Earlier this week, over a hundred scientists, lawyers, and entrepreneurs gathered to discuss the radical possibility of creating a synthetic human genome. Strangely, journalists were not invited, and attendees were told to keep a tight lip. Which, given the weighty subject matter, is obvious cause for concern.
Genomics entrepreneur Craig Venter has created a synthetic cell that contains the smallest genome of any known, independent organism. Functioning with 473 genes, the cell is a milestone in his team’s 20-year quest to reduce life to its bare essentials and, by extension, to design life from scratch.
Discovery of unfixed endogenous retrovirus insertions in diverse human populations
Authors:
Wildshutte et al
Abstract:
Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from less than 0.0005 to greater than 0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity.
Humans have fewer remnants of viral DNA in their genes compared to other mammals, a new study has found. This decrease could be because of reduced exposure to blood-borne viruses as humans evolved to use tools rather than biting during violent conflict and the hunting of animals.
Despite natural defence systems, a retrovirus occasionally infects a mammal's egg or sperm, and the virus's genetic code gets incorporated into the animal's own genome. This viral 'fossil' then passes down from generation to generation: we all carry remnants of DNA from viruses that infected our ancestors millions of years ago. These 'endogenous retroviruses' (ERVs) appear not to cause us any harm, even though they are known to result in diseases such as cancer in other animals.
A team of researchers from the University of Oxford and Plymouth University, UK, and the Aaron Diamond AIDS Research Center, USA, wondered if there was a combination of factors unique to humans that explained why these viral fossils in our genomes remain benign. They counted the number of times that retroviruses appear to have been integrated into an animal's genome in humans, comparing humans with 39 other mammalian species, including chimpanzees, dolphins and giant pandas.
Reporting their results in the journal Retrovirology, the researchers compared the genetic signature of the two edges of the virus. These edges are identical when the virus first invades the genome, but as they acquire random mutations over time, they slowly begin to diverge. By tracking this divergence, the research team could measure how long the retrovirus had spent in an animal's genome.
Using this measure, they found that, compared to other animals, far fewer retroviruses were incorporated into the genome for humans and other apes over the last 10 million years. Even compared to animals very similar to us, humans are unusual in not having acquired any new types of retroviruses into their DNA over the last 30 million years.
In the decade since the genome was sequenced in 2003, scientists and doctors have struggled to answer an all-consuming question: Which DNA mutations cause disease?
A new computational technique developed at the University of Toronto may now be able to tell us.
A Canadian research team led by professor Brendan Frey has developed the first method for 'ranking' genetic mutations based on how living cells 'read' DNA, revealing how likely any given alteration is to cause disease. They used their method to discover unexpected genetic determinants of autism, hereditary cancers and spinal muscular atrophy, a leading genetic cause of infant mortality.
Their findings appear in today's issue of the leading journal Science.
Think of the human genome as a mysterious text, made up of three billion letters. "Over the past decade, a huge amount of effort has been invested into searching for mutations in the genome that cause disease, without a rational approach to understanding why they cause disease," says Frey, also a senior fellow at the Canadian Institute for Advanced Research. "This is because scientists didn't have the means to understand the text of the genome and how mutations in it can change the meaning of that text." Biologist Eric Lander of the Massachusetts Institute of Technology captured this puzzle in his famous quote: "Genome. Bought the book. Hard to read."
What was Frey's approach? We know that certain sections of the text, called exons, describe the proteins that are the building blocks of all living cells. What wasn't appreciated until recently is that other sections, called introns, contain instructions for how to cut and paste exons together, determining which proteins will be produced. This 'splicing' process is a crucial step in the cell's process of converting DNA into proteins, and its disruption is known to contribute to many diseases.
Most research into the genetic roots of disease has focused on mutations within exons, but increasingly scientists are finding that diseases can't be explained by these mutations. Frey's team took a completely different approach, examining changes to text that provides instructions for splicing, most of which is in introns.
