In class, the professor said that there is about 8% of protein-coding genes in human. I wonder how biologists estimate this without annotating all of human genes. Thank you!
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1$\begingroup$ What do you mean by "without annotating"? Without a minimal annotation of the transcriptional and translational features this is obviously not possible. After they got the sequence they had to read it. What is your question exactly? $\endgroup$– DavidJun 27, 2018 at 19:37
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S/he's off by about 6 - 7%.
As per the national human genome research institute approximately 1% of the human genome encodes proteins. We can tell this by looking at the sequence (which we're now able to do quite quickly) and identifying those portions of the sequence can be translated to protein using the genetic code.
Scientists have been able to identify approximately 21,000 protein-coding genes, in large part by using the long-ago established genetic code. But these protein-coding regions make up only approximately 1 percent of the human genome...
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$\begingroup$ You are taking some wrong assumptions. There are plenty of regions that contain open reading frames in the human genome and a high fraction of them are translated into "proteins". This was recently seen in ribosome profiling experiments. That does not mean that these translated ORF are proteins in the sense that they perform a function. Most of them are noise as they are transcribed and translated in small quantities. Additional evidence to consider a translated region as a true protein is usually conservation. However very recent proteins will not appear even in closely related species. $\endgroup$– biojlJun 28, 2018 at 13:10
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$\begingroup$ @biojl This is a statement by the NHGRI, the institute at the NIH that oversees genomics research. It represents consensus in the field. There is, of course, more to that goes into it, but you find out how much of the genome codes proteins "in large part by using the long-ago established genetic code". We use conservation of these ORFs as well, but recent work suggests we should be a little more liberal with what we consider a functional protein. $\endgroup$– De NovoJun 28, 2018 at 16:10
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$\begingroup$ The consensus in the field of genomics (where I belong) has changed quite a lot since 2012... Those statements were true back then but the beauty of science is that it changes when new data or new ways of looking at it appear. $\endgroup$– biojlJul 2, 2018 at 9:10
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$\begingroup$ @biojl personally, my time in the lab is remote, but I like to think I'm still on top of things, and current research is relevant to me. Do we really not think that 1-2% of genome encodes proteins anymore? Do we not start that estimation by looking for ORFs? $\endgroup$– De NovoJul 2, 2018 at 17:41
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It is important to remember that protein-coding genes have a start and an end, exons and introns, and identifiable promotors. Knowing that these factors exist and how to identify them (usually by their unique DNA sequences, the frequency they occur and their sequence lengths) we can identify these sequences as part of whole genome analyses.
Next-generation sequencing made it possible to sequence the entire genome of a human in a matter of days, if not hours. This massive database makes it possible to identify it's variable elements. Now, knowing where a promotor is, the following start codon of a gene can be found along with its stop codon. This leads to identifying open reading frames (ORFs).
Now it is simple, in that simply counting all the ORFs in relation to the other structural and "nonsense" DNA and the percentage of protein coding sequences can be determined. Remember that this is the norm, however there is still much we do not know about the human genome. There may be more protein-coding genes with unknown promotors that we do not know of. So always keep on asking!