Nielsen Group

I know – that’s a first.  The supreme court made a wise and unanimous decision on the Association for Molecular Pathology v. Myriad Genetics case.  You can no longer patent a gene. However, the supreme court upheld Myriad Genetics’ rights to patent cDNA from BRCA1 and BRCA2 – which might explain why Myriad Genetics’ stock jumped after the ruling.  Apparently, the investors had feared worse.  Exactly what a patent on cDNA entails may be up to future litigation, but it should not preclude many common genotyping platforms as a diagnostic tool for BRCA1 and BRCA2 mutations.

What are the long term consequences of the ruling?  We can probably expect private companies to invest less in basic research on the molecular genetics of disease.  It might be harder to make a profit on discovering disease related mutations.  On the other hand, it will be easier to develop new diagnostic tools based one existing knowledge.  We might expect a shift in focus in private companies from basic research towards development of diagnostics. That is not necessarily a bad thing.  But somebody else has to pick up the slack on basic research.

The mantra for funding of genomics research at the National Institute of Health (NIH) – the major funding body of genomic and medical research – has been ‘translational’.  Apparently, the phase in genomic research in which we focus on basic discoveries is over.  Now we need to focus on translating these discoveries into medical applications – diagnostics and treatments.  That is all good – but with the expected fallout of the supreme court ruling,  somebody has to continue the drive for basic research.  It is time for NIH to once again step up on funding for basic research in the genomic sciences.

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Addendum:  Hilariously, while Scalia voted in favor of the ruling – he dissented on the basic principles of molecular biology. Apparently, it is not only global warming and evolution that is being challenged.  I expect soon to see a dissent on the shape of the earth or the placement of the earth in the solar system.

Hello Everyone,

We are excited to be hosting the 8th meeting of the Bay Area Population Genomics group at UCSF Mission Bay on June 8th!  Thanks to support from Ancestry.com and the Institute for Quantitative Biosciences (QB3 @ UCSF), this conference will include breakfast and lunch.  In addition, we will also have a reception during the poster session, so we highly encourage you to preview your work at BAPG before heading out to summer conferences.

Please register at http://tinyurl.com/a8h6uo8, and sign up to give a talk or poster.  Registration is again free, but required by June 3rd.

There is paid parking in the lot/garage at the corner of 4th and 16th streets, and we have a limited number of parking passes for people that sign up to present and/or make a strong effort to carpool (please email me for details).

We are very much looking forward to seeing you at UCSF in a few weeks!

Best,

Ryan

This is an excellent opportunity to share ideas, learn about new topics, and meet other researchers! Unfortunately, this is the same weekend as the Miller Symposium that I’ve been co-organizing, but I encourage you all to participate.

I was recently interviewed by Alan Boyle at NBC to comment on:

An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree

Fernando L. Mendez, Thomas Krahn, Bonnie Schrack, Astrid-Maria Krahn, Krishna R. Veeramah, August E. Woerner, Forka Leypey Mathew Fomine, Neil Bradman, Mark G. Thomas, Tatiana M. Karafet and Michael F. Hammer

I do think the paper is very exciting. The identification of a new Y lineage is always interesting, and this one appears to be very long-lived. However, after a more careful reading, and some thought, I am not sure I agree with the way the TMRCA (Time to the Most Recent Common Ancestor) of the Y chromosomes was computed. And the ancient TMRCA depends quite a bit on the TMRCA. I have written up my thoughts and submitted them to the American Journal of Human Genetics, AJHG. The AJHG has a pretty strict pre-print policy (emphasis is mine):

“Work intended for submission to AJHG, currently under consideration at AJHG, or in press at AJHG may not be discussed with the media before publication. Providing preprints, granting interviews, discussing data with members of the media, or participating in press conferences in advance of publication without prior approval from the AJHG editorial office may be grounds for rejection.“

But, I have gotten permission from the editor to discuss my thoughts about the submitted manuscript with colleagues (and in blog form). I am sharing the full AJHG manuscript with Mendez, but want to summarize here:

Mendez et al. identify a Y chromosome haplotype that has not been characterized before and, with more work, they determine that it is nearly identical to a small group of Y chromosomes from Cameroon. They also estimate the TMRCA for the Y haplotype phylogeny, including this new Y chromosome and find it to be at least twice as large as anyone else, and as noted by the authors themselves, this TMRCA is inconsistent with what is known in the human fossil record.  While the new Y haplotype does increase the diversity, and thus the TMRCA, the TMRCA calculation is extremely sensitive to the mutation rate used. Mendez et al. advocate for using a mutation rate from human pedigree data instead of from comparative genomics. They then derive a mutation for the human Y chromosome from the mutation rate estimated from autosomal pedigree data. The equation they use assumes a linear correlation between the mutation rate on the autosomes, and the mutation rate on the Y chromosome.