Frey's team used a new technology called 'deep learning' to teach a computer system to scan a piece of DNA, read the genetic instructions that specify how to splice together sections that code for proteins, and determine which proteins will be produced.
Unlike other machine learning methods, deep learning can make sense of incredibly complex relationships, such as those found in living systems in biology and medicine. "The success of our project relied crucially on using the latest deep learning methods to analyze the most advanced experimental biology data," says Frey, whose team included members from University of Toronto's Faculty of Applied Science & Engineering, Faculty of Medicine and the Terrence Donnelly Centre for Cellular and Biomolecular Research, as well as Microsoft Research and the Cold Spring Harbor Laboratory. "My collaborators and our graduate students and postdoctoral fellows are world-leading experts in these areas."
Once they had taught their system how to read the text of the genome, Frey's team used it to search for mutations that cause splicing to go wrong. They found that their method correctly predicted 94 percent of the genetic culprits behind well-studied diseases such as spinal muscular atrophy and colorectal cancer, but more importantly, made accurate predictions for mutations that had never been seen before.
They then launched a huge effort to tackle a condition with complex genetic underpinnings: autism spectrum disorder. "With autism there are only a few dozen genes definitely known to be involved and these account for a small proportion of individuals with this condition," says Frey.
In collaboration with Dr. Stephen Scherer, senior scientist and director of The Centre for Applied Genomics at SickKids and the University of Toronto McLaughlin Centre, Frey's team compared mutations discovered in the whole genome sequences of children with autism, but not in controls. Following the traditional approach of studying protein-coding regions, they found no differences. However, when they used their deep learning system to rank mutations according to how much they change splicing, surprising patterns appeared.
"When we ranked mutations using our method, striking patterns emerged, revealing 39 novel genes having a potential role in autism susceptibility," Frey says.
New genetic research reveals that a small group of hunger-gatherers now living in Southern Africa once was so large that it comprised the majority of living humans during most of the past 150,000 years. Only during the last 22,000 years have the other African ethnicities, including the ones giving rise to Europeans and Asians, become vastly most numerous. Now the Khoisan (who sometimes call themselves Bushmen) number about 100,000 individuals, while the rest of humanity numbers 7 billion. Their lives and ways have remained unaltered for hundreds of generations, with only recent events endangering their hunter-gatherer lifestyles. The study's findings will be published in the journal Nature Communications on 4 December 2014.
By comparing nearly all the genes of these individuals -- their genomes -- with the genomes of 1,462 people from around the world, the researchers discovered that the inflow of new genes into the Khoisan peoples has been quite restricted the past 150,000 years, indicating that this large hunter-gatherer culture was physically isolated for most of its history and that its men typically did not take wives from outside the group.
"Khoisan hunter-gatherers in Southern Africa always have perceived themselves as the oldest people" said Stephan Schuster, a former Penn State University professor, now at Nanyang Technological University in Singapore and a leader of the research team, which includes scientists at Penn State and other research universities in the United States, Brazil, and Singapore. The Nature Communication paper analyzes five study participants from different tribes in Namibia. The study investigated 420,000 genetic variants across 1,462 genomes from 48 ethnic groups in populations worldwide. These analyses reveal that Southern African Khoisans are genetically distinct not only from Europeans and Asians, but also from all other Africans. The paper's first author Hie Lim Kim, formerly at Penn State and now at Nanyang Technological University, said "It is fascinating to unravel the population history of humankind over the last 150,000 years."
By conducting extensive computational analyses, the team demonstrated that two of the sequenced individuals showed no signs of having inherited any genetic material from members of other ethnic groups. Interestingly, these individuals are the oldest members of the Ju/'hoansi tribe, which still live in protected areas of Northwest Namibia. "This and previous studies show that the Khoisan peoples and the rest of modern humanity shared their most recent common ancestor approximately 150,000 years ago, so it was entirely unexpected to find that this group apparently did not intermarry with non-Khoisan neighbors for many thousand years," said Webb Miller, professor of Bioinformatics at Penn State and a member of the research team. "The current Khoisan culture and tradition, where marriage occurs either among Khoisan groups or results in female members leaving their tribes after marrying non-Khoisan men, appears to be long-standing."
