Monday, August 26, 2013

Coming to a town near you!

I'll be doing a little bit of traveling this Fall, and I'd love to see you!

Tuesday September 10, 2013
The Pennsylvania State University, State College, Pennsylvania
Time/Place TBD
I will be in town the 9th and 10th!

Friday September 13, 2013
Syracuse-Dunbar-Avoca High School, Syracuse, Nebraska
I am VERY excited to be talking with the students where I went to high school!!

Monday September 16, 2013
The University of Kansas (KU), Lawrence, Kansas
12:00-12:50, 3012 Haworth
I'll be on campus ~10-4pm

October 22-26, 2013
American Society of Human Genetics 2013 meeting
At ASHG 2013 I will be tweeting (@mwilsonsayres), presenting a poster on the identification of evolutionary strata, and co-moderating with Maja Bucan the session:

Wednesday, October 23, 2:00pm-4:15pm

Friday, August 23, 2013

Y and mtDNA are not Adam and Eve: Part 3 - Resolving a discrepancy

Co-posted at Panda's Thumb, where you can join in the comments.

Part 1: Y and mtDNA are not Adam and Eve.
Part 2: What it means to be the Most Recent Common Ancestor (MRCA)

On to part 3. Except, what's this? Someone has beat me to it? Gasp!

Okay, go read Dienekes' Anthropology blog post about the two recent Y papers. I agree with all of the critiques and summaries of both the Poznik et al. (2013) and the Francalacci et al. (2013) papers. Perhaps the best part of this summary:
"And, indeed, the fact that the two are of different ages is not particularly troubling or in need of remedy, since for most reasonable models of human origins we do not expect them to be of the same age."
But, let's see if I can provide a little more background (you did go read Dienekes' post, right?). Good. But, just in case you didn't, a brief summary of some of the findings of Poznik et al. (2013):

Poznik et al. sequenced a lot of Y chromosomes
Poznik et al sequenced the Y chromosomes of 69 people. Yes, this is more than enough individuals to address this question of the time to the MRCA. Very few lineages, even two can allow us to estimate the time to the most recent common ancestor. Each lineage will contain information (mutations) that have accumulated since they diverged. But, comparing closely related lineages will lead to a lower TMRCA, while comparing very divergent lineages will lead to an older TMRCA. You can learn a lot about the process of how the Y chromosomes diverged by having the intermediate lineages, but they aren't necessary for computing the TMRCA.

In the pictures below, the red dots are observed mutations.

If there aren't very many mutations between two regions, then their TMRCA will not be very long ago:

Comparing two closely related lineages gives a younger TMRCA

If more Y chromosomes are analyzed from very different regions, then more mutations will be observed between any pair of lineages, and the TMRCA will be older.
The more diverged the lineages, the older the TMRCA

But, for just estimating the TMRCA, the total number of lineages will have very little (if any) effect on the age estimated, whereas the number of differences observed on the most diverged Y chromosome will be very important.
For estimating TMRCA,  the most diverged lineage (Y5) will have the biggest effect. 

How to estimate the time to the most recent common ancestor (TMRCA)
The time estimated depends very little on the number of lineages (see above). Rather, it is extremeley dependent on:
1) how different the lineages are from one another (how many mutations are observed); and,
2) how quickly those differences are estimate to have accumulated (the rate of mutation).

The Y TMRCA is older than most previous estimates
The time to the most recent common ancestor of the Y chromosome, as computed by Poznik et al. is older than most other estimates. But why?
- The diversity of the Y chromosomes included (the more diverse the Y chromosomes, the older the time to their most recent common ancestor)
- the high sequencing coverage, which means that more mutations can be identified
- The rate of mutation the authors use is 0.82x10-9 mutations per base pair per year (95% CI: 0.72-0.92x10-9 mutations per base per year). This mutation rate is lower than estimates from a Y-linked pedigree (1x10-9 mut/bp/year), and from human-chimpanzee divergence, which lengthens the tree compared to previous estimates. The mutation rate was calibrated assuming that humans reached the Americas ~15,000 years ago. Such an exact timing for the entry of modern humans to the Americas is not yet certain.

