Monthly Archives: July 2017

A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA (dsDNA) but may also be single-stranded DNA (ssDNA). DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses. Single-stranded DNA is usually expanded to double-stranded in infected cells. Although Group VII viruses such as hepatitis B contain a DNA genome, they are not considered DNA viruses according to the Baltimore classification, but rather reverse transcribing viruses because they replicate through an RNA intermediate. Notable diseases like smallpox, herpes, and chickenpox are caused by such DNA viruses.

Genome organization within this group varies considerably. Some have circular genomes (Baculoviridae, Papovaviridae and Polydnaviridae) while others have linear genomes (Adenoviridae, Herpesviridae and some phages). Some families have circularly permuted linear genomes (phage T4 and some Iridoviridae). Others have linear genomes with covalently closed ends (Poxviridae and Phycodnaviridae).

A virus infecting archaea was first described in 1974. Several others have been described since: most have head-tail morphologies and linear double-stranded DNA genomes. Other morphologies have also been described: spindle shaped, rod shaped, filamentous, icosahedral and spherical. Additional morphological types may exist.

Orders within this group are defined on the basis of morphology rather than DNA sequence similarity. It is thought that morphology is more conserved in this group than sequence similarity or gene order which is extremely variable. Three orders and 31 families are currently recognised. A fourth orderMegaviralesfor the nucleocytoplasmic large DNA viruses has been proposed.[1] Four genera are recognised that have not yet been assigned a family.

Fifteen families are enveloped. These include all three families in the order Herpesvirales and the following families: Ascoviridae, Ampullaviridae, Asfarviridae, Baculoviridae, Fuselloviridae, Globuloviridae, Guttaviridae, Hytrosaviridae, Iridoviridae, Lipothrixviridae, Nimaviridae and Poxviridae.

Bacteriophages (viruses infecting bacteria) belonging to the families Tectiviridae and Corticoviridae have a lipid bilayer membrane inside the icosahedral protein capsid and the membrane surrounds the genome. The crenarchaeal virus Sulfolobus turreted icosahedral virus has a similar structure.

The genomes in this group vary considerably from ~10 kilobases to over 2.5 megabases in length. The largest bacteriophage known is Klebsiella Phage vB_KleM-RaK2 which has a genome of 346 kilobases.[2]

A recently proposed clade is the Megavirales which includes the nucleocytoplasmic large DNA viruses.[1][3] This proposal has yet to be ratified by the ICTV.

The virophages are a group of viruses that infect other viruses. Their classification has yet to be decided. A family Lavidaviridae has been proposed for the genera Mavirus and Sputnikvirus.[4]

A virus with a novel method of genome packing infecting species of the genus Sulfolobus has been described.[5] As this virus does not resemble any known virus it seems likely that a new family will be created for it.

Species of the order Caudovirales and of the families Corticoviridae and Tectiviridae infect bacteria.

Species of the order Ligamenvirales and the families Ampullaviridae, Bicaudaviridae, Clavaviridae, Fuselloviridae, Globuloviridae, Guttaviridae and Turriviridae infect hyperthermophilic archaea species of the Crenarchaeota.

Species of the order Herpesvirales and of the families Adenoviridae, Asfarviridae, Iridoviridae, Papillomaviridae, Polyomaviridae and Poxviridae infect vertebrates.

Species of the families Ascovirus, Baculovirus, Hytrosaviridae, Iridoviridae and Polydnaviruses and of the genus Nudivirus infect insects.

Species of the family Mimiviridae and the species Marseillevirus, Megavirus, Mavirus virophage and Sputnik virophage infect protozoa.

Species of the family Nimaviridae infect crustaceans.

Species of the family Phycodnaviridae and the species Organic Lake virophage infect algae. These are the only known dsDNA viruses that infect plants.

Species of the family Plasmaviridae infect species of the class Mollicutes.

Species of the family Pandoraviridae infect amoebae.

Species of the genus Dinodnavirus infect dinoflagellates. These are the only known viruses that infect dinoflagellates.

Species of the genus Rhizidiovirus infect stramenopiles. These are the only known dsDNA viruses that infect stramenopiles.

Species of the genus Salterprovirus and Sphaerolipoviridae infect species of the Euryarchaeota.