The cultural and genetic persistence of the Ju/'hoansi tribe is intriguing, the researchers say, because genetic and genomic analysis of ancient hominid lineages such as the Neanderthals, as well as non-African humans, have shown that intermarrying does occur frequently in these groups and is traceable over the entire time span of 150,000 history during which anatomically modern humans have lived. "We also observed gene flow for some of the other Khoisan groups, as defined by their largely varying language, but a key finding of this study is that, even today, individuals without genes from other communities can be identified within the Ju/'hoansi population and possibly others," Schuster said.
Whole-Genome Sequencing of the World’s Oldest People
Authors:
Gierman et al
Abstract:
Supercentenarians (110 years or older) are the world’s oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.
Cats and humans have shared the same households for at least 9,000 years, but we still know very little about how our feline friends became domesticated. An analysis of the cat genome by researchers at Washington University School of Medicine in St. Louis reveals some surprising clues.
The research appears Nov. 10 in the Proceedings of the National Academy of Sciences Early Edition.
Cats have a relatively recent history of domestication compared with dogs; canines arose from wolves over 30,000 years ago.
"Cats, unlike dogs, are really only semidomesticated," said senior author Wes Warren, PhD, associate professor of genetics at The Genome Institute at Washington University. "They only recently split off from wild cats, and some even still breed with their wild relatives. So we were surprised to find DNA evidence of their domestication."
One way scientists can understand the genetics of domestication is to look at what parts of the genome are altered in response to living together with humans, Warren added.
The researchers compared the genomes of domestic cats and wild cats, finding specific regions of the domestic cat genome that differed significantly.
The scientists found changes in the domestic cat's genes that other studies have shown are involved in behaviors such as memory, fear and reward-seeking. These types of behaviors -- particularly those when an animal seeks a reward -- generally are thought to be important in the domestication process.
"Humans most likely welcomed cats because they controlled rodents that consumed their grain harvests," said Warren. "We hypothesized that humans would offer cats food as a reward to stick around."
This meant that certain cats that would normally prefer to lead solitary lives in the wild had an additional incentive to stay with humans. Over time, humans preferred to keep cats that were more docile.
Transfer RNAs (tRNAs) are ancient workhorse molecules and part of the cellular process that creates the proteins, critical building blocks of life that keep a cell running smoothly. A new discovery suggests that the number of human genomic loci that might be coding for tRNAs is nearly double what is currently known. Most of the newly identified loci resemble the sequences of mitochondrial tRNAs suggesting unexpected new links between the human nuclear and mitochondrial genomes, links that are not currently understood.
Transfer RNAs (tRNAs) represent an integral component of the translation of a messenger RNA (mRNA) into an amino acid sequence. TRNAs are non-coding RNA molecules and can be found in all three kingdoms of life i.e., in archaea, bacteria and eukaryotes.
At the DNA level, a triplet of consecutive nucleotides known as the "codon" is used to encode an amino acid. Frequently, a given amino acid can be encoded by more than one codon: in fact, there are 61 distinct codons encoding the 20 standard human amino acids. During translation, each of the codons contained in the coding region of the mRNA at hand is recognized by its matching tRNA and the corresponding amino acid added to the nascent amino acid sequence. It has been known for many years that each of these 61 tRNAs has multiple copies spread throughout the genome that is found in the human nucleus. The presence of multiple genomic loci from which the same molecule can be made is a fairly standard trick of genomic organization: processing these loci in parallel can ensure that adequate amounts of each tRNA can be generated quickly enough to meet the high demand that the amino acid translation process imposes on the cell. In addition to the 61 tRNAs that are found in the human nuclear genome, 22 more tRNAs are encoded in the genome of the cellular organelle known as the mitochondrion: the mitochondrion, originally a bacterium itself, uses these 22 tRNAs to make proteins out of the just-over-a-dozen mRNAs that are encoded in its genome.
