Monday, March 16, 2015

No simple genetics for thedress - but does color vision affect compensation for lighting?


In my previous post, I asked whether the way that one sees the now famous dress might have a genetic influence and invited people to send me family data. I got data from 28 families (thank you very much!), and have some conclusions.

First, this cannot be strictly genetic. 
There are examples of monozygotic twins that see the dress differently, and there is a significant minority of people who see it differently from one time to another. These observations are inconsistent with a purely genetic basis. In my own data, I have four families where both parents see blue and black; four of the 12 children in these families see white and gold. I also have nine families where both parents see white and gold; here seven of 20 children see white and gold. Thus, neither trait breeds true. 

However, there are some hints. 
I noticed that 64% of sibling pairs, and 8 of 9 sister pairs, see the dress the same way.  I also noticed that in families where the parents differ, 10/11 daughters see the dress as their father does, which is suggestive of an X-linked partially dominant factor. This led me to ask whether daughters preferentially show the paternal phenotype in families where the parents have the same phenotype. Of cases where I knew the gender of the child, daughters saw the dress as their father did 4/6 times (evenly divided between the two phentoypes). So, overall 14/17 daughters agree with their father. This is significantly different from expected (a simple two-tailed chi-square test with one degree of freedom yields a p value of 0.008).

Since the X chromosome carries the highly polymorphic cone opsin genes that are known to affect color vision, I’m wondering if how one perceives the lighting on the dress (dark vs. light) is affected by these genes. Mechanisms by which women always use color to correct for lighting as their fathers do because of X-linked opsin genes are nearly ruled out by the observation that mutations affecting these genes (red/green color blindness) are recessive. If women used only their father's cone opsin genes, then they would inherit color blindness from their fathers. However, I say "nearly ruled out" because I can think of (admittedly unlikely) scenarios whereby a specific subset of cone cells that plays a role in compensation for lighting also preferentially inactivates the maternal X.  Of course, the limited data here are also consistent with partial dominance, with some other X-linked gene, or, indeed, with no genetic influence at all.
Does normal variation in color vision affect compensation for lighting?
Since the dress illusion is understood to involve compensation for lighting, I am drawn to the question of whether or not variation in color vision affects this compensation. To address this, I’ve come up with a second form, which involves two things:

1) reporting how you see the same image without color
and 

2) taking a vision test (the PANTONE® Online Color Challenge).

I'm asking people to say
-- How they see the dress without color
-- How they see the dress with color and
-- How they score on the online color test (both the numerical score, and, if possible, a screenshot of the results showing the pattern of color discrimination across the spectrum).

The form is available at ongen.us/DressColorForm

This second survey is about the limit of what I can or should do informally through social media. I’m pleased to hear that 23andMe is asking people about how the see the dress. If you have an account with them, then you can contribute at 23andme.com/you/quick_questions/

Note (March 23): 23andMe has posted results from 25,000 responses. They find no strong genetic associations, but an effect of age and an association with whether one lived as a child in a rural (blue and black) or urban (white and gold) setting. They did not look at transmission within families.
blog.23andme.com/23andme-research/genetics-and-that-striped-dress/

Data Summary  March 16
I collected data from 28 families.
The total frequency was approximately half and half. 44 saw blue and black while 54 saw white and gold (six were some sort of intermediate or other; three went back and forth).
In 4 families both parents saw dark colors (blue and black): 6/10 of their children saw colors; 4/10 saw light colors
In 10 families both parents saw light colors: 13/21 children saw dark colors; 7/19 children saw light colors and one child saw the dress differently over time.
In 3 families the mother saw dark colors while the father saw light colors. In this case, 6/6 children saw light colors. All were daughters.
In 6 families the mother saw light while the father saw dark. In this case, 8/11 children (four daughters and four sons) saw dark colors and 3/11 (two sons and one daughter) saw light colors. 3 of 4 daughters saw as their father did.


Mom Dad Families Dark Light Other
Dark Dark 4 8 4 0
Light Light 9 13 7 0
Dark Light 3 0 6 0
Light Dark 6 8 3 0



Sunday, March 01, 2015

Could the dress illusion be genetic?

I am very curious about whether the dress illusion might have a genetic basis. I'm referring to differences in the way that people see the dress in this photo:


Most explanations of the fact that people see this differently (e.g. Steven Pinker, writing in Forbes) have to do with unconscious compensation for lighting. I'm sure that those explanations are generally correct, but which way you see it (whether and how much you compensate) may still have a genetic basis. The fact that very few people report a change in how they see it is consistent with a genetic (or at least biological) basis.

So, I'm trying to find out if how one sees "the dress" is inherited in a Mendelian manner. This is an informal poll (not a proper scientific study) to get a rough idea of inheritance. (Is the trait inherited in a Mendelian way? Is either way of seeing the dress dominant?).

Please respond if (and only if) you belong to a family and have data for both parents and one or more full biological children.

Thanks!  I'll post results here.

To respond, please visit ongen.us/DressGenes and fill out the form.

