David Shenk describes on page 24 how "most genes cannot be counted on to directly produce specific traits, They are active participants in the developmental process and are built for flexibility" (Shenk 24) and goes on to describe how some phenotypes like hair color and eye color are near Mendelian, but still succumb to gene-environment interactions. This description aligns itself to alternative splicing in how one gene, passed down from a parent, can code for a specific protein while another gene, using different exons and introns of the same sequence, can code for an entirely different protein. Describe how this flexibility in genes relates to the phenotype of a person and its near Mendelian results in many physical traits while also acknowledged how there can be deviations of what should happen, due to alternative splicing, in the passing down of a completely Mendelian trait. Use information from Campbell in chapter 17 and 18 of alternative splicing and chapter 14 of inheritance.\
-Kyle Nelson (kynels21@gmail.com)
Gene expression is facilitated by alternative splicing, because the environment stimulates the splicing of different introns and exons, causing different proteins to be translated, and thus causing different gene expression. Thus, alternative splicing provides gene expression with incredible flexibility, allowing for myriad combinations of introns and exons to be spliced, leading to many different types of proteins. However, "a simple Mendel-like result doesn't mean that there wasn't gene-environment interaction" (Shenk 24), but instead some traits appear Mendelian simply because the organisms exhibiting those traits are living in the exact same environment as their parents did. Furthermore, epigenetic inheritance lends to this seemingly Mendelian inheritance, as the same epigenetic material causes children to have the same phenotypes as the parent. Epigenetic inheritance can modify chromatin structure to result in a new phenotype in the child despite genetic inheritance (Campbell 358), or could also be the reason for the apparent Mendelian inheritance.
ReplyDeleteTherefore, due to environmental factors, gene expression is clearly impacted by alternative splicing and their effect on translation for proteins. Alternative splicing allows relatively few genes to make many polypeptides (Campbell 336). This also means that there are many different possible variations in gene expression, as there are many possible proteins to create for the many different possible forms of gene expression. Alternative splicing creates the flexibility that allows the environment to change a person's phenotype, such as someone changing from brown to hazel times over time. Alternative splicing also means that traits can no longer be called completely Mendelian. With so many possible proteins per gene, gene expression is always a product of the environment, as any small change in environment can change the proteins translated for. Rather, apparent Mendelian inheritance results from continuity of environment from parent to child. According to a study conducted by the Departments of Stress Science of the University of Tokushima Graduate School, environmental factors, in this case stress, can change alternative splicing of genes. According to the study, stress on medical students caused their body to skip splicing 6 exons out of 27 regularly spliced exons. This change in splicing, of course, impacts gene expression, as different proteins are produced by the differently spliced gene. Thus environmental impact on alternative splicing also has an important effect on gene expression.
This relates to the biological theme of continuity and change, because environmental and epigenetic factors cause both continuity and change in the phenotypes of parents to the phenotypes of the children. The theme of continuity and change means that although some biological factors stay the same, such as phenotypes through inheritance, other factors must change, such as changes in phenotype due to environmental changes, which allows for evolution to occur. Alternative splicing is really an agent of change within gene expression, as alternative splicing impacts the way a gene can be expressed by changing the proteins translated for. However, when environmental and epigenetic factors stay the same, thus keeping alternative splicing constant, gene expression and phenotype tend to continue from parent to child. When environment and epigenetics change, gene expression usually does the same.
Aaron Zalewski (bitquest@yahoo.com)
Alternative splicing is post transcriptional processing of a pre-mRNA in which introns are excised from the RNA strand and exons are spliced together. Alternative splicing allows for multiple “different protein products” from one gene (Campbell 336). Because of this, dominant Mendelian traits, such as eye color, are not always passed on from parent to offspring, as in the case that Shenk cites in which “’two blue-eyed parents can produce children with brown eyes,’” (24). Because of the ability of alternative splicing to combine different RNA sequences, gene sequences that might be expected to produce one trait (e.g. blue eyes), may be excised and the exons that are spliced together to be excised would become expressed. Ultimately, a spliceosome complex and the flexibility of pre-mRNA in terms of its introns and exons contribute to why Mendelian traits aren’t always expressed as they are expected to be.
ReplyDeleteFurthermore, recent scientific evidence suggests that chemical modifications to pre-mRNA also impacts alternative splicing and gene expression. Because “histone modifications can cause splice site switching,” the proper introns are not always excised, causing different sequences of RNA to be translated into proteins, which affects gene expression (Luco http://www.sciencemag.org/content/327/5968/996.short). Histone modifications to pre-mRNA thus further contribute to the flexibility of genes and how Mendelian traits are sometimes not passed down to offspring.
In the context of evolution, alternative splicing and the variability of gene expression reinforce Shenk’s GxE model and exhibit the potential limitations of our inherited genes. Although natural selection favors certain genes, a suitable environment is required to ensure that such genes are expressed and not excised during alternative splicing. Furthermore, the flexibility of genes after RNA transcription challenges the deep-rooted belief of Mendelian inheritance, and points to other environmental factors, such as histone modification, beyond the scope of DNA that affect ostensibly inherited traits.
David Ribot (ribotdavid@gmail.com)
The Argument: As Shenk emphasizes as a constant theme of his research, genes are not a conclusive determinant of the phenotypes exhibited by an individual. Instead, it is the interactions between genes and the environment that determine the phenotypic traits that organisms express. However, another crucial component that can alter gene expression significantly exists in the form of alternative RNA splicing, in which many genes can be transcribed and translated into multiple polypeptides, depending on which segments of the pre-mRNA are processed as exons during RNA processing (Campbell 336). According to a study published by the Public Library of Science, the process is regulated by the binding of general splicing factors (enzymatic proteins) to pre-mRNA during the formation of a spliceosome (http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0030406). Thus, the number of proteins produced by an organism has the capability to be much greater that the number of genes in its genome.
ReplyDeleteThis flexibility in gene expression (transcription, processing, and translation) via alternative RNA splicing allows for the (relatively slight) possibility of exhibition of phenotypes different than what would be predicted using Mendelian genetics. Even in the case that rudimentary Mendelian genetics do predict various phenotypes of the offspring (as is often the case), that does not mean that genes are the sole determinant of such physical traits. As Shenk explains, “A simple Mendel-like result doesn’t mean that there wasn’t gene-environment interaction” (24), only that the interaction of genes and the environment produced the same phenotype as what would be predicted using Mendelian genetics. Another factor that can contribute to departure from traditional Mendelian inheritance is epigenetic inheritance. By altering the physical structure of the chromatin via histone acetylation and DNA methylation, alternative phenotypes could be exhibited by offspring despite what genetic sequences were inherited. As an example, “’two blue-eyed parents can produce children with brown eyes.’ Recessive genes cannot explain such an event; gene-environment interaction can” (24). In addition, alternative RNA splicing and epigenetic inheritance can also explain such a phenotypic occurrence.
As Aaron explained, the concept of alternative RNA splicing relates to the biological theme of continuity and change. While several phenotypes of a species remain constant over time (the continuity), variation in external stimuli and epigenetic inheritance can lead to differences in gene expression and varying phenotypes (the change).
Nick Sotos (nsotos13@gmail.com)