Genome complexity: how so few genes make us so complex (Introduction)

by David Turell @, Wednesday, January 15, 2020, 19:40 (204 days ago) @ David Turell

The human genome is small when the number of genes is measured, but those genes can mix and match code to produce many results from the same gene:

"Thanks to the advancement of large-scale proteomic studies over the decade following that milestone, researchers realized that some human cells contain billions of different polypeptides. Researchers realized that each gene can encode an array of proteins. The process of alternative splicing, allows a cell to generate different RNAs, and ultimately different proteins, from the same has become clear that alternative splicing is common and that the phenomenon helps explain how limited numbers of genes can encode organisms of staggering complexity. While fewer than 40 percent of the genes in a fruit fly undergo alternative splicing, more than 90 percent of genes are alternatively spliced in humans. (my bold)

"Astoundingly, some genes can be alternatively spliced to generate up to 38,000 different transcript isoforms, and each of the proteins they produce has a unique function. Like the chapters of a book, coding segments of the genome, known as exons, appear in series, and alternative splicing works by including or leaving out some of these genomic passages. Some chapters are required—that is, they are found in every transcript—and some are optional, so-called alternative exons. The differential splicing of these regions from an RNA transcript creates customized and condensed genetic messages. Molecular editors control the complicated flurry of exon selection by recognizing the chapters needed for a given protein and discarding the others. The final arrangement of exons in a spliced RNA molecule shapes the resulting protein’s structure and function.


"(ENCODE) project was launched to identify the functional elements in the human genome, and the effort ignited controversies as to whether introns were genetic “junk” that the cell invested precious energy and resources to transcribe only to trash prior to translation. Alternative splicing gave these seemingly nonfunctional elements an essential role in gene expression, as evidence emerged over the next few years that there are sequences housed within introns that can help or hinder splicing activity. These enhancer and silencer sequences are recognized by RNA-binding proteins (RBPs) whose presence affects spliceosome docking and assembly. RBPs allow exons or portions of exons to be combined or skipped in unique patterns, such that a single transcript can be spliced into several possible mature mRNA isoforms, or splice variants, each translated into proteins with potentially diverse functions. (my bold)


"Each splicing event requires three components: the splice donor, a GU nucleotide sequence at one end of the intron; a splice acceptor, an AG nucleotide sequence at the opposite end; and a branch point, an A approximately 20–40 nucleotides away from the splice acceptor. These three “splice sites” are recognized by two core small nuclear RNAs (snRNAs) of the spliceosome, U1 and U2, followed by a protein, U2AF. The binding of these molecules to a transcript recruits a complex of three more snRNAs—U4, U5, and U6—which facilitates the splicing reaction.

"A variety of factors affect how transcripts from a particular gene are spliced. Exon recognition by the spliceosome can be influenced by RNA binding proteins (RBPs), which bind to enhancer and silencer motifs within the mRNA and help or hinder spliceosome recognition of the splice sites. And because pre-mRNAs are frequently spliced as they’re transcribed, the speed of transcription by RNA polymerase II further tunes the window of opportunity for splice site recognition by the spliceosome.


" their studies revealed that every tissue in the body is characterized by a unique set of splicing events...They found that brain, heart, and skeletal muscle present with the most highly conserved and tissue-specific alternative splicing patterns, further underscoring the functional importance of tissue-specific alternative splicing.


" Giudice, found that numerous differentially spliced genes encode proteins involved in intracellular trafficking, and these splicing events are controlled by two RBPs: CELF and MBNL. All signs pointed to a splicing network. Follow-up work revealed that the expression levels of CELF and MBNL are inversely tied to one another during muscle development, and that they antagonistically regulate more than 1,000 pre-mRNA transcripts, some of which are translated into proteins critical for muscle contraction.


"Researchers are also exploring the possibility that chromatin architecture and epigenetics serve as another layer of splicing regulation by modulating the rate of RNAPII transcription."

Comment: Junk DNA is gone. The complexity of the human genome is only partially unraveled and what is revealed so far is an irreducible complex system that MUST be the result of design. It is highly controlled, especially in fetus formation or abnormal results will produce a defective fetus. This can only be the result of design. A designer is required.

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