I present a case in my response that: 1) it is not appropriate to assume a linear correlation between the mutation rate on the autosomes and the mutation rate on the Y chromosome; 2) the mutation rate Mendez et al. computed for the Y from autosomal data is an order of magnitude lower than the mutation rate that was measured for the Y chromosome from a pedigree analysis in 2009; 3) the resulting TMRCA is inconsistent with what is known about diversity on the mtDNA, autosomes and X chromosome. Further, our own research suggests that selection is acting to reduce diversity on the Y chromosome relative to the autosomes, X, and mtDNA, which would make an extremely high TMRCA on the Y even more incompatible with observed data.

As such, I am curious why the mutation rate measured from Y chromosomes in a pedigree analysis was not used. I think the results would still be quite exciting and novel. Given what we expect to be strong purifying selection acting to reduce diversity on the Y, the same arguments, of ancient population structure  or even archaic introgression may still apply to this unique Y haplotype.

Cross-posted at my blog.

This is a repost from here.

Last week I went with a group of postdocs and grad students to teach a lesson on Phylogenetics to local high school freshman. I had the foresight to do a pre-assessment and post-assessment (those results will be coming soon), but I wanted to start by sharing how this experience made me think about how we introduce the concept of evolution.

During one of the breaks, I spoke with the students’ teacher. I told him how, to me, one of the neatest things about studying evolution is understanding the tremendous effects of genetic drift. It amazes me that so much of the natural variation we observe within and across species is due simply to stochastic processes in the population. Selection doesn’t need to enter the picture. It does, of course, most popularly through positive selection acting to increase the frequency of beneficial alleles, and also (and perhaps more often) through purifying selection acting to remove deleterious alleles, or through balancing selection to maintain a balance of alleles that might be harmful under some conditions and helpful under others. And, all of this natural selection can affect the frequency of linked neutral alleles.

But, a large proportion of natural variation doesn’t result from natural selection. It can just accumulate and drift to high frequency or fixation through neutral processes. This could be as populations separate geographically from each other, or if one population experiences a severe reduction in size, or any number of scenarios that change the history of the population. How cool is that?!

Later the teacher went through their evolution lesson. I am, first of all, very excited that they have a whole unit on evolution. They spend several classes introducing the concept of natural selection, giving examples of different island populations of lizards adapting to their new environments, and learn to build phylogenetic trees using the physical features of the lizards, and then analyze DNA sequences from the lizards. Cool!

But, the whole lesson focused on the small part of evolution that is positive natural selection. Sure, positive selection is the cool kid on the block, but I think it would be very instructive, and perhaps even more convincing to also introduce purifying selection (because, hey, there are a lot of sequence/functions/features conserved across any chosen clade), and the awesomeness that is neutral evolution (because otherwise we’re training students to look for zebras see function everywhere they look).

I guess I shouldn’t be surprised by this when, at the NESCent Catalysis meeting today, very qualified evolutionary biologists suggested that one of the primary topics journalists should know about science is natural selection, and then gave a detailed example of positive selection acting on a population.

Maybe natural selection is a good place to start to introduce evolution. It is tangible, easy to understand, and, there are very accessible examples of positive selection. But, there is so much more to evolution that positive selection. I hope educators can see the importance of reaching beyond positive selection.

I’m live tweeting (@mwilsonsayreS) today through Sunday from NESCent:

Reporting Across the Culture Wars: http://www.nescent.org/cal/calendar_detail.php?id=935

hashtag: #evocomm

A paper was recently published in Genome Biology and Evolution that attacks questions the claims made by the 2012 main ENCODE Consortium paper.

Given that Berkeley has the good fortune of housing people with opposing (and even some with moderate) opinions about the ENCODE project, the Center for Theoretical and Evolutionary Genetics will soon be hosting a friendly discussion about the recent paper from Graur et al.