Recent research efforts have shown that tRNAs can have other roles, which go beyond their involvement in protein synthesis. For example, tRNAs can affect the physiology of a cell, they can modulate the abundance of important molecules, etc. These and other unexpected findings have revived interest in looking at tRNAs, this time under a different prism. But, how many tRNAs are actually encoded by the human genome and could be potentially involved in amino acid translation and other processes?
A team led by Isidore Rigoutsos, Director of the Computational Medicine Center at Thomas Jefferson University (TJU), set out to tackle this question and they have reported their findings in a study that was just published in the journal Frontiers in Genetics. "What we found, frankly, surprised us," said Rigoutsos.
The team searched the 3 billion base pairs of the human genome for DNA sequences that resembled the 530 known nuclear and mitochondrial tRNAs. Even though they used very stringent criteria in their searches, they found 454 "lookalike" loci, i.e., sequences that look like tRNA, but haven't yet been experimentally confirmed as such. The researchers found nearly as many as the known ones with which they started: 81% of these tRNA-lookalikes had not been reported previously. Rather unexpectedly, the team found that most of these new loci resembled some of the 22 mitochondrial tRNAs.
Interestingly, the discovered tRNA lookalikes are not spread uniformly across the 24 chromosomes. Instead, they have penetrated preferentially some chromosomes and have avoided others. For example, chromosomes 1, 2, 7, 8 and 9 claim the lion's share of the discovered tRNA-lookalikes. On the other hand, chromosome 18 contains no lookalikes. Also, some of the codons are particularly over-represented among the lookalikes whereas other codons are absent.
The surprises did not stop there. The team also discovered that in the chromosomes where the tRNA-lookalikes are found their locations are not accidental either. Instead, the lookalikes are positioned in close proximity to known nuclear tRNAs. This of course begs the question whether the tRNA-lookalikes are transcribed, just like the known tRNAs. By examining public repositories, the team found evidence of transcription for more than 20% of the discovered tRNA-lookalikes: the transcriptional profiles appear to depend on cell type, which suggests that more of the look-alikes will be found to be transcribed as data from more cell types become available. On several occasions, the public data revealed evidence for molecules whose endpoints matched exactly the endpoints of the tRNA-lookalikes discovered by the team. "This is certainly exciting, but it is currently unclear whether these molecules participate in translation as tRNAs, or have entirely different roles," said Rigoutsos.
The largest genome-wide association study (GWAS) to date, involving more than 300 institutions and more than 250,000 subjects, roughly doubles the number of known gene regions influencing height to more than 400. The study, from the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium, provides a better glimpse at the biology of height and offers a model for investigating traits and diseases caused by many common gene changes acting together. Findings were published online October 5 by Nature Genetics.
"Height is almost completely determined by genetics, but our earlier studies were only able to explain about 10 percent of this genetic influence," says Joel Hirschhorn, MD, PhD, of Boston Children's Hospital and the Broad Institute of MIT and Harvard, leader of the GIANT Consortium and co-senior investigator on the study. "Now, by doubling the number of people in our study, we have a much more complete picture of how common genetic variants affect height—how many of them there are and how much they contribute."
The GIANT investigators, numbering in the hundreds, shared and analyzed data from the genomes of 253,288 people. They checked about two million common genetic variants (those that showed up in at least 5 percent of their subjects). From this pool, they pinned down 697 (in 424 gene regions) as being related to height, the largest number to date associated with any trait or disease.
"We can now explain about 20 percent of the heritability of height, up from about 12 percent where we were before," says co-first author Tonu Esko, PhD, of Boston Children's Hospital, the Broad Institute and the University of Tartu (Estonia).
"The study also narrows down the genomic regions that contain a substantial proportion of remaining variation—to be discovered with even larger sample sizes," adds co-senior investigator Peter Visscher, PhD, of the University of Queensland, Australia.
New findings by scientists at the University of California, Santa Cruz, suggest that an evolutionary arms race between rival elements within the genomes of primates drove the evolution of complex regulatory networks that orchestrate the activity of genes in every cell of our bodies.