A group known as the pleolipoviruses, although having a similar genome organisation, differ in having either single or double stranded DNA genomes.[6] Within the double stranded forms have runs of single stranded DNA.[7] These viruses have been placed in the family Pleolipoviridae.[8] This family has been divided in three genera: Alphapleolipovirus, Betapleolipovirus and Gammapleolipovirus.

These viruses are nonlytic and form virions characterized by a lipid vesicle enclosing the genome.[9] They do not have nucleoproteins. The lipids in the viral membrane are unselectively acquired from host cell membranes. The virions contain two to three major structural proteins, which either are embedded in the membrane or form spikes distributed randomly on the external membrane surface.

This group includes the following viruses:

Although bacteriophages were first described in 1927, it was only in 1959 that Sinshemer working with phage Phi X 174 showed that they could possess single-stranded DNA genomes.[10][11] Despite this discovery until relatively recently it was believed that the majority of DNA viruses belonged to the double-stranded clade. Recent work suggests that this may not be the case with single-stranded viruses forming the majority of viruses found in sea water, fresh water, sediment, terrestrial, extreme, metazoan-associated and marine microbial mats.[12][13] Many of these "environmental" viruses belong to the family Microviridae.[14] However, the vast majority has yet to be classified and assigned to genera and higher taxa. Because most of these viruses do not appear to be related or are only distantly related to known viruses additional taxa will be created for these.

Although ~50 archaeal viruses are known, all but two have double stranded genomes. These two viruses have been placed in the families Pleolipoviridae and Spiraviridae

Families in this group have been assigned on the basis of the nature of the genome (circular or linear) and the host range. Ten families are currently recognised.

A division of the circular single stranded viruses into four types has been proposed.[15] This division seems likely to reflect their phylogenetic relationships.

Type I genomes are characterized by a small circular DNA genome (approximately 2-kb), with the Rep protein and the major open reading frame (ORF) in opposite orientations. This type is characteristic of the circoviruses, geminiviruses and nanoviruses.

Type II genomes have the unique feature of two separate Rep ORFs.

Type III genomes contain two major ORFs in the same orientation. This arrangement is typical of the anelloviruses.

Type IV genomes have the largest genomes of nearly 4-kb, with up to eight ORFs. This type of genome is found in the Inoviridae and the Microviridae.

Given the variety of single stranded viruses that have been described this schemeif it is accepted by the ICTVwill need to be extended.

The families Bidnaviridae and Parvoviridae have linear genomes while the other families have circular genomes. The Bidnaviridae have a two part genome and infect invertebrates. The Inoviridae and Microviridae infect bacteria; the Anelloviridae and Circoviridae infect animals (mammals and birds respectively); and the Geminiviridae and Nanoviridae infect plants. In both the Geminiviridae and Nanoviridae the genome is composed of more than a single chromosome. The Bacillariodnaviridae infect diatoms and have a unique genome: the major chromosome is circular (~6 kilobases in length): the minor chromosome is linear (~1 kilobase in length) and complementary to part of the major chromosome. Members of the Spiraviridae infect archaea. Members of the Genomoviridae infect fungi.

All viruses in this group require formation of a replicative forma double stranded DNA intermediatefor genome replication. This is normally created from the viral DNA with the assistance of the host's own DNA polymerase.

In the 9th edition of the viral taxonomy of the ICTV (published 2011) the Bombyx mori densovirus type 2 was placed in a new familythe Bidnaviridae on the basis of its genome structure and replication mechanism. This is currently the only member of this family but it seems likely that other species will be allocated to this family in the near future.

