Honorable Mention Excerpts

 

 

 

Daria Beatini

Bergen County Academies

Teaher: Judith Pinto

 

Richard Robert’s and Phil Sharp’s discovery of introns in 1977 entirely changed the 1969 definition of a gene by disproving the earlier notion that a gene was a continuous segment of protein coding genetic material, as introns do not play a direct role in protein coding. . . . .

 

 . . . On the TPH1 gene there is a single nucleotide polymorphism, A218C, located on intron 7, and studies have shown that this polymorphism is associated with manic-depressive illness, as it is located in a potential transcription-factor binding site and therefore could affect TPH1 gene expression (1). Given that the TPH1 gene aids in the synthesis of serotonin and a polymorphism on one of its introns could potentially lessen the gene expression due to its location, there is a strong correlation between serotonin dependent mental disorders and the regulatory effects of an intron. This shows the extent to which the intron and its functions change the 1969 definition of a gene, given that non-coding sections of DNA not only exist, but also play a large role in gene regulation. . . . .

 

 . . .  The existence of introns as a whole as well as their regulatory effects extends the original definition of a gene far beyond its bounds. The discovery of introns as well as subsequent discoveries about their function and purpose has added to the wealth of knowledge regarding the human genome, and additionally, offers explanation in respect to different diseases, the ability of transcription factors to reach a gene, and how the cell cycle is regulated.

 

 

Jennifer Chen

Winston Churchill High School

Teacher: Anat Schwartz
 

The plasticity of splicing allows for various mature transcripts and disparate protein isoforms to be produced from just one gene; this phenomenon is referred to as AS (Keren et al., 2010). General modes of alternative splicing (AS) include exon skipping, alternative 5’ splice site and 3’ splice site selection, intron retention, and mutually exclusive exons. AS enhances the traditional definition of ‘gene’ by clarifying that one gene has the ability to code for multiple protein products

 

Around 94% of human genes contain alternative splicing, suggesting the comprehensive and crucial nature of the phenomenon (Oltean and Bates, 2014). . .

 

. . . a recent breakthrough discovery of a novel, naturally occurring, p53 splice isoform (p53Ψ) enforces the importance of alternative splice site AS (Senturk et al., 2014). Encoded by TP53, full-length p53 is a well-characterized tumor-suppressor that promotes cell cycle arrest and apoptosis. However, an alternative 3’ splice site in TP53 intron 6 generates p53Ψ, which lacks features such as DNA binding and transcription activity that exist in the full-length p53. Even with these missing features, p53Ψ can reprogram cells to acquire metastatic features through the regulation of cyclophilin D activity, thus promoting – rather than suppressing – tumorigenesis. . .

 

. . . AS is an elementary, essential, and extraordinary mechanism present in the majority of human multi-exon genes. The impact of AS on human physiological and pathological processes is slowly gaining recognition, but many aspects of AS remain unexplored. With the recent advances in high-throughput sequencing technologies and improved splicing sensitive microarrays, I am confident that splice variants, AS’s crucial functions and splicing regulatory networks will continue to be unveiled.

 

Arthur Dennis

Bergen County Academies

Teacher: Judith Pinto

 

In 1977, two scientists independently made a discovery that would overturn several leading notions in the field of gene expression: RNA splicing. American molecular biologist Philip Sharp and English molecular chemist Richard Roberts simultaneously observed a single mRNA molecule hybridizing into more than one stretch of DNA, contradicting Crick’s notion of colinearity (1; 2). Roberts and Sharp further noted that during protein synthesis the supposed continuous genetic material sometimes breaks apart and re-attaches itself to other pieces (1; 2). This process, now labeled RNA splicing, is predicated on the existence of exons and introns, both directly contradicting the now clearly falsifiable belief that genes are discrete, contiguous segments of DNA. . .

 

. . . some introns possess the ability to self-splice (3). One such example, Group II introns, are found in mitochondrial genes and exhibit an intron excision process not unlike that found in pre-messenger RNA splicing (3). Over two decades later, a group of scientists identified the U6 catalytic metal ligand snRNP as the catalyst for the splicing, which corresponds with the catalytic metal structures on group II introns. Their findings suggest that group II introns and spliceosomes share catalytic mechanisms and perhaps evolutionary backgrounds (4). . .