The Y TMRCA is not as old as it could be
Mendez et al. (2013) recently described a Y chromosome that is much older (67% w/ 95% CI:35-126%) than all other known Y chromosomes. This Y chromosome has not yet been sequenced to the coverage of the Y chromosomes in the Poznik et al. (2013) paper, and was not included in their analysis. If it were included, all other factors remaining the same, the TMRCA for the Y chromosome would be much older than the TMRCA for the mtDNA in the same paper.

The mtDNA estimate is younger than many other estimates
Although there has been a lot of discussion of the Y chromosome being older than previous estimates, I haven't seen a lot of discussion about the mtDNA, which at 99-148,000 years in this analysis, is estimated a bit younger than previous work (~200,000 years ago). Part of this younger estimate can be contributed to the calibrated mutation rate used. The authors compute a calibrated mtDNA mutation rate of 2.3x10-8 mutations per base pair per year (95% CI: 2-2.5x10-8 mut/bp/year), which is higher than some previous estimates (e.g., 1.7x10-8) - meaning the total tree will be somewhat shorter than previous estimates, all else being equal.

I am excited to see if there exist pockets of mtDNA diversity, such as the highly divergent Y lineage that was recently identified.

So, what is the right mutation rate?
If the mutation rate used across studies varies so much, then it is no surprise that the TMRCA estimates are not consistent across studies. Which one is correct? Well, of course it is... _. Okay, so the real answer is that it is not so simple. I know, I know, not the answer you were looking for. It's like when you have a multiple choice question with four answers and you have to choose the one that is most correct. I never did well on those. I'll dodge this bullet by pointing you to a wonderful discussion about human mutation rates by John Hawks.

It is exciting, though, that with the recent ability to isolate and sequence DNA from ancient samples, we should start getting more precise and accurate, estimates of the human mutation rate on the different chromosomes.

One more thing - there is no reason to expect the TMRCA for the Y and mtDNA to be the same.
The process of working backwards to estimate the time to the most recent common ancestor is a paring down of lineages until only one linage remains. This is called coalescent theory. Because they lack recombination, both the Y and the mtDNA represent a single linage, a single coalescent process going back in time. Any number of events could have happened that resulted in a set of mtDNA or Y chromosome lineages being retained longer or shorter than expected. The TMRCA is only the time to the *most* recent common ancestor. There were other ancestors, but we can only identify the most recent. And there are a myriad of reasons why these might not necessarily date to the same time for the Y and mtDNA.

But, why don't we expect the TMRCA to be the same?
To be clear, it is not that we expect them to be different. More that we don't expect them to be the same.

I'm going to make a gross over-simplification (we can do more math in the comments, if you like). But, bear with me. Let's say that you had two dice. If you roll each die once, just once, would you be very surprised if the numbers didn't match up? No, not at all. Likewise, you wouldn't be shocked if, say, each die showed a six. And, if one die showed a two, while the other showed a six, you probably wouldn't call it a discrepancy. Why? Because you only rolled them once.

Similarly (although with a bit more math), when tracing back the Y common ancestor and the mtDNA common ancestor, we should not be surprised if their TMRCAs are different, nor if they overlap.

They represent only one roll of the dice.

 2013 Aug 2;341(6145):562-5. doi: 10.1126/science.1237619.

Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females.


Tuesday, August 20, 2013

Back-up Child Care for almost all.

I just received this wonderful email in my inbox: UC Berkeley is piloting a program to offer up to 60 hours of  low-cost back up childcare to Berkeley undergraduate and graduate students. It is modeled after a program that is available to Berkeley faculty. Yay!!

Oh, wait. I am a postdoc...

... just a minute...

Okay - because I'm an eternal optimist, I just went and checked to see if maybe I would still qualify, but nope. I am not eligible.

I am not sure whether to be angry, or disappointed, or happy, or defeated.

Well, yay for undergrad and grad students. Let's see if they can extend it to postdocs in the near future.
I am pleased to announce that last week UC Berkeley became the first public university in the U.S. to offer both graduate and undergraduate students highly subsidized access to back-up child care.  This program enables student parents to focus on study sessions, writing papers, or travel to attend conferences or give presentations when their usual caregiving arrangements are unavailable.