A new genus Bufavirus was proposed on the basis of the isolation of two new viruses from human stool.[16] Another member of this genusmegabat bufavius 1has been reported from bats.[17] The human viruses have since been renamed Primate protoparvovirus and been placed in the genus Protoparvovirus.[18][19]

The most recently introduced family of ssDNA viruses is the Genomoviridae (the family name is an acronym derived from geminivirus-like, no movement protein).[20]

The family includes 9 genera, namely Gemycircularvirus, Gemyduguivirus, Gemygorvirus, Gemykibivirus, Gemykolovirus, Gemykrogvirus, Gemykroznavirus, Gemytondvirus and Gemyvongvirus.[21]

The genus name Gemycircularvirus stands for Gemini-like myco-infecting circular virus.[22][23] the type species of the genus Gemycircularvirus - Sclerotinia sclerotiorum hypovirulence associated DNA virus 1 - is currently the only cultivated member of the family.[20] The rest of genomoviruses are uncultivated and have been discovered using metagenomics techniques.[21]

Isolates from this group have also been isolated from the cerebrospinal fluid and brains of patients with multiple sclerosis.[24]

A isolate from this group has also been identified in a child with encephalitis.[25]

Viruses from this group have also been isolated from the blood of HIV+ve patients.[26]

Ostrich faecal associated ssDNA virus has been placed in the genus Gemytondvirus. Rabbit faecal associated ssDNA virus has been placed in the genus Gemykroznavirus.

Another virus from this group has been isolated from mosquitoes.[27]

Ten new circular viruses have been isolated from dragonfly larvae.[28] The genomes range from 1628 to 2668 nucleotides in length. These dragonfly viruses have since been placed in the Gemycircularviridae.

Additional viruses from this group have been reported from dragonflies and damselflies.[29]

Three viruses in this group have been isolated from plants.[30]

A virus Cassava associated circular DNA virus that has some similarity to Sclerotinia sclerotiorum hypovirulence associated DNA virus 1 has been isolated.[31] This virus has been placed in the Gemycircularviridae.

Some of this group of viruses may infect fungi.[32]

A number of additional single stranded DNA viruses have been described but are as yet unclassified.

Viruses in this group have been isolated from other cases of encephalitis, diarrhoea and sewage.[33]

Two viruses have been isolated from human faeces circo-like virus Brazil hs1 and hs2 with genome lengths of 2526 and 2533 nucleotides respectively.[34] These viruses have four open reading frames. These viruses appear to be related to three viruses previously isolated from waste water, a bat and from a rodent.[35] This appears to belong to a novel group.

A novel species of virus - human respiratory-associated PSCV-5-like virus - has been isolated from the respiratory tract.[36] The virus is approximately 3 kilobases in length and has two open reading frames - one encoding the coat protein and the other the DNA replicase. The significance - if any - of this virus for human disease is unknown presently.

An unrelated group of ssDNA viruses, also discovered using viral metagenomics, includes the species bovine stool associated circular virus and chimpanzee stool associated circular virus.[37] The closest relations to this genus appear to be the Nanoviridae but further work will be needed to confirm this. Another isolate that appears to be related to these viruses has been isolated from pig faeces in New Zealand.[38] This isolate also appears to be related to the pig stool-associated single-stranded DNA virus. This virus has two large open reading frames one encoding the capsid gene and the other the Rep gene. These are bidirectionally transcribed and separated by intergenic regions. Another virus of this group has been reported again from pigs.[39] A virus from this group has been isolated from turkey faeces.[40] Another ten viruses from this group have been isolated from pig faeces.[41] Viruses that appear to belong to this group have been isolated from other mammals including cows, rodents, bats, badgers and foxes.[32]

Another virus in this group has been isolated from birds.[42]

Fur seal feces-associated circular DNA virus was isolated from the faeces of a fur seal (Arctocephalus forsteri) in New Zealand.[43] The genome has 2 main open reading frames and is 2925 nucleotides in length. Another virus - porcine stool associated virus 4[44] - has been isolated. It appears to be related to the fur seal virus.

Two viruses have been described from the nesting material yellow crowned parakeet (Cyanoramphus auriceps) Cyanoramphus nest-associated circular X virus (2308 nt) and Cyanoramphus nest-associated circular K virus (2087 nt)[45] Both viruses have two bidirectional open reading frames. Within these are the rolling-circle replication motifs I, II, III and the helicase motifs Walker A and Walker B. There is also a conserved nonanucleotide motif required for rolling-circle replication. CynNCKV has some similarity to the picobiliphyte nano-like virus (Picobiliphyte M5584-5)[46] and CynNCXV has some similarity to the rodent stool associated virus (RodSCV M-45).[47]

A virus with a circular genome sea turtle tornovirus 1 has been isolated from a sea turtle with fibropapillomatosis.[48] It is sufficiently unrelated to any other known virus that it may belong to a new family. The closest relations seem to be the Gyrovirinae. The proposed genus name for this virus is Tornovirus.

