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	<title>Comments on: Influenza &#8211; more diverse than you thought</title>
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	<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/</link>
	<description>Meddling with things mankind is not meant to understand.  Also, pictures of my kids</description>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-50668</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 20:17:37 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-50668</guid>
		<description>Please, instead of taking some casual on-line approximation as a &quot;third opinion&quot;,  look at the actual peer-reviewed literature that discusses the observations, how they&#039;re observed, weaknesses and strengths of each observation, etc.  I&#039;ve given you some references, Vince has given you some pointers if you read the article I linked to.  There is simply tons of stuff on this, you don&#039;t need to resort to online throwaways.  That claimed error rate is simply wrong, it&#039;s 10-fold off.  &lt;br&gt;&lt;br&gt;If you need more pointers, a useful starting point is Virus Res (2005) 107:141-149, which specifically explains why that error rate is a vast underestimate and gives a long list of determined error rates.  &lt;br&gt;&lt;br&gt;Oh, hell, I have it open anyway, I&#039;ll show it to you (I guess I can&#039;t include images in here, the table is &lt;A HREF=&quot;http://www.iayork.com/Images/2010/3-27-10/VirusErrorRates.png&quot; rel=&quot;nofollow&quot;&gt;here&lt;/A&gt;) &lt;br&gt;&lt;br&gt;Please, do some real reading, and some thinking, before you post on this again.  You are starting with a correct observation (the 40-ish per genome per year, on a population basis).  Instead of using this to reject a fundamental fact of virology, you need to understand how the two observations are consistent, and what that means for natural selection on the virus.   It&#039;s a very interesting and really profound connection, and you can&#039;t possibly understand influenza until you put these two facts together.</description>
		<content:encoded><![CDATA[<p>Please, instead of taking some casual on-line approximation as a &#8220;third opinion&#8221;,  look at the actual peer-reviewed literature that discusses the observations, how they&#39;re observed, weaknesses and strengths of each observation, etc.  I&#39;ve given you some references, Vince has given you some pointers if you read the article I linked to.  There is simply tons of stuff on this, you don&#39;t need to resort to online throwaways.  That claimed error rate is simply wrong, it&#39;s 10-fold off.  </p>
<p>If you need more pointers, a useful starting point is Virus Res (2005) 107:141-149, which specifically explains why that error rate is a vast underestimate and gives a long list of determined error rates.  </p>
<p>Oh, hell, I have it open anyway, I&#39;ll show it to you (I guess I can&#39;t include images in here, the table is <a HREF="http://www.iayork.com/Images/2010/3-27-10/VirusErrorRates.png" rel="nofollow">here</a>) </p>
<p>Please, do some real reading, and some thinking, before you post on this again.  You are starting with a correct observation (the 40-ish per genome per year, on a population basis).  Instead of using this to reject a fundamental fact of virology, you need to understand how the two observations are consistent, and what that means for natural selection on the virus.   It&#39;s a very interesting and really profound connection, and you can&#39;t possibly understand influenza until you put these two facts together.</p>
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		<title>By: gsgs</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-50667</link>
		<dc:creator>gsgs</dc:creator>
		<pubDate>Sat, 27 Mar 2010 19:53:05 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-50667</guid>