 

. . . current research attesting to RNA splicing’s role in abnormal mRNA transcription provide vital information to cellular cancer development, and further research on group II intron’s structure aid in suggesting the evolutionary purpose of introns (10). Forty years ago, RNA splicing contradicted existing theories and forced the scientific community to re-examine their assumptions; now, it lies at the backbone of describing the human genome and its processes and forces the scientific community to further examine and fully understand it.


Alex Dent

James Madison Memorial High School

Teacher: Cindy Kellor
 

Through alternative splicing (AS), genes are now understood to be more versatile than previously thought. However, the versatile nature that AS lends to genes also comes with a price; one mutation in DNA can disrupt the function of multiple gene products. Unsurprisingly, AS has been linked to many human diseases. Many of these diseases are neurological in nature because of the prevalence of alternatively spliced products within the nervous system. . .

 

. . . In 1969, one would have predicted the the genome and proteome would be closely aligned. However, the discovery of alternative splicing demonstrated that this is not the case. Today, we better understand and continue to research the intricacies of translating the genome into the proteome, which could lead to greater understanding of the mechanisms of certain diseases.


Thomas Ferrante

Bergen County Academies

Teacher: Judith Pinto
 

DNA. RNA. Protein. For years these three words served as an infallible explanation of gene expression. The concept was so vital to the understanding of DNA present at the time that it was called the central dogma of molecular biology. But as with many theories, exceptions were soon discovered. . .

 

. . . The discovery of microRNA (miRNA) revealed a process that forever changed the definition of a gene, revealing the existence of DNA that coded for a new type of RNA that was never meant to become a protein, and even prevented the translation of other RNA. miRNA expands the definition of a gene by redefining the final product of gene expression and demonstrating a unique method of post-transcriptional gene regulation. . .

 

. . . Since the first miRNA was discovered in 1993 in C. elegans, thousands of miRNAs have been identified in the human genome (5). Many miRNAs are not yet understood, but their significance has already been demonstrated. miRNAs have important roles in cardiovascular disease, neurodevelopmental diseases, and even cancer (3). . .

 

. . . miRNA extends the definition of a gene by showing that not all genes code for proteins, and that the final product of gene expression can be RNA. Even more amazing is that genes that do not code for proteins can be used to regulate the expression of other genes. Sequences once thought to be “junk DNA” may have pivotal roles in countless diseases.

 

Isabella Li

East Chapel Hill High School
Teacher: Patricia Berge

 

Modern genetics is based upon the idea of the “central dogma” described by Francis Crick in 1956: the flow of genetic information goes from DNA to RNA to protein. By this traditional view, genes exist solely to code for protein, and RNA is simply an intermediate between genes and proteins. Recent research, however, tells us that this picture is far from complete. For example, in the past twenty years scientists have discovered regulatory noncoding RNAs (ncRNAs) such as piwi-interacting RNAs, microRNAs, and long-noncoding RNAs that do not participate as intermediates between genes and proteins, yet, through various mechanisms, have great effects on gene expression. . .

 

. . . Another small noncoding RNAi species, microRNA (miRNA), is around 22 nucleotides long and regulates expression of endogenous genetic information. miRNA-encoding genes lie in the introns and intergenic regions of DNA, encompassing an estimated 1.5% of the human genome (MacFarlane & Murphy, 2010). . .

 

. . . Genetics does not exist as a simple pathway; it is more than the central dogma of gene to RNA to protein. Genes do not have to code for protein, and understanding their other products such as regulatory noncoding RNA gives us new insight into fundamental biology—what allows our bodies to function properly, and with that, what causes our bodies to malfunction.

 

Rick Li
Naperville Central High School

Teacher: Nicholas DiGiovanni

 

In 1983, Barbra McClintock won the Nobel Prize for discovering that segments of DNA, called transposons, are able to move to different parts of the chromosome. Furthermore, they do not directly make protein products, but instead regulate other genes. The existence of these movable cards in a shuffling genetic deck paints genes as more fluid, complex structures than they were once perceived to be.


The transposon defies the prevailing view of the gene. These snippets of code are shorter than protein-coding genes. They are repetitive, not distinct, living in abundance along the chromosome. Unlike traditional genes, transposable elements do not code for one specific protein product. Instead, facilitated by RNA and DNA, they sever themselves from their natural locations and inject themselves into new regions, leaving both damaging mutations and important improvements in their wake. . . .