The pilot program — modeled on one which our faculty have found useful since 2009 — is linked to a student’s current registration status (not conditioned on campus employment). Students with dependent children will be eligible for up to 60 hours per academic year of in-home and/or center-based care by professional caregivers, with a very low hourly co-pay.  As the pilot program’s capacity is limited, students will be registered on a first-come/first-served basis.  

This extension of the campus’s family-friendly services was initiated by the Graduate Division, endorsed by the Chancellor’s Advisory Committee on Student Services and Fees (CACSSF), and approved by Chancellors Robert Birgeneau and Nicholas Dirks. The program is administered by the Graduate Division in partnership with the Student Parent Center in the Division of Equity & Inclusion.  It is generously sponsored by the Hutto Patterson Charitable Foundation.

Details are at  Please join me in getting the word out to all student parents at Berkeley, as well as prospective students who will appreciate our campus’s pathbreaking family-friendly culture.

George W. Breslauer
Executive Vice Chancellor and Provost

Thursday, August 15, 2013

Thank you to the Bay Area Skeptics!!

Last night I had the amazing privilege to give a SkepTalk to the Bay Area Skeptics. What an amazing group of people.

The talk was about 40 minutes about "Sex, Male Bias, and Degeneration," which expanded is: Sex Chromosome Evolution, Male Biased Mutation, and Degeneration on the Y chromosome.

Everything, from the invitation, to the set-up, to the audience participation, to the questions afterwards was excellent! And everyone was so excited and engaged. There were tons and tons of questions. I think there was at least half an hour of discussion afterwards.

Near the end, one of the audience members shouted out, "So, you really do have the best job in the world!". Yes! I love science. I love communicating it. I get to do what I love every day (do I have to count revising papers?). Don't get me wrong, science isn't the easiest job in the world, but for me, it is the very best.

And, next month they're having Brian Switek come to talk about "My Beloved Brontosaurus"!! I will have to go, if for no other reason than to let Little Bear meet her favorite author.

Tuesday, August 13, 2013

MBE preprint policy

A follow-up:

In May, I wrote a letter to the SMBE council, requesting that they please consider allowing review of manuscripts that have also been submitted to preprint servers, such as the arXiv.

This came about because discussions on twitter suggested that the journal of Molecular Biology and Evolution (MBE) would refuse to review any paper that had previously been submitted to a preprint server. I was surprised to hear it, sent an inquiry to the Society. Turns out, it was true.

So, I wrote a letter detailing why I, as a Society member, would like to see our Society accept manuscripts for review that have also been submitted to preprint servers, at both MBE and GBE (Genome Biology and Evolution).

To my amazement, I was invited to comment on the suggested policy for MBE!

At the annual Society meeting in July it was announced that MBE will allow articles that have been submitted to a preprint server to be reviewed! As I understand it, the stipulation will be that articles submitted to a preprint server will be required to choose (and pay for) the "Open Access" option. I would do this anyway, as I suspect many preprint submitters would (or I hope that they would).

The main MBE website now links to the very detailed Oxford Press, "Author Self-Archiving Policy."

At the conference, I had some enlightening discussions with people who are not advocates of open access, and do not see the value in the arXiv. I was also surprised to learn that some thought my letter was a political move (?), and, perhaps less surprised to learn that there were concerns that I would publish private email responses for the public to see. Personally, I will always assume a conversation is private unless there is a mutual decision to make it public (or if it is abusive, and needs to be reported). But, do I understand and respect concerns about privacy. However, with it comes to scientific research and methods, my opinion is:

The more accessible and transparent the better.

Thursday, August 8, 2013

Y and mtDNA are not Adam and Eve: Part 2 - What it means to be the Most Recent Common Ancestor

Co-posted at Panda's Thumb - please add comments there.

Part 1 is here.

There were more than two.
One of the misleading aspects of the "Adam and Eve" analogy, is the implication that there were only two humans alive at that time. In the video below I explain what the mtDNA is, how it can be used to trace back to find a common mtDNA ancestor, and why this genetic female was not alone. The same logic applies to the Y chromosome ancestor. Scientists estimate there were approximately 5,000 genetic females and 5,000 genetic males in the ancestral population of anatomically modern humans.

