Genome complexity: many proteins from a few genes (Introduction)

by David Turell , Thursday, February 11, 2016, 20:58 (3208 days ago) @ David Turell

We have 20,000genes and 100,000 proteins in our bodies. How is that?:-http://medicalxpress.com/news/2016-02-alternative-proteins-encoded-gene-widely.html-" For one, it may help explain how the mere 20,000 protein-coding genes in the human genome - fewer than are found in the genome of a grape—can give rise to creatures of such enormous complexity. Scientists know that the number of different proteins in human cells, thought to be upwards of 100,000, far exceeds the number of genes, but many questions have remained. Do most of those proteins have a unique function in the cell, or do their roles sometimes overlap? The discovery that different protein isoforms encoded by the same gene may have divergent functions on a larger scale than realized suggests that they vastly multiply what our genes are capable of.-***-"One of the ways that cells produce multiple protein isoforms from individual genes is a process called alternative splicing. Most human genes contain multiple segments called exons, separated by intervening non-coding sequences called introns. In the cell, different combinations of these individual exons are "glued" or spliced together to generate a final expressed gene product; thus, a single gene can encode a set of distinct, but related protein isoforms, depending on the specific exons that are spliced. One isoform, for example, may result from splicing exons A-B-C-D of a particular gene. Another may arise from the skipping of exon C, resulting in a product with only exons A-B-D.-***-"Of the roughly 20,000 genes in the human genome that code for proteins, researchers concentrated on about eight percent. Using ORF-Seq, they ultimately created a collection of 1,423 protein isoforms for 506 genes, of which more than 50 percent were entirely novel gene products. They subjected 1,035 of these protein isoforms through a mass screening test that paired them with 15,000 human proteins to see which would interact.-"'The exciting discovery was that isoforms coming from the same gene often interacted with different protein partners," remarked Gloria Sheynkman, PhD, of Dana-Farber and one of the lead authors. "This suggests that the isoforms play very different roles within the cell" - much as siblings with different careers often interact with different sets of friends and co-workers.-"The researchers found that in most cases, related isoforms shared less than half of their protein partners. Sixteen percent of related isoforms share absolutely no protein partners. "From the perspective of all the protein interactions within a cell, related isoforms behave more like distinct proteins than minor variants of one another.-***-"Intriguingly, isoforms that stem from a minuscule difference in DNA - a difference of just one letter of the genetic code—sometimes had starkly different roles within the cell, researchers found. At the same time, related isoforms that are structurally quite different may have very similar roles.-"Quite often, the interaction partners of related isoforms vary from tissue to tissue, the researchers found. In the liver, for example, an isoform may interact with one set of proteins. In the brain, a relative of that isoform may interact with a largely different set of protein partners."-Comment: And all of this process is in the non-coding part of DNA, the so-called 'junk' part. Too complex for chance.