Among these are the parvovirus-like viruses. These have linear single-stranded DNA genomes but unlike the parvoviruses the genome is bipartate. This group includes Hepatopancreatic parvo-like virus and Lymphoidal parvo-like virus. A new family Bidensoviridae has been proposed for this group but this proposal has not been ratified by the ICTV to date.[49] Their closest relations appear to be the Brevidensoviruses (family Parvoviridae).[50]

A virus Acheta domesticus volvovirus - has been isolated from the house cricket (Acheta domesticus).[51] The genome is circular, has four open reading frames and is 2,517 nucleotides in length. It appears to be unrelated to previously described species. The genus name Volvovirus has been proposed for these species.[52] The genomes in this genus are ~2.5 nucleotides in length and encode 4 open reading frames.

Two new viruses have been isolated from the copepods Acartia tonsa and Labidocera aestiva Acartia tonsa copepod circo-like virus and Labidocera aestiva copepod circo-like virus respectively.

A virus has been isolated from the mud flat snail (Amphibola crenata).[53] This virus has a single stranded circular genome of 2351 nucleotides that encoded 2 open reading frames that are oriented in opposite directions. The smaller open reading frame (874 nucleotides) encodes a protein with similarities to the Rep (replication) proteins of circoviruses and plasmids. The larger open reading frame (955 nucleotides) has no homology to any currently known protein.

An unusual and as yet unnamed virus has been isolated from the flatwom Girardia tigrina.[54] Because of its genome organisation, this virus appears to belong to an entirely new family. It is the first virus to be isolated from a flatworm.

From the hepatopancreas of the shrimp (Farfantepenaeus duorarum) a circular single stranded DNA virus has been isolated.[55] This virus does not appear to cause disease in the shrimp.

A circo-like virus has been isolated from the shrimp (Penaeus monodon).[56] The 1,777-nucleotide genome is circular and single stranded. It has some similarity to the circoviruses and cycloviruses.

Ten viruses have been isolated from echinoderms.[57] All appear to belong to as yet undescribed genera.

A circular single stranded DNA virus has been isolated from a grapevine.[58] This species may be related to the family Geminiviridae but differs from this family in a number of important respects including genome size.

Several viruses baminivirus, nepavirus and niminivirus related to geminvirus have also been reported.[32]

A virus - Ancient caribou feces associated virus - has been cloned from 700-y-old caribou faeces.[59]

More than 600 single-stranded DNA viral genomes were identified in ssDNA purified from seawater .[60] These fell into 129 genetically distinct groups that had no recognizable similarity to each other or to other virus sequences, and thus many likely represent new families of viruses. Of the 129 groups, eleven were much more abundant than the others, and although their hosts have yet to be identified, they are likely to be eukaryotic phytoplankton, zooplankton and bacteria.

A virus Boiling Springs Lake virus appears to have evolved by a recombination event between a DNA virus (circovirus) and an RNA virus (tombusvirus).[61] The genome is circular and encodes two proteinsa Rep protein and a capsid protein.

Further reports of viruses that appear to have evolved from recombination events between ssRNA and ssDNA viruses have been made.[62]

A new virus has been isolated from the diatom Chaetoceros setoensis.[63] It has a single stranded DNA genome and does not appear to be a member of any previously described group.

A virus - FLIP (Flavobacterium-infecting, lipid-containing phage) - has been isolated from a lake.[64] This virus has a circular ssDNA genome (9,174 nucleotides) and an internal lipid membrane enclosed in a icosahedral capsid. The capsid organisation is he capsid organization pseudo T = 21 dextro. The major capsid protein has two -barrels. The capsid organisation is similar to bacteriophage PM2 - a double stranded bacterial virus.

Satellite viruses are small viruses with either RNA or DNA as their genomic material that require another virus to replicate. There are two types of DNA satellite virusesthe alphasatellites and the betasatellitesboth of which are dependent on begomoviruses. At present satellite viruses are not classified into genera or higher taxa.

