suggested that the if the evolution of life were “wound back” and played again from the start, it could have turned out very differently.
Though not firmly conclusive, the new research adds a real-world case study of evolution in action to the decades-old debate stirred by Gould’s thought experiment. British paleontologist Simon Conway Morris and others argued that only a few optimal solutions exist for an organism to adapt to its environment, so even if the clock were wound back, environmental pressures would eventually steer evolution toward one of those solutions — regardless of the randomness along the way.
What the scientists did
Scientists obviously can’t turn back the hands of time, but Richard Lenski and his colleagues at Michigan State University in East Lansing did the next best thing. Lenski’s team watched 12 colonies of identical E. coli bacteria evolve under carefully controlled lab conditions for 20 years, which equates to more than 40,000 generations of bacteria. After every 500 generations, the researchers froze samples of bacteria. Those bacteria could later be thawed out to “replay” the evolutionary clock from that point in time.
The evolution of a nutrient absorption ability
After about 31,500 generations, one colony of bacteria evolved the novel ability to use a nutrient that E. coli normally can’t absorb from its environment. Thawed-out samples from after the 20,000-generation mark were much more likely to re-evolve this trait than earlier samples, which suggests that an unnoticed mutation that occurred around the 20,000th generation enabled the microbes to later evolve the nutrient-absorption ability through a second mutation, the researchers report in the Proceedings of the National Academy of Sciences.
By way of contrast with another control group
In the 11 other colonies, this earlier mutation didn’t occur, so the evolution of this novel ability never happened.
Put populations in the same environment and see what happens
This is a direct empirical demonstration of Gould-like contingency in evolution. You can’t do an exact replay in nature, but scientists were able to literally put all these populations in virtually identical environments and show that contingency is really what had occurred.
What was the mutation that occured?
The next step will be to determine what that earlier mutation was and how it made the later change possible. If the first mutation didn’t offer any survival advantage to the microbes on its own, it would make the case airtight that Gould was right. That’s because a mutation that doesn’t improve an organism’s ability to survive and reproduce can’t be favored by evolution, so whether the microbe happens to have that necessary mutation when the second evolutionary change occurs becomes purely a matter of chance. Thus the first mutation must have improved the chance of the organisms survival.
The first mutation gave the microbes a survival advantage. The growth rate and the density of bacteria in the colony jumped up after the second mutation, but not after the first one. The first mutation may have set the stage for what was to come, the second mutation took advantage of the change.
Monday, May 26, 2008
BAC: Super-Sized Inserts
Bacterial Artificial Chromosomes (BAC) have been developed to hold much larger pieces of DNA than a plasmid can. BAC vectors were originally created from part of an unusual plasmid present in some bacteria called the F’ plasmid.
The F’ plasmid allows bacteria to have “sex” (well, sort of: F’ helps bacteria give its genome to another bacteria but this only happens rarely when bacteria are under a lot of stress). F’ had been studied extensively and it was found that it could hold up to a million basepairs of DNA from another bacteria. Also, F’ has origins of replication and bacteria have a way to control how F’ is copied.
The F’ plasmid allows bacteria to have “sex” (well, sort of: F’ helps bacteria give its genome to another bacteria but this only happens rarely when bacteria are under a lot of stress). F’ had been studied extensively and it was found that it could hold up to a million basepairs of DNA from another bacteria. Also, F’ has origins of replication and bacteria have a way to control how F’ is copied.
Friday, May 16, 2008
Mitochondrial Eve
'Mitochondrial Eve' Research: Humanity Was Genetically Divided For 100,000 Years
A Picture of the Ancient Past
Finding:
Based on Anthroopological genetic research, researchers believe that about 60,000 years ago, modern humans started the journey to populate the world. However, relatively little is known about the demographic history of our species over the previous 140,000 years in Africa.
The current study focuses on Africa and refines the understanding of early modern Homo sapiens history. These early human populations were small and isolated from each other for many tens of thousands of years.
The research was based on a survey of African mitochondrial DNA (mtDNA) and is the most extensive survey of its kind. It included over 600 complete mtDNA genomes from indigenous populations across the continent.
How Old Was “Mitochondrial Eve”?