You are cordially invited to participate in this amiable discussion:

ENCODE discussion
Monday March 11, 2013
10:30am
2063 VLSB

The Spring 2013 CTEG meeting schedule is here: http://trump.popgen.dk/peterb/cteg.html

Reformatting manuscripts for a new journal is, in my opinion, one of the most tedious parts of being a scientist. I won’t say that it is a total waste of time, but it comes close.

I do understand that each journal has a unique format, structure and feel. Each journal wants to make its format consistent for its readers. And, each journal has a slightly (or vastly) different audience that its format caters to.

But, sweet, mother of pearl, it can be frustrating for authors to update, change, add, and repackage information for a new journal. This one allows sub-headings, another does not. This one allows you to merge “Results” with “Discussion”, another does not. Some journals and articles have specific word limits, others let you include as much content as you like (although some charge by the page). There are varying limits on the number of tables and figures. Even different pricing for color within figures.

I am very lucky to live in the digital age, where technology exists to easily cut, paste, add, and subtract content. My dad tells me a story where, for his Master’s Thesis, he literally cut out, then taped in new content, because otherwise he would have had to retype the entire tome.

And citations, whew! I am so glad for the software to assist with updating these. There are so many different formats for citing in the text (only the first author’s last name, or up to three authors’ last names, or numbered by the first time the citation is present, or some other variant). The bibliographies can be equally involved regarding the small, but important, differences between journals.

Given all of the changes, and the amount of time, that go into choosing to submit to a journal with a different format (which means that, unfortunately, the manuscript has already been rejected from one journal), there are some good things. A new format does require the author to consider their analysis and results from a new structural perspective, considering how to tell the story in a new way. Hopefully the process will also give authors the chance to catch any minor writing errors, and think of new, clearer ways to explain observations.

I am not entirely convinced that the benefits outweigh the time spent trying to wrangle a manuscript into the appropriate format.

Several people in the lab are applying for jobs right now, so the recent article by Roberta Kwok about elevator talks in Nature seems particularly relevant:

http://www.nature.com/naturejobs/science/articles/10.1038/nj7435-137a?WT.mc_id=TWT_NatureJobs

Nancy Baron is quoted in the article, where she “suggests thinking about four key topics”:
1. the problem
2. why it matters
3. potential solutions
4. the benefits of fixing it.

I wanted to highlight how important I think these short interactions are, not just for explaining science to a lay audience, but for interacting with peers and collaborators. So much of the doctoral work is focused on precision, on figuring out the nitty gritty details, that when we finish, we sometimes forget how long it took to learn and become comfortable with all of the terminology and background. Another aspect of graduate school, and perhaps to a greater extent the postdoc, and applying for jobs, is to emphasize the areas we are experts in. As such, it is difficult to sometimes admit that we don’t know it all. Coupled together, these can result in two very intelligent people speaking to one another, but not fully understanding each other.

While it may seem like an oversimplification (instead of just a simplification), and go against our very nature to provide details, the ability to concisely give an accessible overview of our science can only improve our interactions. Anyone who wants to know more can easily ask.

UC Davis has received funding to host an SMBE Satellite Meeting on Eukaryotic -Omics this spring – meeting dates have been set as Monday April 29 – Thursday May 2nd, 2013, and further details can be found at the meeting website: http://www.smbe.org/eukaryotes

The SMBE Satellite Meeting on Eukaryotic -Omics will bring together an interdisciplinary pool of researchers to discuss current efforts, challenges, and future directions for high-throughput sequencing approaches focused on microbial eukaryotes (environmental studies of non-model organisms). The meeting program will encompass investigations of eukaryote biodiversity, ecology, and evolution, using approaches such as rRNA marker genes, shotgun metagenomics, metatranscriptomics, and computational biology tools and software pipelines.

Program announcements, registration details, and travel award information have been posted to the meeting website. The official conference hashtag will be #SMBEeuks on Twitter.

Our call for travel award applications includes a heavy focus on diversity-encouraging early-career applicants as well as those from underrepresented groups. Please pass on this meeting announcement to anyone who might be interested in attending. Deadline for abstract submission and travel grant applications is Feburary 22, 2013.