Alphasatellites are small circular single strand DNA viruses that require a begomovirus for transmission. Betasatellites are small linear single stranded DNA viruses that require a begomovirus to replicate.

Phylogenetic relationships between these families are difficult to determine. The genomes differ significantly in size and organisation. Most studies that have attempted to determine these relationships are based either on some of the more conserved proteinsDNA polymerase and othersor on common structural features. In general most of the proposed relationships are tentative and have not yet been used by the ICTV in their classification.

While determining the phylogenetic relations between the various known clades of viruses is difficult, on a number of grounds the herpesviruses and caudoviruses appear to be related.

While the three families in the order Herpesvirales are clearly related on morphological grounds, it has proven difficult to determine the dates of divergence between them because of the lack of gene conservation.[65] On morphological grounds they appear to be related to the bacteriophagesspecifically the Caudoviruses.

The branching order among the herpesviruses suggests that Alloherpesviridae is the basal clade and that Herpesviridae and Malacoherpesviridae are sister clades.[66] Given the phylogenetic distances between vertebrates and molluscs this suggests that herpesviruses were initially fish viruses and that they have evolved with their hosts to infect other vertebrates.

The vertebrate herpesviruses initially evolved ~400 million years ago and underwent subsequent evolution on the supercontinent Pangaea.[67] The alphaherpesvirinae separated from the branch leading to the betaherpesvirinae and gammaherpesvirinae about 180 million years ago to 220 million years ago.[68] The avian herpes viruses diverged from the branch leading to the mammalian species.[69] The mammalian species divided into two branchesthe Simplexvirus and Varicellovirus genera. This latter divergence appears to have occurred around the time of the mammalian radiation.

Several dsDNA bacteriophages and the herpesviruses encode a powerful ATP driven DNA translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The critical components of the packaging machine are the packaging enzyme (terminase) which acts as the motor and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex consists of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase) and cuts viral genome concatemers. It forms a motor complex containing five large terminase subunits. The terminase-viral DNA complex docks on the portal vertex. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. Only a single gene encoding the putative ATPase subunit of the terminase (UL15) is conserved among all herpesviruses. To a lesser extent this gene is also found in T4-like bacteriophages suggesting a common ancestor for these two groups of viruses.[70] Another paper has also suggested that herpesviruses originated among the bacteriophages.[71]

A common origin for the herpesviruses and the caudoviruses has been suggested on the basis of parallels in their capsid assembly pathways and similarities between their portal complexes, through which DNA enters the capsid.[72] These two groups of viruses share a distinctive 12-fold arrangement of subunits in the portal complex. A second paper has suggested an evolutionary relationship between these two groups of viruses.[71]

It seems likely that the tailed viruses infecting the archaea are also related to the tailed viruses infecting bacteria.[73][74]

The nucleocytoplasmic large DNA virus group (Asfarviridae, Iridoviridae, Marseilleviridae, Mimiviridae, Phycodnaviridae and Poxviridae) along with three other familiesAdenoviridae, Cortiviridae and Tectiviridae and the phage Sulfolobus turreted icosahedral virus and the satellite virus Sputnik all possess double -barrel major capsid proteins suggesting a common origin.[75]

Several studies have suggested that the family Ascoviridae evolved from the Iridoviridae.[76][77][78][79] A study of the Iridoviruses suggests that the Iridoviridae, Ascoviridae and Marseilleviridaeare are related with Ascoviruses most closely related to Iridoviruses.[80]

The family Polydnaviridae may have evolved from the Ascoviridae.[81] Molecular evidence suggests that the Phycodnaviridae may have evolved from the family Iridoviridae.[82] These four families (Ascoviridae, Iridoviridae, Phycodnaviridae and Polydnaviridae) may form a clade but more work is needed to confirm this.

Some of the relations among the large viruses have been established.[83] Mimiviruses are distantly related to Phycodnaviridae. Pandoraviruses share a common ancestor with Coccolithoviruses within the Phycodnaviridae family.[84] Pithoviruses are related to Iridoviridae and Marseilleviridae.