MtDNA, inherited down the maternal line, was used in 1987 to discover the age of the “Mitochondrial Eve,” the most recent common female ancestor of everyone alive today. This work has since been extended to show unequivocally that “Mitochondrial Eve” was an African woman who lived sometime during the past 200,000 years.
Recent data suggests that Eastern Africa went through a series of massive droughts between 90,000 and 135,000 years ago. It is possible that this climate shift contributed to the population splits. What is surprising is the length of time the populations were separate — for as much as half of our entire history as a species.
The study shows that tiny bands of early humans, forced apart by harsh environmental conditions, coming back from the brink to reunite and populate the world. Truly an epic drama, written in our DNA.
A Picture of the Ancient Past
Finding:
Based on Anthroopological genetic research, researchers believe that about 60,000 years ago, modern humans started the journey to populate the world. However, relatively little is known about the demographic history of our species over the previous 140,000 years in Africa.
The current study focuses on Africa and refines the understanding of early modern Homo sapiens history. These early human populations were small and isolated from each other for many tens of thousands of years.
The research was based on a survey of African mitochondrial DNA (mtDNA) and is the most extensive survey of its kind. It included over 600 complete mtDNA genomes from indigenous populations across the continent.
How Old Was “Mitochondrial Eve”?
MtDNA, inherited down the maternal line, was used in 1987 to discover the age of the “Mitochondrial Eve,” the most recent common female ancestor of everyone alive today. This work has since been extended to show unequivocally that “Mitochondrial Eve” was an African woman who lived sometime during the past 200,000 years.
Recent data suggests that Eastern Africa went through a series of massive droughts between 90,000 and 135,000 years ago. It is possible that this climate shift contributed to the population splits. What is surprising is the length of time the populations were separate — for as much as half of our entire history as a species.
The study shows that tiny bands of early humans, forced apart by harsh environmental conditions, coming back from the brink to reunite and populate the world. Truly an epic drama, written in our DNA.
Monday, April 28, 2008
Last Common Ancestor Of Neanderthals And Humans
Finding: Fossil Found In Europe, 1.2 Million Years Old
That's 500,000 years older than the previous oldest known humanlike fossils from the area. The new find bolsters the view that Homo reached Europe not long after leaving Africa almost 2 million years ago.
It seems probable that the first European population came from the region of the Near East, the true crossroads between Africa and Eurasia, and that it was related to the first demographic expansion out of Africa.
The researchers tentatively classified the new fossil as an earlier example Homo antecessor (Pioneer Man), the species represented by the previous oldest fossils and thought to be the last common ancestor of Neanderthals and modern humans.
That's 500,000 years older than the previous oldest known humanlike fossils from the area. The new find bolsters the view that Homo reached Europe not long after leaving Africa almost 2 million years ago.
It seems probable that the first European population came from the region of the Near East, the true crossroads between Africa and Eurasia, and that it was related to the first demographic expansion out of Africa.
The researchers tentatively classified the new fossil as an earlier example Homo antecessor (Pioneer Man), the species represented by the previous oldest fossils and thought to be the last common ancestor of Neanderthals and modern humans.
Sunday, April 6, 2008
Early Human Populations Evolved Separately For 100,000 Years
Finding:
A team of Genographic researchers and their collaborators have published the most extensive survey to date of African mitochondrial DNA (mtDNA). Over 600 complete mtDNA genomes from indigenous populations across the continent were analyzed by the scientists. Analyses of the extensive data provide surprising insights into the early demographic history of human populations before they moved out of Africa, illustrating that these early human populations were small and isolated from each other for many tens of thousands of years.
MtDNA, inherited down the maternal line, was used to discover the age of the famous 'mitochondrial Eve' in 1987. This work has since been extended to show unequivocally that the most recent common female ancestor of everyone alive today was an African woman who lived in the past 200,000 years. Paleontology provides corroborating evidence that our species originated on this continent approximately 200,000 years ago.
The migrations after 60,000 years ago that led modern humans on their epic journeys to populate the world have been the primary focus of anthropological genetic research, but relatively little is known about the demographic history of our species over the previous 140,000 years in Africa. The current study returns the focus to Africa and in doing so refines our understanding of early modern Homo sapiens history.
