…and this is a 
Lander began by saying he wasn't an evolutionist — an interestingly narrow definition of the term. He's a fan of the research, but considers himself a biomedical geneticist, as if that was something different.
Having entire genomes of many species available for quantitative analysis is going to lead to a qualitative change in the science we can do.
He gave a pocket summary of the human genome project. Mouse genome followed, then rat and dog, and now have sequence (to varying degrees of completeness) of 44 species, out of 4600 mammals. Within Homo, there's the hapmap project and the 1000 genomes project, so at least in us we're going for depth and breadth of coverage.
Sequencing technology is rapidly accelerating. Exponential growth in the number of nucleotides sequenced per year. Exponentially on a log scale! We're developing a tremendous amount of data acquisition capability. We'll be able to address mechanisms of physiology and evolution, and learning about the particulars of history.
Lander focuses on genome-wide studies. Evolutionary conservation is a guide to extracting information from the genome. Showed synteny diagrams of mouse and human, and discussed analyses that allow you to identify highly conserved pieces, bits that might have significant function.
Number of genes is low, 20,500. Early higher numbers he admitted were inflated a bit by prior expectations; when they had a good estimate of 30,000, they decided to waffle and call it 30-40,000.
If genes are counted by homology, how do we know there aren't many more genes that don't have homology. If that were case, the number of genes in humans would still be close to the estimated numbers in chimp and macacque.
There are also well-conserved non-coding regions in DNA. 5% of the genome is under selection: coding 1.2%, non-coding 3.8%. Found 200 gene poor regions that contain key developmental genes, and many of the conserved non-coding regions are associated with them.
Long intergenic non-coding DNA: pretty much all of the genome is transcribed, but the vast majority of this is simply noise. There about a dozen regions known where transcription of non-coding DNA seem to be conserved evolutionarily, and have some function: they be transcriptional repressors.
Mechanism of evolutionary innovation in coding genes: examples of whole genome duplication, divergence and loss, all of which can be demonstrated by comparison with an outgroup. Outgroup comparisons can demonstrate whole genome duplications.
Mechanisms of innovation in non-coding regions: about 84% of conserved DNA is shared between marsupials and placentals, suggesting that about 16% of changes are novel. About 15% of placental specific CNEs are derived from transposons.
With 29 mammalian genomes compared, they have 4 substitutions per site, a detection limit of about 10 bp, and 2.8 million features detected. We have a lot of detail that can be extracted from the data sets.
We can find evidence of positive selection. Using chicken as an outgroup, we can identify genes that have undergone major changes in humans but not chimps. Comparision across 29 mammals shows even more. What we're finding is that these evolutionarily significant genes are enriched for developmental genes.
Analysis within the human species shows that we are a young population that expanded rapidly from a small initial population of 10,000 individuals. Can now screen for associations between single-nucleotide polymorphisms and disease. We can now screen for 2 million polymorphisms in a single pass on a chip. Have now identified 500 loci associated with common traits. Most have very modest effects and only contribute to a small part of the heritability of the trait. Where is all the missing heritability? Missing loci, missing alleles, and non-additive effects of loci.
Positive selection in human history: can use hapmap data to find 300 regions with outlier distributions that suggest they have been the target of selection. Combining statistical tests narrows the specificity of identification to a size roughly equal to a single gene making it possible to identify specific genes with an interesting selective history (work in press by Pardis Sabeti). There are themes: many of these genes are involved in resisting infectious disease.
Genomics is experiencing an explosion of data that represents a huge opportunity for future discovery.
Life Science
Comments
Posted by: molliebatmit | October 30, 2009 5:04 PM
I think it's fair to narrowly define yourself scientifically.
For example, I'm a neurobiologist, and my work touches on and uses the tools of development, evolution, and genetics. I wouldn't call myself a geneticist, though, as I feel that implies I know a lot more than I do about genetics.
Posted by: Anonymous | October 30, 2009 6:29 PM
Are some of the words getting dropped in these posts? My grammar radar is blazing away.
Posted by: Anonymous | October 30, 2009 6:32 PM
Nevermind, just realized these are notes from a lecture of some sort
Posted by: Meathead | October 30, 2009 6:47 PM
Long intergenic non-coding DNA: pretty much all of the genome is transcribed, but the vast majority of this is simply noise. There about a dozen regions known where transcription of non-coding DNA seem to be conserved evolutionarily, and have some function: they be transcriptional repressors.
Huh? the whole genome is transcribed, not just open reading frames? Are we talking about micro-RNAs or siRNAs here?
Posted by: Kamaka
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October 30, 2009 6:48 PM
Could not possibly, huh? Argument by assertion.
While there is a component of randomness to mutation, there is also an inevitability to mutation; incorrect copying, radiation and the like.
Think deep time, man.
PS Intelligent design is total bullshit. No hypothesis, certainly no theory. Just made-up shit.
Posted by: Nerd of Redhead, OM
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October 30, 2009 6:53 PM
Wrong on all accounts, starting the with imaginary designer. And you wonder why you are scorned?Posted by: 'Tis Himself, OM
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October 30, 2009 7:49 PM
Winston Wolfe, meet killfile.
Posted by: Nerd of Redhead, OM
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October 30, 2009 7:52 PM
Yep WW is our old "friend" CW, dungeon resider. For obvious, except to him, reasons...Posted by: 'Tis Himself, OM
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October 30, 2009 8:21 PM
Nerd,
I didn't realize that until a little while ago when I say his patented argument from personal incredulity displayed on other threads.
Posted by: Kamaka
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October 30, 2009 8:25 PM
NoR, 'Tis
I had no idea. Writes well for a clueless type.
