Interspecies Epigenetic Comparison

Researchers studied CpG islands and methylation sites on chromosomes 21 and 22 in both humans and chimpanzees. It is believed that these differences in methylation cause minute transcriptional differences, resulting in small phenotypic changes. Interestingly, many of the genes showing interspecific differences are those that affect disease in humans, such as the Alzheimer's-associated APP, which was found to be more heavily methylated at exon 7 in humans. The ramifications of this study are as-yet unclear, particularly because manifestation of the disease is either markedly different or nonexistent in non-human primates.

Source: Click Here! (Journal of Human Genetics, 2013)

HIV and infectivity: recent developments

The most recent issue of Nature contains two articles about Nef, a protein of the HIV-1 virus which increases infectivity in a human host.

The authors of the two studies independently found that Nef inhibits two proteins of the host that have antiviral activity against HIV: SERINC3 and SERINC5.

This discovery has important implications for the fight against AIDS, as the development of a drug targeting Nef could prevent the virus from spreading from cell to cell within the host. But first, more research has to be done on the mechanisms by which SERINC3 and SERINC5 operate.

Source: aids. gov 

Searching for Human-Chimp Differences in HARs

Hubisz and Pollard recently reviewed the [recent] history and current state of research on Human Accelerated Regions (HARs). Since 2006 a series of studies have emerged regarding the discovery and exploration of HARs, regions of the human genome that have undergone rapid changes since our divergence from chimpanzees that are widely conserved in non-human organisms.

This methodological approach is distinct from positive selection studies which test for phylogenetic changes in the ratio of synonymous to non-synonymous mutations (dN/dS). In fact, as 96.6% of HARs are non-coding (ncHARs) and tend to cluster near genes, their function appears to be almost entirely regulatory. Many of these nearby genes are developmental transcription factors, and/or expressed in the central nervous system. These findings supports previous assertions that most of the morphological and cognitive differences between humans and non-human apes are regulatory in nature. By applying these same methods to the study of ancient DNA, it was also found that "7.1% of human–chimp differences in ncHARs occurred after divergence from archaic hominins [Neanderthals and Denisovans]."

That said, many ncHARs have not yet been annotated or lack experimentally established functions. Future exploration of these regions using transgenic animals models therefore hold promise in the search for what makes humans the way they are.

Tommy Can You Hear Me? Auditory Capabilities in Early Hominins

Language is beyond a doubt one of the cornerstone traits of humankind, and with the capability to speak comes the inexorable need to hear well. The sense of hearing originates of course from the external soft-tissue ear, but as well from the internal cranial structures at the temporal bones underlying ears. In a comparative anatomy study from Binghamton University in New York, researchers predict the auditory capabilities of individuals from the species Australopithecus africanus and Paranthropus robustus, with comparison to modern humans and chimpanzees. Analysing outer and middle ear bony structures, including preserved auditory ossicles from the South African hominins, the researchers determine that the two taxa are largely derived toward modern humans in their acoustic anatomy, but with more primitive incus and stapes resembling those of a chimpanzee. The study presents an interesting case study in the use of observable traits as proxies for interesting, more "intangible" properties of extinct organisms. To a cautious and limited extent, bone structure of the hominin inner ear allows prediction of power transmission for various frequencies of sound; with an understanding of the vibrational mechanics of different vocalisations, one can then make careful assumptions about the possible linguistic capabilities of these early hominins. The researchers in the study are careful not to take this to the level of science fiction, and so make respectable and exciting claims regarding the use of auditory capability to determine paleoenvironment, linguistic behavior and intraspecies variation thereof, and cladistic relationships. The closeness of Paranthropus and A. africanus acoustic cranial morphology to both modern humans and chimps implies some reliability of these as traits for systematic analysis; this could represent a new opportunity for improved understanding of ancient hominin phylogenies, as early fossils continue to enter our view of the dawn of humanity.

Fig. 1Measurements of the middle and outer ear (A to C) and ear ossicles (D). Quam et al Science Advances 2015

Short and overweight? Blame it on your ancestors

Height is of course controlled by countless genetic, environmental and social factors, but a study recently published in the journal Science reports one of the strongest genetic effects on height.

