Bio-molecular signatures associated with psychiatric disorders

This article investigates utilizing methylation profiles at CpG I of the BDNF gene in diagnosing depressive disorders.

Q&A with Leroy E. Hood

This article is a Q&A with Leroy Hood. Hood pioneered the automated DNA sequencer while at Caltech in the 1980s, and more recently has he been a vocal proponent of the Human Genome Project. In this interview, Hood fields questions about the progress in the field of personal genomics, commenting upon the recent wealth of data available to people who wish to sequence themselves and the benefits of potential medical applications of this data.

Genomic parasites responsible for the birth of mammalian pregnancy

I thought this was pretty wild - and it happened right across the street in ESC!

Gunter Wagner (and team) set out to investigate novel phenotypes/cell types - in particular, mammalian pregnancy. How did carrying developing young in the womb evolve?

Wagner and team identified 1500 genes that were unique to the uterus of mammals and involved in placental development. The big kicker? The expression of these genes is under control by transposons. Essentially, large-scale morphological changes (aka - the emergence of mammalian pregnancy) was not due to mutations within key genes, but rather is attributable to the establishment of a novel gene regulatory network (modulated by transposons).

Processed pseudogenes: the 'fossilized footprints' of past gene expression

Though modern technology has allowed the access and sequencing of ancient DNA, evolutionary geneticists would like to access ancient ancestral organisms' transcriptomes in order to investigate more into the evolution of gene expression. Because of the fragility of mRNA and therefore near impossibility of ancient extraction, researchers want to use pseudogenes, which are non-functioning relatives of existing genes that no longer code for proteins. Each expressed gene purportedly has a certain number of "pseudogene offspring", and so researchers believe that these genes can be used as "fossilized footprints" of former gene expression. This process is not wholly accurate, and researchers stress the usefulness of extracting ancient transcriptome information for future studies of evolution.

Ancient DNA extraction techniques in ancient bone

Archaeological research attempting to isolate ancient DNA from skeletal material has met with many difficulties. The issues of preservation, high potential for false negatives, and varied depositional environments have all proved to be confounding factors when attempting to extract genetic material from ancient remains. This study utilizes PCR analysis to measure (mt)DNA quantities in various hard tissues in ancient human and bovid material in order to determine the most promising regions of bone for this type of analysis. They found that using a low speed drill as opposed to high speed drilling or bone pulverization yielded significantly more (mt)DNA. In addition, they found that tooth cementum, as opposed to the more commonly utilized tooth dentin yielded the most (mt)DNA. Finally they found that different types of skeletal material exhibit consistent patterns of exponential fragmentation across varied types of depositional environments.

Evolution's past is modern human's present

In this article it is explained that modern African populations interbred with "archaic" humans. The study, done by Michael Hammer and his team, took the DNA sequence from 3 different African groups and found that part of their genome comes from archaic humans who were biologically compatible to the point of producing fertile offspring. Although fossils have not yet been found to support the findings done by this research, the researchers were able to infer based upon the very thorough simulations that were done. The groups that existed in the past are believed to have come from Central Africa. The article also suggested that interbreeding with archaic humans in Africa lasted much longer than interbreeding in Europe or Southeast Asia.

Cloning of Neanderthals?

Like homo sapiens, the Neanderthals were smart, made tools, and had a complex social system that involved the respectful burial of the dead. And yet, it was our ancestors who survived and not this seemingly equally viable sister species. Sequencing the Neanderthal DNA has allowed scientists to pinpoint their evolutionary relationship to us, answer fascinating questions about their intelligence in relation to ours and whether or not we interbred, and allowed scientists to hazard guesses as to the cause of their downfall, which will inevitably shine light onto our own vulnerabilities. However, along with this insight from a complete genome sequencing of Neanderthal DNA comes the moral question of cloning. Cloning is a complicated process involving the replacement of a nucleus of a stem cell with a nucleus containing the genome of the desired parent. Sequencing the DNA of a deceased organism is already complicated, but that would only be the start (the really tricky part is synthesizing the nucleus, which scientists believe could be accomplished by individually altering the genetic material of a human nucleus, nucleotide by nucleotide). Thus, we are definitely quite a ways away from a cloned Neanderthal, but the idea definitely represents yet another interesting moral dilemma that genome sequencing brings to light. Cloning in general raises moral issues, in the creation of life as "playing God" and in the use of fetal stem cells. However, there is also the issue of bringing back a species whose natural ecosystem has long-since been destroyed, a world in which it can exist only under study in a laboratory. This issue is even more controversial as it is no ordinary extinct species (like the wooly mammoth that scientists at Kyoto University in Japan intend to reserect), but our own sister species, a species that science indicates to have potentially been as sentient and conscious as we are. To clone a Neanderthal would inevitably bring into discussion cloning of one of our own.