Talking with people and making this video brought up a couple other important points that are difficult to summarize in a sentence, so I'll expand upon later:

1. One person (or two people) did not have the ancestral state of all of our DNA.
The person whose cells housed the common mtDNA ancestor (or Y ancestor) also had all of the other chromosomes (1-22 and X), but did not house the common ancestor of each of these chromosomes. These non-sex chromosomes are a lot more complicated. This touches on why it is also misleading to refer to the common ancestor of genetic "males" versus "females." Genetic females are not only their mtDNA - we also have 22 non-sex chromosomes, and two X chromosomes! Genetic males are not only their Y (and mtDNA), they also have 22 non-sex chromosomes and one X chromosome! Because the non-sex chromosomes (autosomes) can swap DNA, and are inherited through both the sperm and the egg, they much more complicated history than the Y and mtDNA.

2. A lower bound, not a point estimate.
Tracing back to the common ancestral mtDNA or the common ancestral Y chromosome does not tell us when anatomically modern humans arose. We can estimate the TMRCA, or the Time to the Most Recent Common Ancestor, but this mtDNA surely existed much further back in time.

Consider this:

If you didn't watch the movie, I'll remind you that in this example, you and your sister are my genetic cousins, and our moms are sisters. In the above example you can see how we can trace all modern mtDNA back to a common mtDNA ancestor (the dotted lines indicate more than one connection is not shown).

Now imagine that a horrible disaster killed off everyone except for our family:

Then, the Most Recent Common Ancestor of all mtDNA really is just our grandma. The previous mtDNA ancestor still existed, but she is no longer the MOST recent.

There is so much to talk about here! My list keeps getting longer.

Coming soon:

  • What I do understand about the paper, and how it fits with recent Y discoveries.
  • What I don't (yet) understand about the results.
  • You'll say I'm being to harsh, but I do want to discuss why the title is also misleading to people (separate sexes existed waaaay before humans, and waaaay before genetic sex determination).
  • And, for fun (and a friend) - How fast would evolution have to be if all of modern humans really did descend from only two people - with LOTS of assumptions

Wednesday, August 7, 2013

Upcoming Public Skeptalk!

I just got forwarded an announcement for my upcoming public lecture/discussion!!
What: Sex, Male Bias, and Degeneration
When: Wednesday, August 14, 2013  07:30 PM - 09:30 PM
Where: La Peña Cultural Center Lounge 3105 Shattuck Avenue Berkeley, CA
Cost: FREE
Why: Because we're curious creatures

I am so excited to have been invited to give an upcoming Skeptalk! You are all welcome come and join in the discussion. The more the merrier!

Below is the announcement that was sent out (modified/shortened from a version I sent a month ago). But, given the recent interest in the TMRCAs of the Y and mtDNA, I'm considering editing the lecture to include some discussion of this new content as well.

Sex, Male Bias, and Degeneration
by Dr. Melissa A. Wilson Sayres

The human X and Y chromosomes evolved from a non-sex ancestor. The X is still regular-sized, but the Y is degraded and puny. Dr. Wilson Sayers will talk about how this process occurs, and how we can use the sex chromosomes to understand why more nucleotide mutations originate from the sperm than from eggs.

Dr. Melissa A. Wilson Sayres researches human population genetics at UC Berkeley's Miller Institute. She started as a mathematician in Nebraska, learned to program, and then studied sex chromosome evolution at Penn State. She is passionate about studying and communicating evolution research at all levels.

Tuesday, August 6, 2013

Y and mtDNA are not Adam and Eve: Part 1

 Co-posted at Panda's Thumb. If you'd like to comment, please join the discussion here.

This is going to be the first of a several part (at least two, maybe more, however many it takes) series of posts discussing both the science and the science communicating regarding a recent paper:
Science. 2013 Aug 2;341(6145):562-5. doi: 10.1126/science.1237619.

Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females.

First, you should go read it. It is short and sweet, and, yay science!

What I'm going to talk about first is how this paper relates to communicating science. Future posts will expand and elaborate on the research. I'll also note that I am not picking on this paper alone, because several other scientific papers have done the exact same thing. This one is just the most recent incident, and, more personally,  I was actively involved in trying (and failing) to prevent the miscommunication. As such, I feel the need to provide more explanation.