The arms race is between mobile DNA sequences known as "retrotransposons" (a.k.a. "jumping genes") and the genes that have evolved to control them. The UC Santa Cruz researchers have, for the first time, identified genes in humans that make repressor proteins to shut down specific jumping genes. The researchers also traced the rapid evolution of the repressor genes in the primate lineage.
Their findings, published September 28 in Nature, show that over evolutionary time, primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. Furthermore, their findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome.
"We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about," said Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study.
Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease. Often the effect is neutral, simply adding to the overall size of the genome. Very rarely the effect might be advantageous, because the added DNA can itself be a source of new regulatory elements that enhance gene expression. But the high probability of deleterious effects means natural selection favors the evolution of mechanisms to prevent jumping events.
Scientists estimate that jumping genes or "transposable elements" account for at least 50 percent of the human genome, and retrotransposons are by far the most common type.
"There have been successive waves of retrotransposon activity in primate evolution, when a transposable element changed to become expressed and replicated itself throughout the genome until something turned it off," Salama said. "We've discovered a major mechanism by which the genome is able to shut down these mobile DNA elements."
The repressors identified in the new study belong to a large family of proteins known as "KRAB zinc finger proteins." These are DNA-binding proteins that repress gene activity, and they constitute the largest family of gene-regulating proteins in mammals. The human genome has over 400 genes for KRAB zinc finger proteins, and about 170 of them have emerged since primates diverged from other mammals.
According to Salama, her team's findings support the idea that expansion of this family of repressor genes occurred in response to waves of retrotransposon activity. Because repression of a jumping gene also affects genes located near it on the chromosome, the researchers suspect that these repressors have been co-opted for other gene-regulatory functions, and that those other functions have persisted and evolved long after the jumping genes the repressors originally turned off have degraded due to the accumulation of random mutations.
"The way this type of repressor works, part of it binds to a specific DNA sequence and part of it binds other proteins to recruit a whole complex of proteins that creates a repressive landscape in the genome. This affects other nearby genes, so now you have a potential new layer of regulation available for further evolution," Salama said.
They lived in America about 13,000 years ago where they hunted mammoth, mastodons and giant bison with big spears. The Clovis people were not the first humans in America, but they represent the first humans with a wide expansion on the North American continent – until the culture mysteriously disappeared only a few hundred years after its origin. Who the Clovis people were and which present day humans they are related to has been discussed intensely and the issue has a key role in the discussion about how the Americas were peopled. Today there exists only one human skeleton found in association with Clovis tools and at the same time it is among the oldest human skeletons in the Americas. It is a small boy between 1 and 1.5 years of age – found in a 12,600 old burial site, called the Anzick Site, in Wilsall, Montana, USA. Now an international team headed by Danish researcher Eske Willerslev has mapped his genome thereby reviving the scientific debate about the colonization of the Americas.
Roughly estimated some 80 % of all present-day Native American populations on the two American continents are direct descendants of the Clovis boy's family. The remaining 20 % are more closely related with the Clovis family than any other people on Earth, says Lundbeck Professor Eske Willerslev from the Centre for GeoGenetics at the Natural History Museum of Denmark, University of Copenhagen. This surprising result has now been published in the scientific journal Nature. The discovery is so decisive that Nature has chosen to send the article to the press at a later time than usual as they fear the media embargo may be broken. A comprehensive international telephone press conference has been arranged and will be held in the Crow tribe's reservation in Montana – close to where the boy was found. Behind the results are a group of international researchers led by Professor Eske Willerslev from Centre of Excellence in GeoGenetics, Natural History Museum at University of Copenhagen, Denmark.