Neanderthal-human Hybrids

Mason and Short propose a solution to the apparent paradox of human-neandertal hybridization: that is, that human mtDNA shows no trace of neandertal lineage and there are few Y-linked neandertal genes in the human genome, yet autosomal DNA shows clear evidence of interbreeding. They suggest that only male neandertals were able to mate with female humans, perhaps due to the larger size and dominance of male neandertals over the human females which would not have existed for female neandertals over male humans. They add that Haldane's Law tells us that heterogametic offspring are often sterile, if even viable, and therefore XY offspring of any interbreeding would not contribute further to the human gene pool. Left would be females with human mtDNA but autosomal components from their paternal neandertal lines.

Ancient Genetic Mixing Seen in Immune System Genes

While it was thought that many of the places in the genome that Neanderthal and Denisovan DNA mixed with modern human's were non-functional, this study shows that this mixing had profound impact on the modern human immune system.  This report looked specifically at HLA genes (coding for HLA proteins).  In European, Asian, and New Guinea populations, more than half the genetic variation in the HLA gene can be attributed to ancient genomic mixing.  The article suggests that this mixing was a way for modern human ancestors to acclimate to new bacteria when moving out of Africa.

Genetic evidence for patrilocal mating behavior among Neandertal groups

This study looked at the mtDNA (HVR 1 and 2) Of a group of Neandertal fossils that were buried at the El Sidrón site in Spain. These individuals are believed to represent a "contemporaneous social group" in that they were buried together as the result of a karst collapse. The mtDNA of the individuals revealed three different maternal lines. They also sexed the fossils (using Y chromosomes) and discovered that the males shared an mtDNA haplogroup while the adult females did not. This led the researchers to conclude that this group of Neandertals was patrilocal.

NCBI Epigenomics

NCBI has launched their epigenomics browser. Think of this as your one-stop shopping for epigenetics information. It compiles all of the studies done in epigenetics, and allows you to search by gene, cell line or organ. This will be a great way to keep track of the explosion of studies and information concerning epigenetics!

http://www.ncbi.nlm.nih.gov/epigenomics

X-linked evidence of a Neandertal genetic contribution to non-africans

This study further confirms the results of the Green et al., (2010) draft of the Neandertal genome. They found an allelic variation of the dystrophin gene that is found exclusively in non-Africans and is shared with Neandertals. This supports the idea that Neandertals contributed to the H. sapiens nuclear genome. Furthermore, it supports a model of contribution that occurred after the first migration from Africa, but before successful colonization of the rest of the globe. The only exception to this finding is that the allele in question was also found in Massai populations. This is explained by a "back-to-Africa" migration hypothesis, but still makes me a bit concerned.

Access the full PDF HERE, and the news briefing HERE.

Strong reproductive isolation between humans and Neanderthals inferred from observed patterns of introgression

Recent highly publicized studies suggest that interbreeding between modern humans and Neanderthals accounts for 1 to 4% of the genome of present-day non-Africans. Using the simulation program SPLATCHE2, Currat and Excoffier modeled differing scenarios of early human expansion in order to investigate the demographic history of early humans and Neanderthals. They found that 2-3% Neanderthal ancestry in non-Africans can be accounted for by interbreeding rates of less than 2%, and suggest that this low rate may be an effect of such gene flow barriers as avoidance of interspecific mating and/or low fitness of hybrids. One scenario with a hybrid success rate of only 5% led to 80% Neanderthal introgression in modern Eurasians, further suggesting that interbreeding was very limited. The authors also suggest that different populations of Neanderthals may have interbred with Europeans and Asians after their division, which could be tested by comparing the specific genomic elements shared between Europeans and Neanderthals versus Asians and Neanderthals.