The recent paper did an excellent job of publicizing itself. It has a sexy title, and it mentions, "Adam and Eve" in the main manuscript:
"Dogma has held that the common ancestor of human patrilineal lineages, popularly referred to as the Y chromosome "Adam," lived considerably more recently than the common ancestor of female lineages, the so-called mitochondrial "Eve."
Regardless of the results (which are definitely new, and we'll discuss later), these things alone would get it a lot of press. They are tangible ideas that the public can relate to, and make it easy for a science journalist to build a story around.

But, they are also extremely misleading. I think they are also harmful, in the long-term for educating and communicating with the public.

I was interviewed by two different science writers to comment on this paper, and in both interviews I stressed how inappropriate the "Adam Y" and mitochondrial or "mtDNA Eve" analogies are. You can see how well they took that into consideration: here and here. I really enjoyed talking with the journalists, so hope they won't think I'm picking on them either because, to be fair, nearly every popSci article used this analogy (see here, here, here, and here). I'll take a sentence here to especially note the article by Francie Diep, here, that took a different approach.

While I have several reasons to disliking this analogy, I cannot fault the journalists completely for using it in this instance. Aside from my protests, there is no reason science journalists should think that it is a bad analogy, because it was used in the manuscript (without context or explanation).

Okay, so I'm upset that the paper would reference the "Y Adam" and "mtDNA Eve" without explaining them, but why are these analogies wrong? The public connects to them - they are visual and engaging, so what's the problem?

First, a little background:

Who are Adam and Eve?
If you are not familiar with it, in the Old Testament, one of the creation myths is that God created a man (Adam) and a woman (Eve), and all other humans are descended from this pair of first humans.

Simple enough.

What are the Y and mtDNA?
Each person has half of their DNA from their genetic father (who provided the sperm) and half of their DNA from their genetic mother (who provided the egg).

The Y chromosome passes through the genetic male lineages (genetic males are XY, inherit their Y chromosome from their genetic father, and will pass it on to their genetic sons).

The mtDNA is a small circular piece of DNA that all of us have in our cells, but is only transmitted through the genetic female lineage (the egg contains the mtDNA, so although genetic sons and daughters both receive this mtDNA, only the genetic female lineage makes eggs, so mtDNA is only passed on by daughters).

The Y and mtDNA are unique
Unlike the autosomes, which come in pairs (one copy from genetic mom, one from genetic dad), and can swap DNA, resulting in the mixing up of information from genetic mom and dad, neither the the Y chromosome nor the mtDNA have a partner (Y only from genetic dad, mtDNA only from genetic mom). So, it is somewhat simpler to trace these two pieces of DNA back in time.

Using some math and observations of the numbers of observed changes (mutations) on the Y chromosome and the mtDNA, scientists can estimate how closely related any two Y chromosome, or any two mtDNA are, and when they last shared a common ancestor.

What's the problem with "Y Adam" and "mtDNA Eve"?
If we can estimate the most recent common ancestor of the mtDNA and the most recent common ancestor  of the Y chromosome, isn't this kind of like the creation story of Adam and Eve?


There are several reasons people don't like these analogies, but in my opinion there are two overwhelmingly wrong ideas that get propagated when using them. Applied to genetics, using the creation story of "Adam and Eve" to describe the most recent common ancestor of the Y and mtDNA, respectively, implies that:

Bad analogy #1: There were only two humans alive at that time.

There were several other genetic females living at the time of the person who carried the mtDNA ancestor of us all, and several other genetic males living at the same time as the genetic male who carried the Y chromosome ancestor of modern genetic males.

Bad analogy #2: Y "Adam" knew (presumably intimately) mtDNA "Eve".

Just because the person who carried the ancestral Y chromosome is predicted to live about the same time as the person who carried the ancestral mtDNA (120,000-156,000 years ago for the Y lineage versus 99,000-148,000 years ago for the mtDNA lineage), in no way suggests that they lived at exactly the same time. Although it is short on an evolutionary time scale, those are pretty big time ranges when you're thinking about a human lifespan! Further, even if they happened to live at the exact same time, there is no evidence that they were located in the same region or would have interacted at all.