		<description>here I found a 3rd opinion:&lt;br&gt;&lt;a href=&quot;http://www.cs.cmu.edu/%7Eroni/ResearchGuide-ViralEvolution.html&quot; rel=&quot;nofollow&quot;&gt;http://www.cs.cmu.edu/~roni/ResearchGuide-Viral...&lt;/a&gt;&lt;br&gt;&lt;br&gt; &gt; All RNA viruses have roughly the same underlying mutation rate (~3 x 10^-5 errors per &lt;br&gt; &gt; replication per base).&lt;br&gt;&lt;br&gt;{are these nucleotides or amino acids ?}&lt;br&gt;&lt;br&gt;3 times more than your 10^-4 but 10 times less than my 40/3/365/13000</description>
		<content:encoded><![CDATA[<p>here I found a 3rd opinion:<br /><a href="http://www.cs.cmu.edu/%7Eroni/ResearchGuide-ViralEvolution.html" rel="nofollow"></a><a href="http://www.cs.cmu.edu/~roni/ResearchGuide-Viral.." rel="nofollow">http://www.cs.cmu.edu/~roni/ResearchGuide-Viral..</a>.</p>
<p> &gt; All RNA viruses have roughly the same underlying mutation rate (~3 x 10^-5 errors per <br /> &gt; replication per base).</p>
<p>{are these nucleotides or amino acids ?}</p>
<p>3 times more than your 10^-4 but 10 times less than my 40/3/365/13000</p>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-50666</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 18:58:15 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-50666</guid>
		<description>&lt;EM&gt;very high = 3*10^-3 per position per year for flu-A, that&#039;s what you usually find.&lt;br&gt;I don&#039;t see why this can be much higher for a single replication cycle without&lt;br&gt;the mutations accumulating over the year&lt;/EM&gt;&lt;br&gt;&lt;br&gt;You&#039;re simply wrong.  This isn&#039;t guesswork, it&#039;s basic virology.  &lt;br&gt;&lt;br&gt;&lt;EM&gt;hmm, 1993. Now we have genbank.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;Oh, come on.  I cited a 1993 article to show this is basic and has been known for decades.  This is absolutely basic, first-year-undergraduate, virology -- RNA-dependent RNA polymerases are highly error prone and make, as a reasonable average, one error per genome per replication, and therefore RNA viruses exist as a quasispecies, a cloud, not a single sequence.&lt;br&gt;&lt;br&gt;&lt;EM&gt;it can&#039;t be. That&#039;s simple logics and not virology and I&#039;d bet on it.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;It can be.  It&#039;s simple math and simple virology. &lt;br&gt;&lt;br&gt;Vincent Racaniello has a good primer on the basic virology you might find useful.  Check out &lt;A HREF=&quot;http://www.virology.ws/2009/05/10/the-error-prone-ways-of-rna-synthesis/&quot; rel=&quot;nofollow&quot;&gt;&quot;The error-prone ways of RNA synthesis&quot;&lt;/A&gt; and the posts before and after it.   As he says there (and again, this isn&#039;t airy hypothetical stuff, it&#039;s basic, fundamental, undergraduate stuff):&lt;br&gt;&lt;br&gt;&lt;BLOCKQUOTE&gt;Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily. For example, it is the driving force behind influenza viral antigenic drift.&lt;/BLOCKQUOTE&gt;</description>
		<content:encoded><![CDATA[<p><em>very high = 3*10^-3 per position per year for flu-A, that&#39;s what you usually find.<br />I don&#39;t see why this can be much higher for a single replication cycle without<br />the mutations accumulating over the year</em></p>
<p>You&#39;re simply wrong.  This isn&#39;t guesswork, it&#39;s basic virology.  </p>
<p><em>hmm, 1993. Now we have genbank.</em></p>
<p>Oh, come on.  I cited a 1993 article to show this is basic and has been known for decades.  This is absolutely basic, first-year-undergraduate, virology &#8212; RNA-dependent RNA polymerases are highly error prone and make, as a reasonable average, one error per genome per replication, and therefore RNA viruses exist as a quasispecies, a cloud, not a single sequence.</p>
<p><em>it can&#39;t be. That&#39;s simple logics and not virology and I&#39;d bet on it.</em></p>
<p>It can be.  It&#39;s simple math and simple virology. </p>
<p>Vincent Racaniello has a good primer on the basic virology you might find useful.  Check out <a HREF="http://www.virology.ws/2009/05/10/the-error-prone-ways-of-rna-synthesis/" rel="nofollow">&#8220;The error-prone ways of RNA synthesis&#8221;</a> and the posts before and after it.   As he says there (and again, this isn&#39;t airy hypothetical stuff, it&#39;s basic, fundamental, undergraduate stuff):</p>