According to the study, ancestors of the Inuit from Greenland developed a unique ability to metabolize fatty acids, including omega-3 fats. Extreme environmental conditions would have created important selective pressures on the first inhabitants of the Arctic.

Present in almost 100% the individuals studied, the genetic adaptation observed mostly on chromosome 11, would have consequences on the Inuits' height and weight. Regulation of growth hormones is linked to a person's fatty acid profile and the participants of the study who carried both copies of the alleles were reported to be about two centimeters shorter and 10 pounds lighter than those who didn't.

In addition to sequencing the DNA of Inuits, the authors studied Chinese and Europeans (Greenland was colonized by Denmark), which all had much lower occurrences of this genetic variant (15% and 2% respectively).

Fish oil supplements and omega-3 pills might be obsolete: different diets affect people differently!

(P.S. Nutritional genomics is a thing)

The cellular basis of forgetting early childhood memories

Much of the following was reviewed in a recent Knowing Neurons blog entry.

Freud was one of the first psychologists to try and explain the phenomenon of "infantile amnesia"; the inability to remember early childhood experiences. As with many of his concepts, he proposed that this was a product of repressing the early psychosexual development in children. More recently, a cellular mechanism by which this occurs has been proposed. Neurogenesis, the production of new neurons, is a process that occurs primarily during development but extends into adulthood in two canonical neurogenic regions; one of which is the dentate gyrus (DG) of the hippocampus. The hippocampus is a structure that is critical for long-term episodic memory storage.

It had been previously suggested that the massive upregulation of neurogenesis in the DG during early childhood development blocks memory formation. When researchers took baby mice and selectively downregulated their DG neurogenesis, their performance on memory tasks improved significantly. Conversely, other studies that upregulated neurogenesis in adult mice after learning a task showed memory defecits. Later studies seemingly contradict this result, as Cre-lox trangenic mice that were induced to increase DG neurogenesis by 3.6 -fold in adult mice showed memory improvement. The key here is the order of events; increasing AN before a task is learned improves memory, whereas after a task was learned interferes with memory. The latter situation is much more akin to what happens in the developing brain which is adding new neurons both before and after and after childhood events occur.

Thus, it seems that during early childhood, the extended period during which human children are unable to form and retain long-term memories is a necessary cost for building a big, complex, and slow-growing brain.

The Infamous 99%

Often quoted but rarely understood is the pronouncement that humans and non-human primates share 98~99% of their DNA. In reading MC King and AC Wilson's "Evolution at two levels in humans and chimpanzees," it was fascinating to see the initial methodology used to arrive at the conclusion.
While enough scientific inquiries and improvements in genomic testing over time likely provided more evidence to support the claim than to deny it, however, there still remains the question of how to translate the data for a wider audience.


Jonathan Mark's "What it Means to be 98% Chimpanzee; Apes, People, and Their Genes" makes for an interesting read in this case as he simultaneously tries to support the statement while dispelling the misconceptions made not only by a lay-audience but also by members of the research community as well. His critique isn't all bad, however; answering the question of what it all really means has been the great motivator for ongoing research for decades and will likely continue for decades to come.

Relics of our Common Ancestor in Apes

The HAdV virus is highly common in the human genome. Not surprisingly, we share this very common ailment with some of our genealogical cousins, gorillas(which carry up to 55% of the gene) and chimpanzees(who hold up 25%). As the gene carried is hominid in origin, the article on Molecular Biology and Evolution seeks to understand how the gene has transferred between the different species and how it may relate to a common ancestral heritage. It also dives into the different species transfers of pathogens even touching on one of the most deadly diseases originating from primates, the HIV-1 virus.