Genome-wide evidence of Austronesian–Bantu admixture and cultural reversion in a hunter-gatherer group of Madagascar
Authors:
Pierron et al
Abstract:
Linguistic and cultural evidence suggest that Madagascar was the final point of two major dispersals of Austronesian- and Bantu-speaking populations. Today, the Mikea are described as the last-known Malagasy population reported to be still practicing a hunter-gatherer lifestyle. It is unclear, however, whether the Mikea descend from a remnant population that existed before the arrival of Austronesian and Bantu agriculturalists or whether it is only their lifestyle that separates them from the other contemporary populations of South Madagascar. To address these questions we have performed a genome-wide analysis of >700,000 SNP markers on 21 Mikea, 24 Vezo, and 24 Temoro individuals, together with 50 individuals from Bajo and Lebbo populations from Indonesia. Our analyses of these data in the context of data available from other Southeast Asian and African populations reveal that all three Malagasy populations are derived from the same admixture event involving Austronesian and Bantu sources. In contrast to the fact that most of the vocabulary of the Malagasy speakers is derived from the Barito group of the Austronesian language family, we observe that only one-third of their genetic ancestry is related to the populations of the Java-Kalimantan-Sulawesi area. Because no additional ancestry components distinctive for the Mikea were found, it is likely that they have adopted their hunter-gatherer way of life through cultural reversion, and selection signals suggest a genetic adaptation to their new lifestyle.
The newly sequenced genome of the Amborella plant addresses Darwin's "abominable mystery" -- the question of why flowers suddenly proliferated on Earth millions of years ago. The genome sequence sheds new light on a major event in the history of life on Earth: the origin of flowering plants, including all major food crop species. On 20 December 2013, a paper by the Amborella Genome Sequencing Project that includes a full description of the analyses performed by the project, as well as implications for flowering plant research, will be published in the journal Science. The paper is among three on different research areas related to the Amborella genome that will be published in the same issue of the journal.
Amborella (Amborella trichopoda) is unique as the sole survivor of an ancient evolutionary lineage that traces back to the last common ancestor of all flowering plants. The plant is a small understory tree found only on the main island of New Caledonia in the South Pacific. An effort to decipher the Amborella genome -- led by scientists at Penn State University, the University at Buffalo, the University of Florida, the University of Georgia, and the University of California-Riverside -- is uncovering evidence for the evolutionary processes that paved the way for the amazing diversity of the more than 300,000 flowering plant species we enjoy today.
This unique heritage gives Amborella a special role in the study of flowering plants. "In the same way that the genome sequence of the platypus -- a survivor of an ancient lineage -- can help us study the evolution of all mammals, the genome sequence of Amborella can help us learn about the evolution of all flowers," said Victor Albert of the University at Buffalo.
Scientists who sequenced the Amborella genome say that it provides conclusive evidence that the ancestor of all flowering plants, including Amborella, evolved following a "genome doubling event" that occurred about 200 million years ago. Some duplicated genes were lost over time but others took on new functions, including contributions to the development of floral organs.
As described in a patent recently granted by the United States Patent Office, consumer genomics company 23andMe has developed a system for helping prospective parents choose the traits of their offspring, from disease risk to hair color. Put another way, it’s a designer baby-making system.link.
The company says it does not intend to use the technology this way. “When we originally introduced the tool and filed the patent there was some thinking the feature could have applications for fertility clinics,” said Catherine Afarian, a 23andMe spokeswoman. “But we’ve never pursued the idea, and have no plans to do so.”
Filed in December 2008, the patent — number 8543339, “Gamete donor selection based on genetic calculations” — sounds like something out of Gattaca, the 1997 movie that came to symbolize tensions between self-determination and biologically ordained fate.
The patent describes a technology that would take a customer’s preferences for a child’s traits, compute the likely genomic outcomes of combinations between a customer’s sperm or egg and other people’s sex cells, and describe which potential reproductive matches would most likely produce the desired baby.
Among the traits listed in the application as examples of possible choice are: height, weight, hair color, risks of colorectal cancer and congenital heart defects, expected life span, expected lifetime health care costs, and athleticism. The company, which has about 400,000 customers, offers genomic analysis of more than 240 traits altogether, from Alzheimer’s disease risk to breast shape and memory. Additional traits from this longer list could presumably be used the same way.