<blockquote><p>Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily. For example, it is the driving force behind influenza viral antigenic drift.</p></blockquote>
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		<title>By: gsgs</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-50665</link>
		<dc:creator>gsgs</dc:creator>
		<pubDate>Sat, 27 Mar 2010 18:25:59 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-50665</guid>
		<description>thanks for replying.&lt;br&gt;&lt;br&gt; &gt;&gt; most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. &lt;br&gt; &gt;&gt; We only see ~40 mutations accumulated per year, one every 10 days. &lt;br&gt; &gt;&gt; Most mutations are synonymous and selection should have little effect.&lt;br&gt; &gt;&lt;br&gt; &gt; No, you&#039;re mixing two very different things up here.  We only see 40 (or whatever) &lt;br&gt; &gt; mutations accumulate per year in the flu population, &lt;br&gt; &gt; after selection at the population level&lt;br&gt;&lt;br&gt;which should be small for the majority of synonymous mutations&lt;br&gt;&lt;br&gt; &gt; and cycling through multiple hosts.&lt;br&gt;&lt;br&gt;the virus won&#039;t know what host it is in&lt;br&gt;&lt;br&gt; &gt; But I&#039;m talking raw mutation frequency, the error rate of the viral RNA polymerase;&lt;br&gt; &gt; and that&#039;s very high.&lt;br&gt;&lt;br&gt;very high = 3*10^-3 per position per year for flu-A, that&#039;s what you usually find.&lt;br&gt;I don&#039;t see why this can be much higher for a single replication cycle without&lt;br&gt;the mutations accumulating over the year&lt;br&gt;&lt;br&gt; &gt; It&#039;s long been known that the error rate is so high, in fact, that essentially every &lt;br&gt; &gt; replication incorporates at least one error.&lt;br&gt;&lt;br&gt;a replication in one cell may generate 10000 copies. How many of these contain at least&lt;br&gt;one mutation ? When you say : at least one, then I agree. But not more than 50%&lt;br&gt;&lt;br&gt; &gt; For example (one of many):&lt;br&gt; &gt; there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, &lt;br&gt; &gt; vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per &lt;br&gt; &gt; genome per replication&lt;br&gt; &gt; --Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. &lt;br&gt; &gt; Sci. USA Vol. 90, pp. 4171-4175, May 1993  &lt;br&gt;&lt;br&gt;hmm, 1993. Now we have genbank.&lt;br&gt;&lt;br&gt; &gt; That means that, far from 90% of viruses in a host being identical, essentially all flu viruses &lt;br&gt; &gt; in a host are different.&lt;br&gt;&lt;br&gt;it can&#039;t be. That&#039;s simple logics and not virology and I&#039;d bet on it.&lt;br&gt;&lt;br&gt; &gt; Thanks for posting those links, but you&#039;ll notice that most of them are either things &lt;br&gt; &gt; I&#039;ve posted (including the post you&#039;re replying to), or papers I cited in those posts.&lt;br&gt;&lt;br&gt;maybe. Just what I found when searching. Maybe I can complete/improve it later if you want.</description>
		<content:encoded><![CDATA[<p>thanks for replying.</p>
<p> &gt;&gt; most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. <br /> &gt;&gt; We only see ~40 mutations accumulated per year, one every 10 days. <br /> &gt;&gt; Most mutations are synonymous and selection should have little effect.<br /> &gt;<br /> &gt; No, you&#39;re mixing two very different things up here.  We only see 40 (or whatever) <br /> &gt; mutations accumulate per year in the flu population, <br /> &gt; after selection at the population level</p>
<p>which should be small for the majority of synonymous mutations</p>
<p> &gt; and cycling through multiple hosts.</p>
<p>the virus won&#39;t know what host it is in</p>
<p> &gt; But I&#39;m talking raw mutation frequency, the error rate of the viral RNA polymerase;<br /> &gt; and that&#39;s very high.</p>
<p>very high = 3*10^-3 per position per year for flu-A, that&#39;s what you usually find.<br />I don&#39;t see why this can be much higher for a single replication cycle without<br />the mutations accumulating over the year</p>