Using mtDNA to track the timing and dispersal of modern humans out of Africa

Seminal research by Cann et al. in 1987 demonstrated the utility of mtDNA in understanding both the timing and geographic location of the emergence of modern humans. Just over a decade later Quintana-Murci et al (1999) use mtDNA to shed new light on the timing and route of the first dispersal of modern humans out of Africa, a discussion that has largely focused on the fossil and archaeological evidence. However, estimating timing and route of a dispersal out of Africa is difficult as the fossil and archaeological record in the areas imediately outside of Africa is sparse at best.  By calculating the coalescence time for haplogroup M mtDNA in east Africa and India, they were able to estimate that the first major dispersal of modern humans outside of Africa occured around 60,000 years ago by way of East Africa. This estimate puts the archaeological evidence surrounding modern human dispersals into some context. Based on their findings they also suggest that 100,000 year old skeletal and archaeological remains from Middle Eastern sites Skhul and Qafzeh represent a temporary sortie outside of Africa. 

Is face recognition heritable?

Face recognition, the ability to recognize and memorize faces, is one type of specific cognition that is often thought to be correlated with general cognition. A  recent article on PNAS that studied both identical and fraternal twins in the UK tested face recognition using Cambridge Face Memory Test (CFMT) along with object recognition test and general cognitive ability supports previous studies and indicates that face recognition is substantially heritable due to genetic influences that are highly specific to this ability. The study also notes that although correlated with object recognition and general cognitive abilities, face recognition is genetically independent.

Generation times and the molecular clock

The life history traits of humans are thought to very unique and have evolved very recently in their evolutionary history. According to the “Generation time effect hypothesis”, this slow life history of humans that resulted in a longer generation times, have also brought about slow rate of molecular evolution compared to our closest relatives due to accumulation of fewer substitutions. A study by Elango et al, which looked at single nucleotide substitution on a large-scale sequence comparisions, indicates that there is indeed a slow molecular evolution in humans compared to other Hominoids. However, the slight differences observed in comparisons with Pan indicate that this is a more recent development. The study also suggested that humans and chimpanzees have slower molecular clocks compared to gorillas and orangutans.

"Cellular Anthropology" - Why do human and chimpanzee faces differ?

There is overwhelming evidence that the morphological differences between closely related species, including chimpanzees and humans, are not due to sequence changes in proteins, but to regulation of gene expression. Recently, researchers from Stanford University were interested in pinpointing how and when during development did differences in chimpanzee and human facial morphology manifest.

Using iPSCs (induced pluripotent stem cells), they created chimp and human cranial neural crest cells, and examined differences in gene enhancer regions. Published in Cell, their results suggest that there are around 1,000 species-biased enhancers near loci involved in craniofacial development and facial variation. 

Epigenetic Testing For Substance Abuse - Ethical Concerns & Legal Questions

In a recent commentary published in Behavioral Sciences & the Law, Texas Tech University professor Cheryl Erwin, J.D., Ph.D. takes a look at the ethical and moral concerns surrounding tests and punishments for substance abuse and addiction.

As scientific understanding of the human epigenome, its function, and its capabilities have expanded, so too have ideas about how these may be employed to meet various needs. With research into how certain epigenetic traits predict or are affected by addiction and substance abuse, the possibility has risen of epigenetic testing to assess drug and alcohol issues among job applicants, welfare recipients, prospective parents, and automobile drivers. Dr. Erwin warns that the predictive nature of some epigenetic testing, wherein an individual's likelihood of a disease or disorder is assessed, has the tendency to lead to prejudice and unfair discrimination. Can an employer or a custody judge deny an American citizen's rights based on predictive biological signals, even if the individual is devoid of symptoms? Furthermore, and perhaps more insidiously dangerous, is the possibility that individuals avoid genetic testing altogether for fear of opening the door to discrimination; as such, they also miss out on the opportunity to catch and prevent other health issues early on. In short, especially in this age of genetics and preventative medicine, it remains crucial to avoid criminalistion and stigmatisation of men and women who, simply put, need help. People are more than what their methylated DNA may or may not suggest, and to help those who need an extra hand in keeping healthy, society cannot stop seeing them as human.

How Ethical are Stem Cells?