The first sequenced tiger genome shows that big cats evolved to kill.
Genes for strong muscle fibers and for meat-eating appear narrowly shared, researchers reported, among species as distinct as the African lion and Asia's snow leopard.
Scientists mapped the genes of the endangered Siberian tiger (or Amur tiger), both to understand the genes that make big cat species distinct from one another and to aid efforts to preserve genetic diversity in wild tiger populations.
It is nothing short of a world record in DNA research that scientists at the Centre for GeoGenetics at the Natural History Museum of Denmark (University of Copenhagen) have hit. They have sequenced the so far oldest genome from a prehistoric creature. They have done so by sequencing and analyzing short pieces of DNA molecules preserved in bone-remnants from a horse that had been kept frozen for the last 700.000 years in the permafrost of Yukon, Canada. By tracking the genomic changes that transformed prehistoric wild horses into domestic breeds, the researchers have revealed the genetic make-up of modern horses with unprecedented details. The spectacular results are now published in the international scientific journal Nature.
DNA molecules can survive in fossils well after an organism dies. Not as whole chromosomes, but as short pieces that could be assembled back together, like a puzzle. Sometimes enough molecules survive so that the full genome sequence of extinct species could be resurrected and over the last years, the full genome sequence of a few ancient humans and archaic hominins has been characterized. But so far, none dated back to before 70,000 years.
Now Dr. Ludovic Orlando and Professor Eske Willerslev from the Centre for GeoGenetics have beaten this DNA-record by about 10 times. Thereby the two researchers – in collaboration with Danish and international colleagues – have been able to track major genomic changes over the last 700.000 years of evolution of the horse lineage.
First, by comparing the genome in the 700,000 year old horse with the genome of a 43,000 year old horse, six present day horses and the donkey the researchers could estimate how fast mutations accumulate through time and calibrate a genome-wide mutation rate. This revealed that the last common ancestor of all modern equids was living about 4.0-4.5 million years ago. Therefore, the evolutionary radiation underlying the origin of horses, donkeys and zebras reaches back in time twice as long as previously thought. Additionally, this new clock revealed multiple episodes of severe demographic fluctuation in horse history, in phase with major climatic changes such as the Last Glacial Maximum, some 20,000 years ago.
The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses
Authors:
1. Alexander Suh (a,c)
2. Jürgen Brosius (a)
3. Jürgen Schmitz (a)
4. Jan Ole Kriegs (a,b)
Affiliations:
a. Institute of Experimental Pathology (ZMBE), University of Münster, Von-Esmarch-Straße 56, D-48149 Münster, Germany
b. LWL-Museum für Naturkunde, Westfälisches Landesmuseum mit Planetarium, Sentruper Straße 285, D-48161 Münster, Germany
c. Present address: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18D, SE-752 36 Uppsala, Sweden
Abstract:
Paleovirology involves the identification of ancient endogenous viral elements within eukaryotic genomes. The evolutionary origins of the reverse-transcribing hepatitis B viruses, however, remain elusive, due to the small number of endogenized sequences present in host genomes. Here we report a comprehensively dated genomic record of hepatitis B virus endogenizations that spans bird evolution from greater than 82 to less than 12.1 million years ago. The oldest virus relic extends over a 99% complete hepatitis B virus genome sequence and constitutes the first discovery of a Mesozoic paleovirus genome. We show that Hepadnaviridae are greater than 63 million years older than previously known and provide direct evidence for coexistence of hepatitis B viruses and birds during the Mesozoic and Cenozoic Eras. Finally, phylogenetic analyses and distribution of hepatitis B virus relics suggest that birds potentially are the ancestral hosts of Hepadnaviridae and mammalian hepatitis B viruses probably emerged after a bird–mammal host switch. Our study reveals previously undiscovered and multi-faceted insights into prehistoric hepatitis B virus evolution and provides valuable resources for future studies, such as in-vitro resurrection of Mesozoic hepadnaviruses.