<p> &gt; It&#39;s long been known that the error rate is so high, in fact, that essentially every <br /> &gt; replication incorporates at least one error.</p>
<p>a replication in one cell may generate 10000 copies. How many of these contain at least<br />one mutation ? When you say : at least one, then I agree. But not more than 50%</p>
<p> &gt; For example (one of many):<br /> &gt; there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, <br /> &gt; vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per <br /> &gt; genome per replication<br /> &gt; &#8211;Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. <br /> &gt; Sci. USA Vol. 90, pp. 4171-4175, May 1993  </p>
<p>hmm, 1993. Now we have genbank.</p>
<p> &gt; That means that, far from 90% of viruses in a host being identical, essentially all flu viruses <br /> &gt; in a host are different.</p>
<p>it can&#39;t be. That&#39;s simple logics and not virology and I&#39;d bet on it.</p>
<p> &gt; Thanks for posting those links, but you&#39;ll notice that most of them are either things <br /> &gt; I&#39;ve posted (including the post you&#39;re replying to), or papers I cited in those posts.</p>
<p>maybe. Just what I found when searching. Maybe I can complete/improve it later if you want.</p>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-50664</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 18:06:30 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-50664</guid>
		<description>&lt;EM&gt;most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. We only see ~40 mutations&lt;br&gt;accumulated per year, one every 10 days. Most mutations are synonymous and selection&lt;br&gt;should have little effect.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;No, you&#039;re mixing two very different things up here.  We only see 40 (or whatever) mutations accumulate per year in the flu population, after selection at the population level and cycling through multiple hosts.  But I&#039;m talking raw mutation frequency, the error rate of the viral RNA polymerase; and that&#039;s very high.  It&#039;s long been known that the error rate is so high, in fact, that essentially every replication incorporates at least one error.  For example (one of many):&lt;br&gt;&lt;br&gt;&lt;BLOCKQUOTE&gt;there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per genome per replication&lt;/BLOCKQUOTE&gt;&lt;br&gt;--Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4171-4175, May 1993  &lt;br&gt;&lt;br&gt;That means that, far from 90% of viruses in a host being identical, essentially all flu viruses in a host are &lt;EM&gt;different&lt;/EM&gt;.&lt;br&gt;&lt;br&gt;Thanks for posting those links, but you&#039;ll notice that most of them are either things I&#039;ve posted (including the post you&#039;re replying to), or papers I cited in those posts.</description>
		<content:encoded><![CDATA[<p><em>most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. We only see ~40 mutations<br />accumulated per year, one every 10 days. Most mutations are synonymous and selection<br />should have little effect.</em></p>
<p>No, you&#39;re mixing two very different things up here.  We only see 40 (or whatever) mutations accumulate per year in the flu population, after selection at the population level and cycling through multiple hosts.  But I&#39;m talking raw mutation frequency, the error rate of the viral RNA polymerase; and that&#39;s very high.  It&#39;s long been known that the error rate is so high, in fact, that essentially every replication incorporates at least one error.  For example (one of many):</p>
<blockquote><p>there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per genome per replication</p></blockquote>
<p>&#8211;Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4171-4175, May 1993  </p>
<p>That means that, far from 90% of viruses in a host being identical, essentially all flu viruses in a host are <em>different</em>.</p>
<p>Thanks for posting those links, but you&#39;ll notice that most of them are either things I&#39;ve posted (including the post you&#39;re replying to), or papers I cited in those posts.</p>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-43572</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 16:17:37 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-43572</guid>
