The molecular evolution of genes previously associated with large sizes reveals possible pathways to cetacean gigantism

This discussion includes the size of the blue whale and how they came to be the biggest animals on the planet. The blue whale is actually the largest animal to ever exist in terms of both size and weight, as they can grow up to 100 feet long and weigh up to 190 metric tons. This trend only started occurring relatively recently, only starting about five to ten million years ago. A team from the State University of Campinas in Brazil led by biologist Mariana Nery set out to discover the reasons for the massive growth that the blue whale endured. 

To understand the genetic reasons behind the growth, they compared the DNA of nine different genes across 19 species of whales. When studying genes related to body size, they found evidence of positive natural selection in four genes, some of which are associated with growth hormones and insulin pathways. One unexpected result of this study was discovering that the EGF gene, which stands for epidermal growth factor, turned nonfunctional over time. Despite their enormous size, whales do not seem to suffer from the increased cancer risk that usually comes with having more cells. The study suggests that looking into whale genetics might help identify genes that could possibly slow down the spread of cancer in humans as well.

Gene Therapy for Muscular Dystrophy

 

The FDA has approved a gene therapy for children with muscular dystrophy. This disease is caused by a mutation that rids the body of being able to make a protein it needs for healthy muscle function. Which can lead to potentially fatal health issues if the muscles that control the lungs, heart, etc decay.  The purpose of this gene therapy is to package a protein with this function about one third the size of the original protein and deliver it via a harmless virus to muscle cells. Initial clinical trial results have shown that children have been able to produce the shortened protein with this therapy. However, further clinical trials are needed to confirm if this therapy is actually restoring muscle function. Nevertheless, this  could potentially mean that a treatment for muscular dystrophy is on the horizon. 

The implications of this gene therapy are incredibly profound. If researchers can replicate this therapy for other diseases, think of all of the other ailments that could potentially be cured. Hopefully the future results of these clinical trials prove that muscle function is being restored and muscular dystrophy will be a disease of the past. 

https://www.sciencenews.org/article/first-gene-therapy-muscular-dystrophy-kids

https://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/symptoms-causes/syc-20375388

Why is the first year of a baby's life such a critical period for brain development?

A known risk factor for later cognitive and emotional problems is preterm delivery. However, it has been challenging for researchers to distinguish between inherent brain variations that begin in the womb and the stress of premature delivery, which frequently results in brain damage and oxygen deprivation.

The first concrete proof that the issues begin during pregnancy was supplied by pediatric neuroscientist Moriah Thomason study.Her team's brain imaging of preemies revealed that compared to fetuses who were carried to term, the brain activity of the preemies-to-be demonstrated decreased connection between multiple brain regions. 

Most notably, the researchers discovered changed neural connections in networks, including a language center on the left side of the brain, that eventually support language. More proof of prenatal brain damage in preemies has now been discovered by researchers. For instance, a different team discovered in 2021 that 24 infants who were delivered early had smaller brain sizes and less CSF fluid while still inside the womb when compared to a group of infants who were carried to term. And numerous investigations have discovered that the amniotic fluid and placental tissues of women who delivered early had significant levels of inflammation brought on by bacterial or viral infections.

Gene-Editing Tools Pave Way for New Alzheimer's Treatments

Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR, is a potent technique that enables precise gene modification. The research discussed centers on identifying individual genes linked to Alzheimer's disease in an effort to lower risk or decrease the illness's course.

Amyloid precursor protein (APP), which is essential for Alzheimer's disease: Depending on how it is broken down in the brain, the APP can produce metabolites that are either protective or pathogenic. In order to decrease the creation of beta-amyloid plaques, which are harmful protein deposits linked to Alzheimer's disease, while improving neuroprotective activities, the researchers employed CRISPR to alter the APP gene. In an Alzheimer's disease animal model, the CRISPR therapy resulted in a decrease in beta-amyloid plaques and related signs of brain inflammation as well as an increase in neuroprotective APP molecules. 

The APOE-e4 gene, which is regarded as a prevalent risk gene for Alzheimer's, is the focal point of the additional investigation. Having two copies of APOE-e4 raises risk of Alzheimer's disease by up to 12 times, whereas inheriting one copy increases risk by two to three times. In humanized mouse models and small brains made from Alzheimer's patients, the study demonstrated that levels of APOE-e4 may be greatly lowered using CRISPR without altering levels of other APOE variations that are thought to be neutral or protective. This strategy has the potential to help cure or stop Alzheimer's disease.

Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is a rare genetic disorder that 9 out of 10 times causes obesity. It is rare because it is autosomal recessive, so both parents have to carry the recessive gene for a 25% chance their child could have BBS. More than 20 genes have been found to be associated with BBS. Only about 2500 people in the United States have BBS. A parent of a child with BBS explained how their child would eat so much, and sneak food so often that they had to put locks on their cabinets and fridge to keep their child out. It is a struggle because hunger is sometimes all that victims can think about, but the urge never goes away. Common symptoms across those with BBS include obesity (typically by age 5), hyperphagia, visual impairments, postaxial polydactyly, renal anomalies, diabetes, cognitive impairments, and more. The pathway that regulates hunger, satiety, and energy spent is the MC4R pathway. The pathway is activated by leptin, a neuro-signaling hormone from the adipose tissue. BBS genes help guide leptin to the POMC neurons, and without it, hunger, satiety, and energy cannot be controlled. Diet and exercise are not usually enough to treat BBS. IMCIVREE is a prescription medicine for people ages 6 years and older with obesity due to BBS. It helps them lose weight and keep weight off. Side effects of IMCIVREE include male and female sexual function problems. depression and suicidal thoughts, darkening moles, and benzyl alcohol toxicity.

The Evolution of the Human Skeleton from Great Apes

From years of research on the evolution of the human skeleton, scientists have noticed that our skeleton is similar to apes. Even our ancestors' physical features resembled apes like their jaw. Researchers now have more advanced instruments to dive deeper into understanding human genetics and compare it to great apes. At the UK Biobank scientists used artificial intelligence to access 30,000 human skeleton X-rays so they could research why some humans have degenerative joint diseases like arthritis, and its connection to apes. They measured different parts of the human skeleton and found different lengths of certain bones were linked to arthritis in the back, hips, and knees. In many cases, there was a linkage of bone lengths in families. Apes were less likely to have arthritis because they walked on all 4 limbs compared to humans who started waking bipedally. Our form changed, but the bones kept their shape, and some families are suffering the consequences.

Advances in Detecting Mitochondrial Diseases and Cures

Previously, mitochondrial diseases were said to be rare because not many people were diagnosed with one. Although with new genetics research, scientists are realizing that mitochondrial diseases are not as rare as they previously thought because they would misdiagnose patients with other diseases. Mitochondrial diseases will injure your cells, knocking out entire organs and eventually leading to death because the mitochondrial struggles to send enough energy/signals to the rest of the cell to be detected in genetic tests. Linlin Zhao, an assistant professor of chemistry at UC Riverside, studied that the TFAM protein could repair or remove damaged pieces of DNA molecules. This is a great step in being able to cure mitochondrial diseases. TFAM is the mitochondrial transcription factor A which is a mtDNA binding protein that maintains genes. New research shows that decreased mtDNA is linked with aging-related hypotheses which is a start to understanding how TFAM abundance and disease are linked. Zhao and his colleagues were not only surprised by TFAM since is known for its different functions, but they also took a step in helping repair cells that mitochondrial diseases damage. With future research, mitochondrial diseases may be easily detected and cured.

Human Embryo Models From Stem Cells

 

This picture of an embryo model from Jacob Hanna's lab in Israel is one of the few closest lab-grown embryo models to ever exist. These models come from stem cells and are the closest looking cells to early embryonic development because of their possible yolk sac, formation and shapes of cells, and possible placental-like cells. With this advancing technology, scientists begin to question how far they could grow an embryo in a lab. Depending on your country, there are regulations to determine if a scientist could even attempt to achieve a lab-grown human embryo. 

There is a lot of controversy on whether embryo-like structures are useful for real research or are just being used like a game of how far one can one grow the model. Embryo models represent post-implantation stages of embryonic development. During this very early stage of pregnancy is when many pregnancies fail. Researching a human embryo model could teach scientists a lot about why these failures and developmental disorders happen and guide researchers in how to fix them. Although, if this technology gets into the wrong hands, children could be born without a sperm or egg which groups with opinions on cloning. 

A study proposes that the genetic sequencing of infants should be conducted at birth.

The BabySeq Project was a randomized clinical trial designed to measure the utility of using genomic sequencing in routine newborn care. Several years ago, they conducted research which revealed that 17 of 159 seemingly healthy babies whose genes were sequenced showed mutations that revealed the likelihood of future illnesses. There is a follow-up that BabySeq did, which shows that three mothers from the previous study took action to prevent the conditions that they saw mutations for. 

Currently, at birth, newborns are screened for 60 diseases, but there are 700 treatable conditions that are not included in the screenings. The possibilities with these technologies could potentially identify biomarkers that develop diseases, which could help with preventative measures. In terms of what BabySeq’s impact is on the modern family, three of the babies were revealed to be carrying BRCA1 and BRCA2 genes, which can cause an increased risk of cancer. Their mothers, who did not know they were carrying this gene, had risk-reducing surgery after learning of their baby's status.