Based on the genome organisation and DNA replication mechanism it seems that phylogenetic relationships may exist between the rudiviruses (Rudiviridae) and the large eukaryal DNA viruses: the African swine fever virus (Asfarviridae), Chlorella viruses (Phycodnaviridae) and poxviruses (Poxviridae).[85]

Based on the analysis of the DNA polymerase the genus Dinodnavirus may be a member of the family Asfarviridae.[86] Further work on this virus will required before a final assignment can be made.

Based on the analysis of the coat protein, Sulfolobus turreted icosahedral virus may share a common ancestry with the Tectiviridae.

The families Adenoviridae and Tectiviridae appear to be related structurally.[87]

Baculoviruses evolved from the nudiviruses 310 million years ago.[88][89]

The Hytrosaviridae are related to the baculoviruses and to a lesser extent the nudiviruses suggesting they may have evolved from the baculoviruses.[90]

The Nimaviridae may be related to nudiviruses and baculoviruses.[91]

The Nudiviruses seem to be related to the polydnaviruses.[92]

A protein common to the families Bicaudaviridae, Lipotrixviridae and Rudiviridae and the unclassified virus Sulfolobus turreted icosahedral virus is known suggesting a common origin.[93]

Examination of the pol genes that encode the DNA dependent DNA polymerase in various groups of viruses suggests a number of possible evolutionary relationships.[94] All know viral DNA polymerases belong to the DNA pol families A and B. All possess a 3'-5'-exonuclease domain with three sequence motifs Exo I, Exo II and Exo III. The families A and B are distinguishable with family A Pol sharing 9 distinct consensus sequences and only two of them are convincingly homologous to sequence motif B of family B. The putative sequence motifs A, B, and C of the polymerase domain are located near the C-terminus in family A Pol and more central in family B Pol.

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DNA virus - Wikipedia

NEW YORK -- At Jef Boeke's lab, you can whiff an odor that seems out of place, as if they were baking bread here.

But he and his colleagues are cooking up something else altogether: yeast that works with chunks of man-made DNA.

Scientists have long been able to make specific changes in the DNA code. Now, they're taking the more radical step of starting over, and building redesigned life forms from scratch. Boeke, a researcher at New York University, directs an international team of 11 labs on four continents working to "rewrite" the yeast genome, following a detailed plan they published in March.

Their work is part of a bold and controversial pursuit aimed at creating custom-made DNA codes to be inserted into living cells to change how they function, or even provide a treatment for diseases. It could also someday help give scientists the profound and unsettling ability to create entirely new organisms.

The genome is the entire genetic code of a living thing. Learning how to make one from scratch, Boeke said, means "you really can construct something that's completely new."

The research may reveal basic, hidden rules that govern the structure and functioning of genomes. But it also opens the door to life with new and useful characteristics, like microbes or mammal cells that are better than current ones at pumping out medications in pharmaceutical factories, or new vaccines. The right modifications might make yeast efficiently produce new biofuels, Boeke says.

Some scientists look further into the future and see things like trees that purify water supplies and plants that detect explosives at airports and shopping malls.

Also on the horizon is redesigning human DNA. That's not to make genetically altered people, scientists stress. Instead, the synthetic DNA would be put into cells, to make them better at pumping out pharmaceutical proteins, for example, or perhaps to engineer stem cells as a safer source of lab-grown tissue and organs for transplanting into patients.

Some have found the idea of remaking human DNA disconcerting, and scientists plan to get guidance from ethicists and the public before they try it.

Still, redesigning DNA is alarming to some. Laurie Zoloth of Northwestern University, a bioethicist who's been following the effort, is concerned about making organisms with "properties we cannot fully know." And the work would disturb people who believe creating life from scratch would give humans unwarranted power, she said.

"It is not only a science project," Zoloth said in an email. "It is an ethical and moral and theological proposal of significant proportions."

Rewritten DNA has already been put to work in viruses and bacteria. Australian scientists recently announced that they'd built the genome of the Zika virus in a lab, for example, to better understand it and get clues for new treatments.

At Harvard University, Jeffrey Way and Pamela Silver are working toward developing a harmless strain of salmonella to use as a vaccine against food poisoning from salmonella and E. coli, as well as the diarrhea-causing disease called shigella.

A key goal is to prevent the strain from turning harmful as a result of picking up DNA from other bacteria. That requires changing its genome in 30,000 places.