		<description>Please, instead of taking some casual on-line approximation as a &quot;third opinion&quot;,  look at the actual peer-reviewed literature that discusses the observations, how they&#039;re observed, weaknesses and strengths of each observation, etc.  I&#039;ve given you some references, Vince has given you some pointers if you read the article I linked to.  There is simply tons of stuff on this, you don&#039;t need to resort to online throwaways.  That claimed error rate is simply wrong, it&#039;s 10-fold off.  &lt;br&gt;&lt;br&gt;If you need more pointers, a useful starting point is Virus Res (2005) 107:141-149, which specifically explains why that error rate is a vast underestimate and gives a long list of determined error rates.  &lt;br&gt;&lt;br&gt;Oh, hell, I have it open anyway, I&#039;ll show it to you:&lt;br&gt;&lt;br&gt;&lt;img title=&quot;RNA virus error rates&quot; src=&quot;http://www.iayork.com/Images/2010/3-27-10/VirusErrorRates.png&quot; alt=&quot;RNA virus error rates&quot; &lt;/a&gt; &lt;br&gt;&lt;br&gt;Please, do some real reading, and some thinking, before you post on this again.  You are starting with a correct observation (the 40-ish per genome per year, on a population basis).  Instead of using this to reject a fundamental fact of virology, you need to understand how the two observations are consistent, and what that means for natural selection on the virus.   It&#039;s a very interesting and really profound connection, and you can&#039;t possibly understand influenza until you put these two facts together.</description>
		<content:encoded><![CDATA[<p>Please, instead of taking some casual on-line approximation as a &#8220;third opinion&#8221;,  look at the actual peer-reviewed literature that discusses the observations, how they&#39;re observed, weaknesses and strengths of each observation, etc.  I&#39;ve given you some references, Vince has given you some pointers if you read the article I linked to.  There is simply tons of stuff on this, you don&#39;t need to resort to online throwaways.  That claimed error rate is simply wrong, it&#39;s 10-fold off.  </p>
<p>If you need more pointers, a useful starting point is Virus Res (2005) 107:141-149, which specifically explains why that error rate is a vast underestimate and gives a long list of determined error rates.  </p>
<p>Oh, hell, I have it open anyway, I&#39;ll show it to you:</p>
<p>&lt;img title=&#8221;RNA virus error rates&#8221; src=&#8221;http://www.iayork.com/Images/2010/3-27-10/VirusErrorRates.png&#8221; alt=&#8221;RNA virus error rates&#8221;  </p>
<p>Please, do some real reading, and some thinking, before you post on this again.  You are starting with a correct observation (the 40-ish per genome per year, on a population basis).  Instead of using this to reject a fundamental fact of virology, you need to understand how the two observations are consistent, and what that means for natural selection on the virus.   It&#39;s a very interesting and really profound connection, and you can&#39;t possibly understand influenza until you put these two facts together.</p>
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		<title>By: gsgs</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-43571</link>
		<dc:creator>gsgs</dc:creator>
		<pubDate>Sat, 27 Mar 2010 15:53:05 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-43571</guid>
		<description>here I found a 3rd opinion:&lt;br&gt;&lt;a href=&quot;http://www.cs.cmu.edu/%7Eroni/ResearchGuide-ViralEvolution.html&quot; rel=&quot;nofollow&quot;&gt;http://www.cs.cmu.edu/~roni/ResearchGuide-Viral...&lt;/a&gt;&lt;br&gt;&lt;br&gt; &gt; All RNA viruses have roughly the same underlying mutation rate (~3 x 10^-5 errors per &lt;br&gt; &gt; replication per base).&lt;br&gt;&lt;br&gt;{are these nucleotides or amino acids ?}&lt;br&gt;&lt;br&gt;3 times more than your 10^-4 but 10 times less than my 40/3/365/13000</description>