There is strong evidence of ancient population splits beginning as early as 150,000 years ago, probably giving rise to separate populations localized to Eastern and Southern Africa. It was only around 40,000 years ago that they became part of a single pan-African population, reunited after as much as 100,000 years apart.
Recent paleoclimatological data suggests that Eastern Africa went through a series of massive droughts between 135,000-90,000 years ago. It is possible that this climatological shift contributed to the population splits. What is surprising is the length of time the populations were separate - as much as half of our entire history as a species.
A team of Genographic researchers and their collaborators have published the most extensive survey to date of African mitochondrial DNA (mtDNA). Over 600 complete mtDNA genomes from indigenous populations across the continent were analyzed by the scientists. Analyses of the extensive data provide surprising insights into the early demographic history of human populations before they moved out of Africa, illustrating that these early human populations were small and isolated from each other for many tens of thousands of years.
MtDNA, inherited down the maternal line, was used to discover the age of the famous 'mitochondrial Eve' in 1987. This work has since been extended to show unequivocally that the most recent common female ancestor of everyone alive today was an African woman who lived in the past 200,000 years. Paleontology provides corroborating evidence that our species originated on this continent approximately 200,000 years ago.
The migrations after 60,000 years ago that led modern humans on their epic journeys to populate the world have been the primary focus of anthropological genetic research, but relatively little is known about the demographic history of our species over the previous 140,000 years in Africa. The current study returns the focus to Africa and in doing so refines our understanding of early modern Homo sapiens history.
There is strong evidence of ancient population splits beginning as early as 150,000 years ago, probably giving rise to separate populations localized to Eastern and Southern Africa. It was only around 40,000 years ago that they became part of a single pan-African population, reunited after as much as 100,000 years apart.
Recent paleoclimatological data suggests that Eastern Africa went through a series of massive droughts between 135,000-90,000 years ago. It is possible that this climatological shift contributed to the population splits. What is surprising is the length of time the populations were separate - as much as half of our entire history as a species.
Friday, March 14, 2008
Two Explosive Evolutionary Events Shaped Early History Of Multicellular Life
The Avalon Explosion suggests that more than one explosive evolutionary event may have taken place during the early evolution of animals. Using rigorous analytical methods, scientists have identified another explosive evolutionary event that occurred about 33 million years earlier among macroscopic life forms unrelated to the Cambrian animals.
The Cambrian explosion event refers to the sudden appearance of most animal groups in a geologically short time period between 542 and 520 million years ago, in the early Cambrian Period. Although there were not as many animal species as in modern oceans, most (if not all) living animal groups were represented in the Cambrian oceans.
Methodology
To test whether other major branches of life also evolved in an abrupt and explosive manner, Virginia Tech scientists analyzed the Ediacara fossils: the oldest complex, multicellular organisms that had lived in oceans from 575 to 542 million years ago; that is, before the Cambrian Explosion of animals. What was notable was that the Ediacara organisms do not have an ancestor-descendant relationship with the Cambrian animals, and most of them went extinct before the Cambrian Explosion.
This group of organisms -- most species -- seems to be distinct from the Cambrian animals. But how did those Ediacara organisms first evolve? Did they also appear in an explosive evolutionary event, or is the Cambrian Explosion a truly unparalleled event. 50 characters were identified and mapped the distribution of these characters in more than 200 Ediacara species. These species cover three evolutionary stages of the entire Ediacara history across 33 million years. The three successive evolutionary stages are represented by the Avalon, White Sea, and Nama assemblages (all named after localities where representative fossils of each stage can be found).
The earliest Avalon stage was represented by relatively few species. These earliest Ediacara life forms already occupied a full morphological range of body plans that would ever be realized through the entire history of Ediacara organisms. In other words, major types of Ediacara organisms appeared at the dawn of their history, during the Avalon Explosion. Then Ediacara organisms diversified in White Sea time and then declined in Nama time. But, despite this notable waxing and waning in the number of species, the morphological range of the Avalon organisms were never exceeded through the subsequent history of Ediacara.