Denisova Admixture and the First Modern Human Dispersals into Southeast Asia and Oceania

Reich et al. recently published a new paper on Denisova admixture in Asia and Oceania in The American Journal of Human Genetics. They sampled 33 additional populations to those that were studied in previous papers to describe a more extensive migratory and population model for East and Southeast Asia and Oceania. The research showed that East Asian and western Indonesian populations did not show evidence of Denisovan material, which was present in aboriginal Australians, Polynesians, east Indonesians, and others. Therefore, they conclude that Denisova interbreeding with present-day humans occurred in Southeast Asia and happened before ancestors of present-day East Asians were in Southeast Asia. This challenges the model that the Denisova gene flow occurred in mainland Asia, the supposed geographical limits of the Denisova, and then spread to Southeast Asia; the authors instead suggest that this gene flow happened in Southeast Asia itself. These results broaden the previously-described geographic range of the Denisovans to more areas of Asia, and demonstrate their large "ecological range, from Siberia to tropical Asia."

First Aboriginal genome sequenced

Previous genetic studies on modern Asian and Oceanic populations have suggested a single migration that eventually led to all modern populations in Asia, Australia, and Oceania today. However, sequence analysis of this first aboriginal genome is strongly suggestive of two waves of migration. The first migrants branched off from African humans around 60,000 years ago and constituted the ancestors of modern Papua New Guineans, Australians, and Oceanians. The second wave of migrants were the ancestors of modern mainland Asians.

Further supporting this theory was the discovery that a small portion of the aboriginal genome is derived from Neanderthals and another small chunk is distinctly Denisovan. Papua New Guineans were previously thought to be the only population with Denisovan-derived DNA (until now!). Looks like that first wave of migrants were getting down and dirty, while the second wave kept it clean (to be fair, the Denisovans may have disappeared by the time of the second migration).

Spontaneous epigenetic variation in the Arabidopsis thaliana methylome

This is really cool. The authors studied epigenetic inheritance in a species of plant. The authors conclude that, while many epigenetic changes to last a few generations, over the long-term most are not stable and are reversed.

The Science Daily piece stresses the limited duration of these 'epimutations': "Epigenetic Changes Often Don’t Last, Probably Have Limited Effects On Long-Term Evolution, Research Finds." I tend to feel like they might be missing a bigger point: methylation is a response to short-term (a few generations) information about the environment. Would we expect that a plant would make epigenetic modifications based on current environmental conditions that would affect relatives 10 generations from now? If the environment were stable enough to warrant that duration of change, why wouldn't we expect that to be in the realm of DNA mutation?

Antibiotic resistance is ancient

An example of one of the many cool things we can do with ancient DNA!

Question: Is modern clinical antibiotic use responsible for the emergence of antibiotic resistance in bacteria?

Bacterial (ancient) DNA was isolated from 30,000 (!) year-old Beringian permafrost sediments. As with many aDNA studies - there's the problem of contamination. To establish authenticity (I found this part really neat), they amplified 12S rRNA and two chloroplast genes, then BLASTed the amplified fragments to ensure that the sequences matched late Pleistocene (not Holocene - the present geological epoch) flora and fauna. Once authenticity was established, they looked for the presence of resistance-conferring genes in these aDNA bacterial genomes - specifically resistance genes for tetracycline, penicillin, and vanomycin (as a side note, they also looked at genes responsible for "diverse strategies of drug evasion").

The big finding? The ancient bacteria already possessed genes conferring antibiotic resistance - highly similar to the genes we see in modern bacteria. Antibiotic resistance is ANCIENT. And not something that evolved via selection pressures caused by modern clinical antibiotic use.

50 new genes for recessive cognitive disorders

This new study looked at 136 families with autosomal-recessive cognitive disorders and discovered novel mutations in 23 genes that were previously known to be associated with cognitive disorders. Furthermore, they found *probable* disease-causing variants in 50 novel genes. The proteins coding for these 50 novel genes interact directly with previously identified gene products known to be implicated in cognitive disorders. Many of the proteins are integral for the processes responsible for normal brain development and function.