		<content:encoded><![CDATA[<p>here I found a 3rd opinion:<br /><a href="http://www.cs.cmu.edu/%7Eroni/ResearchGuide-ViralEvolution.html" rel="nofollow"></a><a href="http://www.cs.cmu.edu/~roni/ResearchGuide-Viral.." rel="nofollow">http://www.cs.cmu.edu/~roni/ResearchGuide-Viral..</a>.</p>
<p> &gt; All RNA viruses have roughly the same underlying mutation rate (~3 x 10^-5 errors per <br /> &gt; replication per base).</p>
<p>{are these nucleotides or amino acids ?}</p>
<p>3 times more than your 10^-4 but 10 times less than my 40/3/365/13000</p>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-43569</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 14:58:15 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-43569</guid>
		<description>&lt;EM&gt;very high = 3*10^-3 per position per year for flu-A, that&#039;s what you usually find.&lt;br&gt;I don&#039;t see why this can be much higher for a single replication cycle without&lt;br&gt;the mutations accumulating over the year&lt;/EM&gt;&lt;br&gt;&lt;br&gt;You&#039;re simply wrong.  This isn&#039;t guesswork, it&#039;s basic virology.  &lt;br&gt;&lt;br&gt;&lt;EM&gt;hmm, 1993. Now we have genbank.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;Oh, come on.  I cited a 1993 article to show this is basic and has been known for decades.  This is absolutely basic, first-year-undergraduate, virology -- RNA-dependent RNA polymerases are highly error prone and make, as a reasonable average, one error per genome per replication, and therefore RNA viruses exist as a quasispecies, a cloud, not a single sequence.&lt;br&gt;&lt;br&gt;&lt;EM&gt;it can&#039;t be. That&#039;s simple logics and not virology and I&#039;d bet on it.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;It can be.  It&#039;s simple math and simple virology. &lt;br&gt;&lt;br&gt;Vincent Racaniello has a good primer on the basic virology you might find useful.  Check out &lt;A HREF=&quot;http://www.virology.ws/2009/05/10/the-error-prone-ways-of-rna-synthesis/&quot; rel=&quot;nofollow&quot;&gt;&quot;The error-prone ways of RNA synthesis&quot;&lt;/A&gt; and the posts before and after it.   As he says there (and again, this isn&#039;t airy hypothetical stuff, it&#039;s basic, fundamental, undergraduate stuff):&lt;br&gt;&lt;br&gt;&lt;BLOCKQUOTE&gt;Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily. For example, it is the driving force behind influenza viral antigenic drift.&lt;/BLOCKQUOTE&gt;</description>
		<content:encoded><![CDATA[<p><em>very high = 3*10^-3 per position per year for flu-A, that&#39;s what you usually find.<br />I don&#39;t see why this can be much higher for a single replication cycle without<br />the mutations accumulating over the year</em></p>
<p>You&#39;re simply wrong.  This isn&#39;t guesswork, it&#39;s basic virology.  </p>
<p><em>hmm, 1993. Now we have genbank.</em></p>
<p>Oh, come on.  I cited a 1993 article to show this is basic and has been known for decades.  This is absolutely basic, first-year-undergraduate, virology &#8212; RNA-dependent RNA polymerases are highly error prone and make, as a reasonable average, one error per genome per replication, and therefore RNA viruses exist as a quasispecies, a cloud, not a single sequence.</p>
<p><em>it can&#39;t be. That&#39;s simple logics and not virology and I&#39;d bet on it.</em></p>
<p>It can be.  It&#39;s simple math and simple virology. </p>
<p>Vincent Racaniello has a good primer on the basic virology you might find useful.  Check out <a HREF="http://www.virology.ws/2009/05/10/the-error-prone-ways-of-rna-synthesis/" rel="nofollow">&#8220;The error-prone ways of RNA synthesis&#8221;</a> and the posts before and after it.   As he says there (and again, this isn&#39;t airy hypothetical stuff, it&#39;s basic, fundamental, undergraduate stuff):</p>
<blockquote><p>Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily. For example, it is the driving force behind influenza viral antigenic drift.</p></blockquote>
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		<title>By: gsgs</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-43568</link>
		<dc:creator>gsgs</dc:creator>