Fyodor Urnov, an expert in gene editing at the University of California, Berkeley, argues that it is unethical to not use this technology, considering it can save lives long term. In my view, assessing this technology on a case-by-case basis is essential, as it may prove particularly valuable for families with a background of genetic illnesses. However, a significant portion of our population remains reluctant to embrace the concept of DNA collection and sequencing. In my opinion, DNA sequencing at birth should be an option for parents, but never forced or pressured to those who are disinclined. 

The Simplest Animal with Accelerated DNA Repair in The Presence of Ionizing Radiation

    Cancer affects millions of people across the world and available treatments can only do so much to mediate symptoms and stall its progression. However, there is a multicellular organism that has shown to successfully maneuver cell damage and there is no recorded observation of these simple animals overly affected by cancer due to their reparative mechanisms. The Trichoplax adhaerens reproduces asexually, which may have you think its species would be more susceptible to cancer than humans yet that has not been the case. In this study, the expression of reparative genes and those that incite apoptosis have shown to increase with exposure to radiation. Although exposure has caused morphological change in the organism, it is able to extrude these mutations from its body. 

    The transcriptome analysis compared gene expression at difference rates of radiation exposure. Among the genes analyzed were those that share functional characteristics to human genes, which act as tumor suppressors and function in DNA repair. Some ortholog genes are not well known in humans, yet the study suggests that one in particular, EMC2, functions in response to cell damage. The study states that, "The function of EMC2 is not well known in humans, but our results suggest that at least one of its functions may be X-ray damage response." Studying T. adhaerens' resistance could aid in identifying genes that act in DNA repair and apoptosis in humans given the orthologous genes present. How cancer treatments are conducted could improve and/or could be supplemented by further analysis of T. adhaerens.

Is the Absence of the Y Chromosome Accelerating Cancer Progression in Males?

A new study from Cedars-Sinai Medical Center is showing the loss of the Y chromosome assists cancer cells in avoiding detection by the body's immune system. Aging men can lose the Y chromosome during cell division. In some older men, more than 4 out of 5 white blood cells lack a Y chromosome. Loss of the Y chromosome is shown to be heavily associated with several diseases and cancers in aging men. 

The Ceders-Sinai Medical Center concluded that tumors that lack the Y chromosome grow at a much faster rate and are more aggressive, but are also more vulnerable to immune checkpoint inhibitors. This knowledge could provide an explanation as to certain cancers are worse in men than women. It can also help physicians with treatment pathways and help with the research for alternative tumor treatment.  

For example, T-cell exhaustion is a condition in which T cells lose their ability to kill certain cells, weakening the immune system's fight against cancers and other diseases. If we understood the genetic connection between losing the Y chromosome and T-cell exhaustion, we could potentially find a way to prevent it from occurring altogether. 

Pangenome: The New Genetically Diverse Human Genome

The previous human genome reference was released over 20 years ago. The new human genome, called "pangenome," takes into account several genetic references from a much more diverse set of individuals than the previous, of which includes only a few dozen individuals yet the base of the DNA was of one man from Buffalo. Compared to the new human genome reference it lacks the variability of the humans at large. Pangenome has filled in the missing pieces of the last reference, 120 million to be exact and captures the 47 individual's genetic sequences, which includes those of African American and South American descent to name of few. To better understand the complexity of the new reference the New York Times article, Scientists Unveil a More Diverse Human Genome, by Elie Dolgin, emphasizes the genetic diversity of the reference by comparing it a corn maze. Each color in the picture references a possible route and include yellow for duplication, pink as inversion, deletion being green and blue, and insertion is light blue.

Having a diverse representation of not only the human genome, but how diseases may present itself differently among people is necessary in order to provide the best care possible to patients. This article reminded me of how often skin conditions appear in light versus in darker skin and how these conditions are largely represented by white skin in textbooks. For genomes to come from a wide range of individuals regarding ethnicities and locations, then come together to form a overall human genomic reference would provide a more accurate representation of human's genetic makeup with capability of better addressing genetic diseases. 

Sea Turtle genes could help them adapt to a changing environment.

The genetic foundations of sea turtles that enable them to thrive in oceans are something that scientists have yet to figure out. A team of researchers at the University of Massachusetts Amherst revealed surprises in the genetic map that might show us the key to how turtles will survive in our rapidly changing ocean—and why some species may not. 