An international team of researchers has decoded the genome of a creature whose evolutionary history is both enigmatic and illuminating: the African coelacanth. A sea-cave dwelling, five-foot long fish with limb-like fins, the coelacanth was once thought to be extinct. A living coelacanth was discovered off the African coast in 1938, and since then, questions about these ancient-looking fish – popularly known as "living fossils" – have loomed large. Coelacanths today closely resemble the fossilized skeletons of their more than 300-million-year-old ancestors. Its genome confirms what many researchers had long suspected: genes in coelacanths are evolving more slowly than in other organisms.
"We found that the genes overall are evolving significantly slower than in every other fish and land vertebrate that we looked at," said Jessica Alföldi, a research scientist at the Broad Institute and co-first author of a paper on the coelacanth genome, which appears in Nature this week. "This is the first time that we've had a big enough gene set to really see that."
Researchers hypothesize that this slow rate of change may be because coelacanths simply have not needed to change: they live primarily off of the Eastern African coast (a second coelacanth species lives off the coast of Indonesia), at ocean depths where relatively little has changed over the millennia.
"We often talk about how species have changed over time," said Kerstin Lindblad-Toh, scientific director of the Broad Institute's vertebrate genome biology group and senior author. "But there are still a few places on Earth where organisms don't have to change, and this is one of them. Coelacanths are likely very specialized to such a specific, non-changing, extreme environment – it is ideally suited to the deep sea just the way it is."
Because of their resemblance to fossils dating back millions of years, coelacanths today are often referred to as "living fossils" – a term coined by Charles Darwin. But the coelacanth is not a relic of the past brought back to life: it is a species that has survived, reproduced, but changed very little in appearance for millions of years. "It's not a living fossil; it's a living organism," said Alföldi. "It doesn't live in a time bubble; it lives in our world, which is why it's so fascinating to find out that its genes are evolving more slowly than ours."
The coelacanth genome has also allowed scientists to test other long-debated questions. For example, coelacanths possess some features that look oddly similar to those seen only in animals that dwell on land, including "lobed" fins, which resemble the limbs of four-legged land animals (known as tetrapods). Another odd-looking group of fish known as lungfish possesses lobed fins too. It is likely that one of the ancestral lobed-finned fish species gave rise to the first four-legged amphibious creatures to climb out of the water and up on to land, but until now, researchers could not determine which of the two is the more likely candidate.
In addition to sequencing the full genome – nearly 3 billion "letters" of DNA – from the coelacanth, the researchers also looked at RNA content from coelacanth (both the African and Indonesian species) and from the lungfish. This information allowed them to compare genes in use in the brain, kidneys, liver, spleen and gut of lungfish with gene sets from coelacanth and 20 other vertebrate species. Their results suggested that tetrapods are more closely related to lungfish than to the coelacanth.
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By looking at what genes were lost when vertebrates came on land as well as what regulatory elements – parts of the genome that govern where, when, and to what degree genes are active – were gained, the researchers made several unusual discoveries:
- Sense of smell. The team found that many regulatory changes influenced genes involved in smell perception and detecting airborne odors. They hypothesize that as creatures moved from sea to land, they needed new means of detecting chemicals in the environment around them.
- Immunity. The researchers found a significant number of immune-related regulatory changes when they compared the coelacanth genome to the genomes of animals on land. They hypothesized that these changes may be part of a response to new pathogens encountered on land.
- Evolutionary development. Researchers found several key genetic regions that may have been "evolutionarily recruited" to form tetrapod innovations such as limbs, fingers and toes, and the mammalian placenta. One of these regions, known as HoxD, harbors a particular sequence that is shared across coelacanths and tetrapods. It is likely that this sequence from the coelacanth was co-opted by tetrapods to help form hands and feet.
- Urea cycle. Fish get rid of nitrogen by excreting ammonia into the water, but humans and other land animals quickly convert ammonia into less toxic urea using the urea cycle. Researchers found that the most important gene involved in this cycle has been modified in tetrapods.