		<pubDate>Sat, 27 Mar 2010 14:25:59 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-43568</guid>
		<description>thanks for replying.&lt;br&gt;&lt;br&gt; &gt;&gt; most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. &lt;br&gt; &gt;&gt; We only see ~40 mutations accumulated per year, one every 10 days. &lt;br&gt; &gt;&gt; Most mutations are synonymous and selection should have little effect.&lt;br&gt; &gt;&lt;br&gt; &gt; No, you&#039;re mixing two very different things up here.  We only see 40 (or whatever) &lt;br&gt; &gt; mutations accumulate per year in the flu population, &lt;br&gt; &gt; after selection at the population level&lt;br&gt;&lt;br&gt;which should be small for the majority of synonymous mutations&lt;br&gt;&lt;br&gt; &gt; and cycling through multiple hosts.&lt;br&gt;&lt;br&gt;the virus won&#039;t know what host it is in&lt;br&gt;&lt;br&gt; &gt; But I&#039;m talking raw mutation frequency, the error rate of the viral RNA polymerase;&lt;br&gt; &gt; and that&#039;s very high.&lt;br&gt;&lt;br&gt;very high = 3*10^-3 per position per year for flu-A, that&#039;s what you usually find.&lt;br&gt;I don&#039;t see why this can be much higher for a single replication cycle without&lt;br&gt;the mutations accumulating over the year&lt;br&gt;&lt;br&gt; &gt; It&#039;s long been known that the error rate is so high, in fact, that essentially every &lt;br&gt; &gt; replication incorporates at least one error.&lt;br&gt;&lt;br&gt;a replication in one cell may generate 10000 copies. How many of these contain at least&lt;br&gt;one mutation ? When you say : at least one, then I agree. But not more than 50%&lt;br&gt;&lt;br&gt; &gt; For example (one of many):&lt;br&gt; &gt; there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, &lt;br&gt; &gt; vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per &lt;br&gt; &gt; genome per replication&lt;br&gt; &gt; --Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. &lt;br&gt; &gt; Sci. USA Vol. 90, pp. 4171-4175, May 1993  &lt;br&gt;&lt;br&gt;hmm, 1993. Now we have genbank.&lt;br&gt;&lt;br&gt; &gt; That means that, far from 90% of viruses in a host being identical, essentially all flu viruses &lt;br&gt; &gt; in a host are different.&lt;br&gt;&lt;br&gt;it can&#039;t be. That&#039;s simple logics and not virology and I&#039;d bet on it.&lt;br&gt;&lt;br&gt; &gt; Thanks for posting those links, but you&#039;ll notice that most of them are either things &lt;br&gt; &gt; I&#039;ve posted (including the post you&#039;re replying to), or papers I cited in those posts.&lt;br&gt;&lt;br&gt;maybe. Just what I found when searching. Maybe I can complete/improve it later if you want.</description>
		<content:encoded><![CDATA[<p>thanks for replying.</p>
<p> &gt;&gt; most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. <br /> &gt;&gt; We only see ~40 mutations accumulated per year, one every 10 days. <br /> &gt;&gt; Most mutations are synonymous and selection should have little effect.<br /> &gt;<br /> &gt; No, you&#39;re mixing two very different things up here.  We only see 40 (or whatever) <br /> &gt; mutations accumulate per year in the flu population, <br /> &gt; after selection at the population level</p>
<p>which should be small for the majority of synonymous mutations</p>
<p> &gt; and cycling through multiple hosts.</p>
<p>the virus won&#39;t know what host it is in</p>
<p> &gt; But I&#39;m talking raw mutation frequency, the error rate of the viral RNA polymerase;<br /> &gt; and that&#39;s very high.</p>
<p>very high = 3*10^-3 per position per year for flu-A, that&#39;s what you usually find.<br />I don&#39;t see why this can be much higher for a single replication cycle without<br />the mutations accumulating over the year</p>
<p> &gt; It&#39;s long been known that the error rate is so high, in fact, that essentially every <br /> &gt; replication incorporates at least one error.</p>
<p>a replication in one cell may generate 10000 copies. How many of these contain at least<br />one mutation ? When you say : at least one, then I agree. But not more than 50%</p>