 

. . . Introducing a transposon within a gene can cause vast differences in its effect. The angiotensin-converting enzyme causes blood vessels to narrow and is coded by the ACE gene, which comes in two different variants. When the gene has no transposable element present, it is known as ACE-D. In this case, blood vessels can constrict normally. Occasionally, however, an Alu element will relocate itself into the ACE gene, transforming the ACE gene. The variant that contains the insertion of an Alu element is known as ACE-I, and the transposon-altered gene changes the enzyme. The new proteins dilate blood vessels, take in oxygen, and increase muscle mass, giving the body the ability to engage in sustained cardiovascular exercise, such as distance running (Jamshidi et al). . .

 

. . . Whereas many genes produce proteins useful for the body, transposons produce RNA designed to suppress products. Scattered around the genome, these pockets of genetic code have developed methods of controlling themselves, ensuring their continued presence and success in the genetic code.

 

Sarah Link

Eureka High School

Teacher: Lindsey Mueller

 

In 2001, the Human Genome Project determined that in the human genome, the 21,000 genes that code for proteins make up only 2% of the human genome (Park 2012). The other 98% was considered “junk” DNA. In other words, nobody really knew what its function was. Today, we know that the majority of this “junk” DNA does serve a purpose. However, its function is not necessarily to produce proteins as the traditional definition of a gene suggests. . .

 

. . . In females, there are two copies of the X chromosome in each cell. However, only one copy is active. The other copy is inactive and forms a Barr body in the cell’s nucleus. Located on the q arm of the X chromosome, Xist does not code for a protein but rather stays in the nucleus of the cell and coats the inactive X chromosome, aiding in the formation of the Barr body. . .

 

. . . Whether they regulate genes on another chromosome, imprint an allele, or inactivate a whole chromosome, lncRNAS are genes that don’t code for proteins but are still a necessary part of the genome.

 

Paul Slaughter
James Madison Memorial High School

Teacher: Cindy Kellor
 

In 1977, Richard Roberts and Phillip Sharp independently determined that eukaryotic genes were not continuous, but instead contained many interruptions (The Nobel Foundation). They noticed that every time mRNA transcribed a strand of DNA, the mRNA was shorter than the DNA strand it had copied. They eventually realized that the mRNA was shorter because it did not include stretches of DNA now known as introns. . .

 

. . . A promoter is a sequence of DNA that serves as an on/off switch for genes (Leja). These types of switches control, for example, when in their lives men can grow a beard or go bald. Promoters also are responsible for why different kinds of cells make different kinds of proteins. . .

 

. . . Telomeres are yet another example of noncoding DNA found in the human genome. They are located on the tips of each chromosome and are especially important during DNA replication. When this occurs, the outer ends of the telomeres are lopped off through a process known as nucleolytic degradation. Telomeres serve as buffers that protect coding DNA from being lost during replication. If any exons were shortened during replication, imperfect copies would be created that might produce harmful proteins or fail to make necessary ones (Shammas 28, 29). . .

 

. . .The bulk of our genome, in the form of noncoding DNA, is instead involved with regulating, decoding, and managing our genetic information in ways we are only beginning to understand.

 

Dennis Yatunin
Stuyvesant High School
Teacher: Maria Nedwidek-Moore

 

While at first scientists believed that genes only encode proteins, the mapping of the human genome showed that only around 2% of our DNA codes for proteins. This shocking discovery led us to wonder what exactly the rest of our DNA does. Recently, the Encyclopedia of DNA Elements (Encode) project showed that around one fifth of the human genome consists of genes that, rather than encode proteins per se, provide ways to regulate the creation of proteins [Jha, 2012]. . .

. . . Retrotransposons make up nearly half of the human genome, and they exploit cells in order to survive and proliferate. They pose a constant threat to humans, as, if they insert themselves into genes that encode functional proteins, they can disable those genes or activate them when they are not needed. . .

 

. . . The silencing of certain genes after they have already been transcribed is an incredibly important process in humans. Were it not for fine-tuned processes like RNA interference, we would be no more complex than the simplest organisms on Earth.