I'm sure these results will rapidly be transformed into a testing option for several personal genome sites...

Hand preferences for coordinated bimanual actions in 777 great apes: Implications for the evolution on handedness in Hominins

Population-level Right handedness is a universal trait of humans. In this article from the Journal of Human Evolution, researchers present an assessment of handedness in four great ape species. After conducting the TUBE test that requires bimanual actions on numerous samples of these different species, results showed that chimpanzees, bonobos, and gorillas all showed population-level right handedness, whereas orangutans showed population-level left handedness. Findings from this experiment were meant to be compared to the results from a similar 2003 experiment by Hopkins et al which used smaller population sizes and therefore produced potentially inaccurate data.

In this experiment, researchers considered many factors such as the influence of age, sex, and human rearing on species' hand preference, concluding age to be the only relevant factor in certain species. Additionally, there seems to be a focus on compiling accurate data for chimpanzees as man's closest nonhuman primate relative. The authors make a note that the lateralization of handedness is linked to language lateralization in humans, which suggests linked evolution. With this in mind, results from this experiment could shed more light on human-primate divergence.

Sex with Denisovans a double-edged sword?

Controversy continues as to whether or not archaic Homo populations contributed to modern human DNA, and if so, whether said DNA is functional. This summer, a large research project led primarily from Stanford suggested that hybridization with archaic populations resulted in the HLA gene repertoire we see today in modern populations, a crucial tool of the immune system used to recognize pathogens.

However there may have been a downside to the Neanderthal flings. High variability in immunity genes may be linked to autoimmune disorders, wherein the immune system turns on itself. In particular, the group are looking at the gene variant HLA-B51, which is thought to have been inherited from Neanderthals, and which has been shown to be linked to the inflammatory disorder Behcet's disease.

Oldest human skeleton offers new clues to evolution

The 2009 article challenges the belief that humans evolved from chimpanzees to support the belief that man and chimps evolved from a common ancestor many years ago. The discovery of this in-between species indicates that humans have been evolving for at least 6 million years. The 1994 discovery was named Ardipithecus ramidus--"Ardi" for short. Ardi's brain was similar to the size of a chimps and Ardi had an opposable toe for grasping branches but Ardi did have some human-like qualities. The fact that Ardi was discovered in Ethiopia is pretty important because this region is believed to be the birthplace of mankind.

Sequencing the chimpanzee genome: insights into human evolution and disease

This review, published in 2003 amidst growing hype surrounding the Chimpanzee Genome Project, explores the practical implications of chimpanzee-human genome comparison, focusing on biomedical applications. It addresses the use of such comparison to test the "less-is-more" hypothesis, which emphasizes the importance of loss of function mutations in the human lineage, and the hypothesis that phenotypic differences between humans and chimpanzees are caused by changes in gene regulation rather than in the protein repertoire.

RNA editing, DNA recoding and the evolution of human cognition

RNA editing appears to be the major mechanism by which environmental signals overwrite encoded genetic information to modify gene function and regulation, particularly in the brain. We suggest that the predominance of Alu elements in the human genome is the result of their evolutionary co-adaptation as a modular substrate for RNA editing, driven by selection for higher-order cognitive function. We show that RNA editing alters transcripts from loci encoding proteins involved in neural cell identity, maturation and function, as well as in DNA repair, implying a role for RNA editing not only in neural transmission and network plasticity but also in brain development, and suggesting that communication of productive changes back to the genome might constitute the molecular basis of long-term memory and higher-order cognition.

Methylation and gene sequence co-evolve in human-chimp evolutionary divergence

This new study from Cold Spring Harbor shows evidence that methylation has "co-evolved in a kind of molecular slow-dance over the 6 million years since humans and chimps diverged from a common ancestor." The authors explain that "by looking very closely at methylation patterns within individuals and across species, one can begin to piece together previously hidden stories about how species grew apart via evolution." They support the idea that "methylation changes could drive changes in DNA sequence." Since many of the papers we read this week looked strictly at the genetic code, this focus on methylation is an interesting perspective when considering evolutionary changes.