The researchers used a new technique, long-read sequencing, which made it possible to sequence genomes accurately from any living species. The sea turtle genomes were sequenced, and the results were surprising. Green and Leatherback turtles have incredibly similar genomes and share a common ancestor from about 60 million years ago. The differences in their genomes were found in the micro-chromosomes and affect immunity. Green turtles evolved more genes, which were dedicated to immunity. This development is key for the longevity of the species, as they are better prepared for the changes in their oceans. The Leatherback turtles also show lower genetic diversity, which is not favorable for evolution, because, despite their resilience thus far, they may not be able to evolve with the harsh environments caused by human activity. Conservation biologists, with this knowledge, are able to make more informed decisions based on the animals at higher risk of extinction genetically.

Virtual Microbe with the Potential of Advancing Research

   The discovery of Escherichia coli in 1885 has been followed by a vast collection of studies on the bacteria due to its ability to maintain in laboratories making it suitable for research. This made it possible for scientists to eventually discover how to produce insulin by way of its biochemical processes. Given the vast information discovered about E. coli, such as how its genes function together, how inserted DNA can alter its genetic functions, and teaming with scientists to better capture its behaviors and how removing genes may alter its growth, Michael Ellison seeks to model its genetic makeup virtually. The creation of the International Escherichia Coli Alliance in 2002 enabled for numerous laboratories to work on the same project. As stated by Carl Zimmer in New York Times, Building a Virtual Microbe, Gene by Gene by Gene, the bacterium is estimated to encase millions of biological molecules. Being able to synthesize various strains of E. coli with a distinct difference in its genome, a different gene is removed in each strain, can improve understanding a gene's role in carrying out functions, as was mentioned in the article. By gathering the information gained from working with scientists across the world on these strains increases the database that could be utilized by Dr. Ellison and his colleagues construct a virtual microbe. 

    The plan for Project Gemini is to track each individual molecule within the E. coli and has begun with a membrane that resembles how a molecule would behave in real life. To eventually get to a point where not only with sufficient data can a biochemically accurate microbe be reconstructed, but to adapt the program to visualize human cells could accelerate research in drugs and improve our understanding of illnesses. The comments by Dr. Ellison involving the need for an advancement in computers and simply the complexity of E. coli being difficult to simulate on existing programs makes me doubt a fully constructed and functioning model would be ready within the next decade. But I do agree that the use of technology to emulate cellular functions would be of great benefit to researchers as live samples in controlled settings can still be contaminated, interrupting procedures. 

New Genomic Techniques can make agricultural production more sustainable

NGTs (New Genomic Techniques), are methods for creating targeted mutations in the genome of living organisms. An example is CRISPR/Cas9, which allows for precise editing of DNA on the level of individual units of genetic code. The precise editing by NGTs allows for rapid results over traditional methods, which can be useful considering that plant diseases are spreading due to climate change. The difference between a GMO and an NGT is that the makeup of a GMO has been modified using biotechnology to create a desirable product. NGTs do not have any foreign genetic material, just an edited version of their original genome.

A few examples of plants produced using NGTs are salt-tolerant rice varieties and virus-resistant cassava. NGT crops can increase yield and reduce the need for harmful insecticides, which would increase sustainability in agriculture overall. There is precariousness around the idea of releasing new genetic traits into nature. The unknown effects that NGT has on wild crops. Some may be more welcome to NGTs, because the mutations like this occur naturally, unlike GMOs. Many countries are treating them differently as well when it comes to regulations. In my opinion, with a rapidly growing population, we have to start introducing these biotechnological methods to feed everyone on our planet.

The study of how genetics shapes society.

Robbie Wedow is an assistant professor and data scientist in the College of Liberal Arts at Purdue University. He uses genetic databases to study the interaction of genetic and social forces with the environment. According to Wedow, it is important to understand that these genes have absolutely no control over a person’s life or future. Each SNP (single nucleotide polymorphism) has little effect on broader outcomes, such as educational attainment. The goal is to use a genetic approach to gain a better understanding of the complexity of human behavior. “Sociogenomics isn’t necessarily about biology, like some might think,” Wedow said. “When someone studies cancer genetics, they are studying it because they want to elucidate the biology of cancer; they want to figure out ways to better diagnose it, track it, and treat it. But researchers in the field of sociogenomics want to study genetics in order to do better social science. No one would ever study sociology without considering socioeconomic status and environment. We want to be able to take genetics into account in the same way."

But how will utilizing genetics help the field of sociology? Wedow and co-author Andrea Ganna of the University of Helsinki conducted a study that examined 109 survey questions to find out how people’s genes related to their responses. This addresses a longstanding challenge faced by the field of sociology, providing valuable insights that have eluded researchers for many years.