"The only practical way to do that," Way says, "is to synthesize it from scratch."

The cutting edge for redesigning a genome, though, is yeast. Its genome is bigger and more complex than the viral and bacterial codes altered so far. But it's well-understood and yeast will readily swap man-made DNA for its own.

Still, rewriting the yeast genome is a huge job.

It's like a chain with 12 million chemical links, known by the letters, A, C, G and T. That's less than one-hundredth the size of the human genome, which has 3.2 billion links. But it's still such a big job that Boeke's lab and scientists in the United States, Australia, China, Singapore, and the United Kingdom are splitting up the work. By the time the new yeast genome is completed, researchers will have added, deleted or altered about a million DNA letters.

Boeke compares a genome to a book with many chapters, and researchers are coming out with a new edition, with chapters that allow the book to do something it couldn't do before.

To redesign a particular stretch of yeast DNA, scientists begin with its sequence of code letters - nature's own recipe. They load that sequence into a computer, then tell the computer to make specific kinds of changes. For example one change might let them rearrange the order of genes, which might reveal strategies to make yeast grow better, says NYU researcher Leslie Mitchell.

Once the changes are made, the new sequence used as a blueprint. It is sent to a company that builds chunks of DNA containing the new sequence. Then these short chunks are joined together in the lab to build ever longer strands.

The project has so far reported building about one-third of the yeast genome. Boeke hopes the rest of the construction will be done by the end of the year. But he says it will take longer to test the new DNA and fix problems, and to finally combine the various chunks into a complete synthetic genome.

Last year, Boeke and others announced a separate effort, what is now called Genome Project-write or GP-write . It is chiefly focused on cutting the cost of building and testing large genomes, including human ones, by more than 1,000-fold within 10 years. The project is still seeking funding.

In the meantime, leaders of GP-write have started discussions of ethical, legal and social issues. And they realize the idea of making a human genome is a sensitive one.

"The notion that we could actually write a human genome is simultaneously thrilling to some and not so thrilling to others," Boeke said. "So we recognize this is going to take a lot of discussion."

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Scientists build DNA from scratch to alter life's blueprint - CBS News

A 63-year-old man serving a life sentence for the 1988 murder of a Lincoln woman has won a push to get new DNA testing on previously untested evidence that he thinks could clear him of the crime.

Herman Buckman has served more than 29 years for the first-degree murder of Denise Strawkowski. He is at the Nebraska State Penitentiary.

On Feb. 19, 1988, she was found dead in the front seat of her car in a ravine near U.S. 34 and Northwest 48th Street. Strawkowski had been shot twice in the head.

At a trial, prosecutors said Buckman had killed her over a drug debt. The Lancaster County jury found him guilty.

Last September, Buckman filed a motion for forensic DNA testing of biological material asking that testing be done on the victim's underwear, as well as the floor mat and steering wheel cover.

Buckman contends that the testing could point to someone else as her killer.

He said the state never tested the evidence before and that the floor mats and steering wheel cover hadn't shown up on an earlier inventory.

In an order late last week, Lancaster County District Judge Susan Strong sustained the motion over an objection by the County Attorney's office. And she appointed the Commission on Public Advocacy to represent Buckman.

It's not the first time Buckman has filed a petition under the DNA Testing Act, which enables convicted people to request DNA testing at state expense if it could lead to a new trial or to outright exoneration.

In 2004, he lost his bid for a new trial after testing on cigarette butts found at the crime scene were inconclusive.

At best, Buckman could neither be included or excluded as being a contributor of some of the genetic material found on the tested cigarettes, according to the Nebraska Supreme Court opinion.

In 2001, Buckman petitioned the Lancaster County District Court for DNA testing on bloodied clothing belonging to him, and on cigarette butts found in the back seat of the car in which Stawkowski was murdered.

A judge approved the testing, but the examination of the clothing found no blood traces to test; and testing on the cigarette butts was inconclusive, partly because of contamination during storage.

At the 1988 trial, an expert witness for the state testified the butts had blood substances consistent with Buckman's blood type.

The later tests found DNA from more than one person, one of whom could have been Buckman.

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Judge OKs DNA testing in 1988 Lincoln murder case - Lincoln Journal Star