Ancient Human Demography from Individual Genome Sequences

This article estimates when ancient human populations diverged.  It used 6 individual genomes and a bunch of statistics to figure out when population splits between southern africans and the rest of the human population diverged, when eurasian populations diverged from african populations, and when european populations diverged from asian populations.

Increased exonic de nove mutation rate in individuals with schizophrenia

In this new study, scientists used sequencing of individuals with schizophrenia and their parentsin efforts to trace the genetic cause of the disease. They identified 15 de novo mutations associated with the inheritance of the disease. These findings will definitely play a significant role in the diagnosis, prediction, and treatment of the condition, and I expect that it will also play a large role in our society's view of mental illness, in both social settings and judicial systems when deciding on punishment for individuals suffering from the condition. However, as it is a highly complex disease, there are many contributing factors and genes, there is room for further research.

Genetic evidence for archaic admixture in Africa

"Here we use DNA sequence data gathered from 61 noncoding autosomal regions in a sample of three sub-Saharan African populations (Mandenka, Biaka, and San) to test models of African archaic admixture. We use two complementary approximate-likelihood approaches and a model of human evolution that involves recent population structure, with and without gene flow from an archaic population. Extensive simulation results reject the null model of no admixture and allow us to infer that contemporary African populations contain a small proportion of genetic material (≈2%) that introgressed ≈35 kya from an archaic population that split from the ancestors of anatomically modern humans ≈700 kya."

Whole exome resequencing in non-human primates

This study applied a human-specific whole exome resequencing to non-human primates and had fairly good results. This is a possible new method for detecting genetic variation in non-human primates and may help correct some of the current genome annotation issues for coding regions.

450k CpG Methylation Microarray NOW AVAILABLE!

This new illumina microarray is capable of analyzing methylation at 450,000 CpG sites in the human genome!!! This is a significant increase from 27,000 sites, the size of their previous 'big' assay. While it will likely be used mostly in cancer research, this could be a very interesting way to characterize methylation diversity across human populations. Do you think we will see more genetic or epigenetic variation?

CLICK HERE for the PDF

Personal Genomics is diversifying...

Gastrointestinal woes? MyMicrobiomes is inviting people to have their gut microbiomes sequenced.

Speaking of who the daddy is....

A little fun (click here)

PCR, when you need to find out who the daddy is!

Glowing Kittens Fight Feline AIDS

Scientists have genetically modified cats by infecting their eggs with a virus containing a foreign gene—the first time this method has worked in a carnivore. Experts say the advance could make the cat a valuable new genetic model—and potentially protect it from an HIV-like virus.

"One Sperm Donor, 150 Offspring"

It's about the large number of children sperm donors in the US are fathering because of the lack of regulation of sperm donation clinics (unlike the US). The article is mainly concerned with the fact that the fathers did not know about the large numbers of children they would be having, and the fact that the children of the sperm donors could have a lot of other half siblings, unbeknownst to them, and risk incestuous relationships.

It did touch on the fact that rare genetic diseases could then be more prevalent in the population because of this preponderance of offspring of a few individuals that could be carriers for a disease. But it also got me thinking, could you even consider this a sort of unnatural population drift? Maybe drift isn't the correct term, but it does seem like a overrepresentation in the gene pool of a few individuals. This has obviously happened before, bringing to mind the famous example of Ghengis Khan. But here we have a different situation where men who are not "actively" involved are fathering a ton of offspring. These men might not have been viable mates outside of the sperm clinic context for any number of reasons as well (or maybe they would be more likely to have many children ...I don't know anything about sociological aspects of sperm donors but I'm sure there's a study out there somewhere).

'Indians and Europeans share a milky past'

A new study from University of Cambridge demonstrates how the shared presence of the lactose tolerance-linked -13910T mutation might shed light on historical migratory events.

More Evidence that Human Evolution Wasn't Linear

New genomic analysis of African hunter-gatherer tribes seems to suggest that genetic mixing happened between ancient Homo species even before they left Africa.