Posted by: David Marjanović, OM | October 30, 2009 8:45 PM
A very conservative count. Try 5200 or 5500...
See that quotation mark in front of "My god, it looks designed!"?
By far not only. In a stunning case of Stupid Design, transcription initiation and especially termination signals are so rare that lots of junk gets transcribed into RNA that is then destroyed again. An incredible waste (lengthening an RNA strand by one nucleotide costs not one but two molecules of ATP!) that probably contributes measurably to our body temperature but has no other benefits.
What a pathetic misinterpretation of alternative splicing.
What a waste of line breaks. Dude, this here isn't a typewriter, it's a computer. Line wrapping is done automatically. You do not need to press Enter at the end of a line and risk ending up with line breaks in stupid places that make reading more difficult.
"Almost infinite". What was the number creationists cannot write again?
Posted by: kopd | October 30, 2009 8:45 PM
@Kamaka
He's copying and pasting. He said so.
Posted by: David Marjanović, OM | October 30, 2009 8:48 PM
I quoted this but overlooked it:
How stupid. Someone here doesn't know what a genome is and not even that the human genome isn't the only one to have been sequenced.
Posted by: Kamaka
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October 30, 2009 9:04 PM
See that quotation mark in front of "My god, it looks designed!"?
Didn't think much of it 'till after the fact.
He's copying and pasting.
Yah, now I'm embarrassed at having been sucked in to his simulation of erudition. Serves me right for breaking my "don't feed the trolls" rule.
Posted by: Neanderthal allele | October 30, 2009 9:11 PM
Genome sequences provide us with fundamentally important insights into the evolutionary pattern and process, and the field is about to take another significant step forward, which will be real revolution.
The current 2nd generation DNA sequencing technology can generate about 18 GigaBases of sequence in one run (the human genome is about 3.5 GB). The technology can determine millions of short sequences in parallel and because it is such a large number from throughout the genome, the result is numerous short overlapping sequences. When assembled together these can make up a complete genome sequence. The standard these days is to sequence a genome about 100x (using billions of short overlapping sequences) before it is considered a clean and finished sequence. The technology was not a bad step forward, but it still takes a few months or weeks to get the sequence information. Followed by several months of computer-based data assemble.
The 3rd generation sequencing technology is due to be released this month and is called single-molecule sequencing. This technology can sequence a complete genome within 15 minutes (one of the leading platforms is www.pacificbiosciences.com). A consortium of scientists have been meeting over the past six months and are planning to use this new technology to sequence the complete genomes of 10,000 vertebrate species (see genome10k.soe.ucsc.edu/). The comparative genomics that will surface in the next decade is going to be not much short of the complete genetic resolution of vertebrate evolution. This will be an incredible insight into the evolutionary process.
Hold on to your hats and wave goodbye to some big knowledge gaps.
Posted by: gillt
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October 30, 2009 10:04 PM
PZ: "Exponentially on a log scale!"
That's the only way to make sense of such numbers. As for our lab, we've contributed a fraction of a fraction: kras, exon 1,2 (12 tumor samples, Danio rerio).
Posted by: kopd | October 30, 2009 10:04 PM
@kamaka
You're not alone. I didn't realize it was a dungeon denizen until after composing a response. Wasted my time.
Posted by: Nerd of Redhead, OM
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October 30, 2009 10:13 PM
Nah, he just thinks he is smarter than everybody else, except he ignores evidence, and isn't constrained by ethics. The Rev. BDC smelled him out (may his beer be forever hoppy, and his whiskey single malt). I almost forgive the good Rev. for the typo cooties when he does it...Posted by: leepicton
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October 30, 2009 11:16 PM
I sort of understood all the neat new techniques being described; it was tremendously exciting. And, I was even able to determine all by myself that the entry by "Winston Wolfe" was incomprehensible gobbledegook - I am learning stuff! Please hurry, scientists, I am getting too old too fast, and so want so see a time when so many knowledge gaps are filled that fundies (all anti-science types, actually)will have no other recourse than to stick their fingers in their ears and say "lalalalala" I can't hear you!"
Oh. Someone just said they are already doing that. Carry on.
Posted by: Meathead | October 31, 2009 2:55 AM
leepicton said:I am getting too old too fast, and so want so see a time when so many knowledge gaps are filled that fundies (all anti-science types, actually)will have no other recourse than to stick their fingers in their ears and say "lalalalala" I can't hear you!"
Fundies will always find gaps even if they have to make them themselves with a handaxe.
David M wrote:By far not only. In a stunning case of Stupid Design, transcription initiation and especially termination signals are so rare that lots of junk gets transcribed into RNA that is then destroyed again. An incredible waste (lengthening an RNA strand by one nucleotide costs not one but two molecules of ATP!) that probably contributes measurably to our body temperature but has no other benefits.
Heh, so to paraphrase Winston Wolfie: My god it looks like crap!
Posted by: beth | October 31, 2009 12:29 PM
re: neanderthal allele
If they can pull off that single-molecule sequencing, it will be wonderful to see! I left molbio to be a mom when I got burnt out on genotyping bizillions of polymorphisms by hand. I've always said that I would get back into science when they can sequence a whole genome in one day. Maybe I should be dusting off my resume.
Posted by: Meathead | October 31, 2009 4:20 PM
Neaderthal, will this new method solve the problem of sequencing the many tandem repeats. I seem to recall that repetitious sequences are particularly hard to get at since when you cut them up they all look the same.
Posted by: brittany burks | January 3, 2010 1:15 PM
nc pst ws lkng fr nfrmtn prtnng t ths tpc kp th grt rtcls cmng :)