These two erroneous assumptions stem directly from using the "Adam and Eve" analogy. The public is smart, and while they may not have the vocabulary (heck, people outside of our specific sub-disciplines do not share the same vocabulary), they can understand analogies. When we, as scientists, supply an analogy that doesn't accurately describe the research, it is not the public's fault for misunderstanding the work; it is our fault for misrepresenting it.

There is no reason why the "Y Adam" and "mtDNA Eve" should have been mentioned in the primary manuscript, but if it was necessary, it should have clearly been explained why this analogy is not appropriate.

Well, that's a start.

In the follow-up posts I will go into:
1. More detail describing bad analogy #1 and #2 above, and misunderstandings relating to the title
2. An accessible research summary of the actual paper (yay! - This really is the most fun part.)
3. Addressing questions you all have about this topic!

So, stay tuned!!

Part 2:
Part 3:

Thursday, August 1, 2013

My life as a whole person: Sometimes it isn't about picking your battles

Regardless of how you spend your days, some are just so much busier than others! Today has been one of those days.

This morning I woke up to wonderful news: A paper describing a new algorithm and analysis of the human X chromosome was accepted with minor revisions at Genome Biology and Evolution! I'm co-first author, and although I'm not listed first, for a variety of reasons, I'll be staying up tonight to work on updating the manuscript and figures tonight. In the next couple of weeks I'll write up an accessible research blog post about it to share with you all!

I got into work and met with my undergraduates. One student and I sat down for an hour debugging code. It was really fantastic, actually, to sit and do some of the detective work together. There were a few small errors in the code, but the root problem turned out to be a faulty assumption about the format of the input files. I was so happy to figure it out, but it was especially gratifying to work through it with my student. I couldn't have come up with a better lesson about coding if I had tried!

Then, I sat back down and read an email from Science writer Tia Ghose, asking me to comment on a Y chromosome paper that's being published tomorrow. She's the one who interviewed me last Fall on my work studying diversity across all compartments of the human genome. Of course I was thrilled to talk to her again!

Afterwards I ate lunch with my husband, also a postdoc at Berkeley. I spent the rest of the afternoon working on revisions from the paper from this morning, responding to emails, including working with a collaborator on a grant resubmission, and trying to prioritize my to-do list, which seems to have grown exponentially since last week.

Then, I got an email that the this manuscript was rejected, with the possibility of resubmitting... again. I have two months to complete the suggested revisions, but should probably take a day or two to thoroughly read the comments. It is nice, then, that I have a few other immediate distractions.

One daily distraction is something I let consume my mind, and that is Little Bear. This morning we noshed on Cheerios together, and read books before Scott took her to daycare. This afternoon I jogged to daycare (yay for one mile!), then played with the Little Bear at the Willard Park playground. We met up for a family dinner out at Kiraku (a Japanese tapas restaurant, which none of us are yearning to go back to), then all walked home together. At home we enjoyed Little Bear's antics, she got a bath, then we read books, and tried to get her to bed. Then she got up to pee on the potty. Then back to bed. Then up again to pee on the potty. Then back to bed. Then up once more to pee on the potty (really, how much urine can one toddler have?!). Then, back to bed, and asleep within a few minutes.

Here is the wisdom from Little Bear (2.5yrs old) tonight:

Sometimes it isn't about picking your battles. Sometimes it's just time to laugh. 
I was singing to her tonight - always songs of her request. Tonight she asked for "Baa Baa Black Sheep". If you don't know the song, the first line is:

"Baa baa black sheep, have you any wool?"

Well, Little Bear interrupted me to tell me, "It isn't 'wool' mommy, it's 'woof'." She proceeded to sing the first line "correctly" for me:

"Baa baa black sheep, have you any woof?"

Then she laughed hysterically. I think it was her first attempt at making a  new joke. As infectious as her laughter is, it was pretty funny.

I sang the original version. She corrected me again, then laughed like an evil genius. She knew it was wrong, and I knew it was wrong, so there was no use arguing about it. It wasn't about being right or wrong, it was about taking the time to laugh about something silly, and enjoy the moment.

Today was a series of wonderful moments, and one frustrating moment, but even that has already passed. I'm not saying I wasn't upset about the rejection (I really was), but I felt it, let it consume the time it deserved, and now I'm ready for the next moment. Woof.