<p> &gt; For example (one of many):<br /> &gt; there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, <br /> &gt; vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per <br /> &gt; genome per replication<br /> &gt; &#8211;Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. <br /> &gt; Sci. USA Vol. 90, pp. 4171-4175, May 1993  </p>
<p>hmm, 1993. Now we have genbank.</p>
<p> &gt; That means that, far from 90% of viruses in a host being identical, essentially all flu viruses <br /> &gt; in a host are different.</p>
<p>it can&#39;t be. That&#39;s simple logics and not virology and I&#39;d bet on it.</p>
<p> &gt; Thanks for posting those links, but you&#39;ll notice that most of them are either things <br /> &gt; I&#39;ve posted (including the post you&#39;re replying to), or papers I cited in those posts.</p>
<p>maybe. Just what I found when searching. Maybe I can complete/improve it later if you want.</p>
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		<title>By: iayork</title>
		<link>http://www.iayork.com/MysteryRays/2009/08/28/influenza-more-diverse-than-you-thought/comment-page-1/#comment-43567</link>
		<dc:creator>iayork</dc:creator>
		<pubDate>Sat, 27 Mar 2010 14:06:30 +0000</pubDate>
		<guid isPermaLink="false">http://www.iayork.com/MysteryRays/?p=1367#comment-43567</guid>
		<description>&lt;EM&gt;most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. We only see ~40 mutations&lt;br&gt;accumulated per year, one every 10 days. Most mutations are synonymous and selection&lt;br&gt;should have little effect.&lt;/EM&gt;&lt;br&gt;&lt;br&gt;No, you&#039;re mixing two very different things up here.  We only see 40 (or whatever) mutations accumulate per year in the flu population, after selection at the population level and cycling through multiple hosts.  But I&#039;m talking raw mutation frequency, the error rate of the viral RNA polymerase; and that&#039;s very high.  It&#039;s long been known that the error rate is so high, in fact, that essentially every replication incorporates at least one error.  For example (one of many):&lt;br&gt;&lt;br&gt;&lt;BLOCKQUOTE&gt;there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per genome per replication&lt;/BLOCKQUOTE&gt;&lt;br&gt;--Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4171-4175, May 1993  &lt;br&gt;&lt;br&gt;That means that, far from 90% of viruses in a host being identical, essentially all flu viruses in a host are &lt;EM&gt;different&lt;/EM&gt;.&lt;br&gt;&lt;br&gt;Thanks for posting those links, but you&#039;ll notice that most of them are either things I&#039;ve posted (including the post you&#039;re replying to), or papers I cited in those posts.</description>
		<content:encoded><![CDATA[<p><em>most flu-viruses (&gt;90% in a host I guess) are still identical, genetically. We only see ~40 mutations<br />accumulated per year, one every 10 days. Most mutations are synonymous and selection<br />should have little effect.</em></p>
<p>No, you&#39;re mixing two very different things up here.  We only see 40 (or whatever) mutations accumulate per year in the flu population, after selection at the population level and cycling through multiple hosts.  But I&#39;m talking raw mutation frequency, the error rate of the viral RNA polymerase; and that&#39;s very high.  It&#39;s long been known that the error rate is so high, in fact, that essentially every replication incorporates at least one error.  For example (one of many):</p>
<blockquote><p>there is a clear central tendency for lytic RNA viruses (bacteriophage Qfi, poliomyelitis, vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of 1 per genome per replication</p></blockquote>
<p>&#8211;Rates of spontaneous mutation among RNA viruses. John W. Drake.   Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4171-4175, May 1993  </p>
<p>That means that, far from 90% of viruses in a host being identical, essentially all flu viruses in a host are <em>different</em>.</p>
<p>Thanks for posting those links, but you&#39;ll notice that most of them are either things I&#39;ve posted (including the post you&#39;re replying to), or papers I cited in those posts.</p>
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