Stem cells have long been thought of as a miracle cure for disease. With their genetic flexibility to become almost any cell, the stem cell has the potential to fix even organs, which have very little potential to recover as they resist self cloning. The article on nature dives into the potential for stem cells in medicine with their regenerative properties, while also confronting the implications of researching with the cells of a potential human life.

Stem Cells

Though there is such a vast market and potential for the stem cell, there are many ethical implications when considering its use. There is much debate over the consent of the woman who's cells are potential subjects and her guarantee of confidentiality when donating the cells. The possible risks of testing with stem cells in medical research, which include the possible formation of tumors and immunological reactions are also touched on in the article.

Gene patent law from a global perspective

Prior to the Association for Molecular Pathology vs Myriad there was an increasing consider that a "storm" of gene patents was coming. This concern was subtantiated by a surge of gene patent applications in the mid 1990s. Gene patent law obviously have implications for parties on both sides of the coin. The requirements stipulated by patents may influence the cost and access that patients have to diagnostic testing. However, the Myriad decisions had broader implications for the protection of intellectual property and how genetic patents are enforced (especially on a global scale). This article reviews the legal nature of gene patents, how they are enforced and how this varies on a global scale. Interestingly, it appears as if the global patent "storm" is very much focused in the USA. Could this be the result of a highly privatized health care system?

Erring on the Side of Sacred

In consideration of the Supreme Court ruling against Myriad, one could possibly anticipate the argument of 'life as sacred' from some religious communities. While this article provides some nuance regarding these communities (for example, suggesting they are not just bible-thumpers blocking progress), it also communicates the need for understanding the intersection between religion and science and the Supreme Court's ruling; is it possible that particular religious ideals and attitudes had a hand in the decisions of the justices? Especially when one considers that a 'naturally-occurring' entity cannot be patented according to the eligibility requirements, how pervasive are these attitudes already?

The Foreshadowed Case

In the aftermath of the Myriad ruling, many claimed that the Supreme Court had little understanding of how genetics actually worked. However, Justice Thomas' opinion should not have been surprising, as another recent case, Bowman v. Monsanto, had dealt with a somewhat similar issue regarding patented genes. In Bowman, the Supreme Court ruled that genetically modified seed could not be intentionally replicated through growth, harvest, and cleaning. This was because Bowman's growth technique constituted a non-natural process, and, therefore, directly recreated patented technology (which is illegal).

However, the Supreme Court very deliberately left out of the Bowman ruling any technologies that might self-replicate without intervention. Myriad was allowed to keep those patents that dealt with so-called non-naturally occurring/edited DNA, because it would have to be intentionally replicated (according to the Court's logic). Neither opinion makes that much sense, especially because DNA and seeds are self-replicating in nature.

Sources

Bowman v. Monsanto and the protection of patented replicative biologic technologies (Science)

For Supreme Court, Monsanto's Win Was More About Patents Than Seeds (NPR)

Bowman v. Monsanto Opinion (SCOTUS)

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Breast and prostate cancers are distinguished from other cancers in that sex hormones are highly involved in cancer development and progression. High levels of these sex hormons has been indicated as major causes for cancer development. A recent study on PNAS has indicated that a special type of tRNA termed SHOT-RNAs, which are small functional RNAs, are abundantly expressed in sex hormone-dependent breast and prostate cancers. Results from this study indicates that there is a direct relationship between enrichment or depletion of sex hormones and SHOT-RNA levels and this is thought to be a useful biomarker and can potentially lead to therapeutic applications.

Gene patents may sound scary but soon they may no longer matter

 There has been a global concern about the issue of gene patenting and several law suites have been under discussions for quite some time now. The United States Supreme Court and the Australian federal courts have dealt with law suites about patenting genes related to breast cancer. A recent article mentions a case of gene patenting raised in Ontario Canada, which focused on the long QT syndrome, a rare disease that is caused by several mutations. As many genes has to be tested altogether in this case, this was bringing more complications to the patenting issues since the owner of the Canadian patent was trying to prevent hospitals from doing some tests. This recent article tells us that advance in technology and new types of diagnostic testing which involve whole genome sequencing and do not require chemically isolated units might help us solve the issues of patenting.