The process involved adapting quantitative methods that had been used previously for studying morphological evolution of animals, but never applied to the enigmatic Ediacara organisms. "We think of diversity in terms of individual species. But species may be very similar in their overall body plan. For example, 50 species of fly may not differ much from one another in terms of their overall shape -- they all represent the same body plan. On the other hand, a set of just three species that include a fly, a frog and an earthworm represent much more morphological variation. We can thus think of biodiversity not only in terms of how many different species there are but also how many fundamentally distinct body plans are being represented.
The approach combined both those approaches. In addition, the method relies on converting different morphologies into numerical (binary) data. This strategy allows us to describe, more objectively and more consistently, enigmatic fossil life forms, which are preserved mostly as two-dimensional impressions and are not understood well in terms of function, ecology, or physiology.
Scientists are still unsure what were the driving forces behind the rapid morphological expansion during the Avalon explosion, and why the morphological range did not expand, shrink, or shift during the subsequent White Sea and Nama stages.
The evolution of earliest macroscopic and complex life also went through an explosive event before to the Cambrian Explosion. It now appears that at the dawn of the macroscopic life, between 575 and 520 million years ago, there was not one, but at least two major episodes of abrupt morphological expansion.
The Cambrian explosion event refers to the sudden appearance of most animal groups in a geologically short time period between 542 and 520 million years ago, in the early Cambrian Period. Although there were not as many animal species as in modern oceans, most (if not all) living animal groups were represented in the Cambrian oceans.
Methodology
To test whether other major branches of life also evolved in an abrupt and explosive manner, Virginia Tech scientists analyzed the Ediacara fossils: the oldest complex, multicellular organisms that had lived in oceans from 575 to 542 million years ago; that is, before the Cambrian Explosion of animals. What was notable was that the Ediacara organisms do not have an ancestor-descendant relationship with the Cambrian animals, and most of them went extinct before the Cambrian Explosion.
This group of organisms -- most species -- seems to be distinct from the Cambrian animals. But how did those Ediacara organisms first evolve? Did they also appear in an explosive evolutionary event, or is the Cambrian Explosion a truly unparalleled event. 50 characters were identified and mapped the distribution of these characters in more than 200 Ediacara species. These species cover three evolutionary stages of the entire Ediacara history across 33 million years. The three successive evolutionary stages are represented by the Avalon, White Sea, and Nama assemblages (all named after localities where representative fossils of each stage can be found).
The earliest Avalon stage was represented by relatively few species. These earliest Ediacara life forms already occupied a full morphological range of body plans that would ever be realized through the entire history of Ediacara organisms. In other words, major types of Ediacara organisms appeared at the dawn of their history, during the Avalon Explosion. Then Ediacara organisms diversified in White Sea time and then declined in Nama time. But, despite this notable waxing and waning in the number of species, the morphological range of the Avalon organisms were never exceeded through the subsequent history of Ediacara.
The process involved adapting quantitative methods that had been used previously for studying morphological evolution of animals, but never applied to the enigmatic Ediacara organisms. "We think of diversity in terms of individual species. But species may be very similar in their overall body plan. For example, 50 species of fly may not differ much from one another in terms of their overall shape -- they all represent the same body plan. On the other hand, a set of just three species that include a fly, a frog and an earthworm represent much more morphological variation. We can thus think of biodiversity not only in terms of how many different species there are but also how many fundamentally distinct body plans are being represented.
The approach combined both those approaches. In addition, the method relies on converting different morphologies into numerical (binary) data. This strategy allows us to describe, more objectively and more consistently, enigmatic fossil life forms, which are preserved mostly as two-dimensional impressions and are not understood well in terms of function, ecology, or physiology.
Scientists are still unsure what were the driving forces behind the rapid morphological expansion during the Avalon explosion, and why the morphological range did not expand, shrink, or shift during the subsequent White Sea and Nama stages.
The evolution of earliest macroscopic and complex life also went through an explosive event before to the Cambrian Explosion. It now appears that at the dawn of the macroscopic life, between 575 and 520 million years ago, there was not one, but at least two major episodes of abrupt morphological expansion.
Subscribe to:
Posts (Atom)