Sunday, August 10, 2014

Nicolas Wade’s troubling ideas

Among the popular myths about human genetics left over from the era of eugenics, social Darwinism and racism, two are especially relevant to Nicolas Wade’s recent book, “A Troublesome Inheritance: Genes, Race and Human History.”  The first is that natural selection has stopped due to advances in health and medicine, and that, as a result, the unfit are now contributing more to each succeeding generation. Early in his Book, Wade disagrees, stating that “human evolution has been recent, copious and regional”, and much of the first part of the book is devoted to this claim. I think this statement is well-supported by modern genetics. Wade goes further, arguing that in fact, selection favors those who are economically successful. Here, demography and historical records have more to say than genetics, and Wade relies heavily on the work of Gregory Clark, an economic historian at the University of California, Davis, especially the book “A Farewell to Alms” which he reviewed favorably for the New York Times in 2007. I am skeptical about the connection between affluence and Darwinian fitness; I don’t think there are genetic data either way.


Wade gets into trouble when he tries to find support in modern human genetics for a second major myth, which is that humanity can be meaningfully divided into a small number of types (races), and that these types have biologically meaningful differences in things such as intelligence and moral character. Virtually all practicing human population geneticists, including those whose work he cites, are in agreement that this speculation is unsupported, and today’s New York Times carries a succinct statement signed by many of them, featuring a simple message:


We are in full agreement that there is no support from the field of population genetics for Wade’s conjectures.


The letter is here.  The list of signatories, here, contains 139 names, including every prominent human geneticist that I thought to look for.


Why the outcry? People who devote their scientific lives to the study of human genetic variation think about race and popular misconceptions all of the time. They care that their work is accurately represented.


For those who wish to read a more detailed rebuttal of Wade’s arguments, I recommend Jeremy Yoder in the Los Angeles Review of Books, but there are many other good ones. 
The original New York Times book review, by David Dobbs, is here.


For those who want to read less, I leave you with one very brief quote.

He’s claiming to be a spokesperson for the science and, no, he’s not.
- Sarah Tishkoff (David and Lyn Silfen University Professor in the Departments of Genetics and Biology at the Universisty of Pennsylvania, quoted in a Nature News Blog)

----------------------------------------
Postscript (additional commentary):
- Nicolas Wade's reply (New York Times, Aug. 22)
- Marcus W. Feldman in the Computational, Evolutionary and Human Genomics at Stanford blog.
"Echoes of the Past: Hereditarianism and A Troublesome Inheritance" Marcus W. Feldman is the Burnet C. and Mildred Finley Wohlford Professor in the School of Humanities and Sciences at Stanford and a Founding Director of CEHG.

Friday, January 03, 2014

What is a gene?

A gene is all of the DNA elements required in cis for the properly regulated production of a set of RNAs whose sequences overlap in the genome.   
I formulated that definition c. 1990, when I started teaching genetics to graduate students. I think that the course I actually taught was quite different from the plans leading to that formulation, but I remember sitting for several hours in a coffee shop in Newark airport and coming up that definition. This was after the discovery of splicing, transposable elements, remote enhancers, overlapping genes, nested genes, long noncoding RNAs and many short noncoding RNAs, and I imagined discussing literature on each of these topics and its implications for how a gene might be defined. 1990 was before “tweet-length” could be applied, before the discovery of microRNAs and (most significantly) before complete genome sequences and high-throughput data in the style of ENCODE.


I believe this definition has stood the test of time, and that it will continue to provide a useful understanding of what is meant by a gene. 

The fact that it was written to accommodate work that predates complete genome sequences, ChIPseq and whatever methods are developed in the coming years, should be kept in mind as we face hype about new discoveries changing our view of the gene. I predict that later this year some new work will be described as overturning the idea of junk DNA, or the idea of genes as beads on a string, or the notion that genes are merely their coding information, or perhaps all of these. These discoveries will be said to account for the dark matter of the genome and other deep mysteries that were unsolved until now. Faced with that hype, I will link to this post.

In 2014, as part of my plan to write more but shorter posts, I will also report the history of my own understanding of several of the issues that make defining “a gene” problematic.
--------------------
Mark Gerstein almost immediately pointed out that he had published a very similar definition in 2007:

The gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products.
See PubMed: Pubmed ID 17567988 or 
Gerstein lab: http://archive.gersteinlab.org/papers/e-print/grgenerev/preprint.pdf or 
Genome Biology http://genome.cshlp.org/content/17/6/669.long

Thursday, January 02, 2014

Michael Pollan on plant behavior, good and bad

A friend asked my view, so I read the recent article by Michael Pollan in the New Yorker, "The Intelligent Plant."

Michael Pollan is a very good writer and he picked an interesting topic. Plant behavior is indeed fascinating and he does a good job of fascinating his readers without obviously going far beyond what can be supported. I also think he does justice to the community of plant biologists by presenting people's views in their own words. However, I fear that he may have incited enthusiasm for bad science. A critical point in the article occurs when he points out that the argument is about language.
Many of the scientists in [Gagliano's] audience were just getting used to the ideas of plant “behavior” and “memory” (terms that even Fred Sack said he was willing to accept); using words like “learning” and “intelligence” in plants struck them, in Sack’s words, as “inappropriate” and “just weird.” When I described the experiment to Lincoln Taiz, he suggested the words “habituation” or “desensitization” would be more appropriate than “learning.” Gagliano said that her mimosa paper had been rejected by ten journals: “None of the reviewers had problems with the data.” Instead, they balked at the language she used to describe the data. But she didn’t want to change it. “Unless we use the same language to describe the same behavior”—exhibited by plants and animals—“we can’t compare it,” she said.
I agree that unless we should use the same language to describe the same behavior, and applying the words 'behavior' and 'learning' to plants make sense to me. That we use these terms (appropriately, I think) for robots and computers points out that they are neutral with respect to mechanism. However, I don't think that 'intelligence' or 'consciousness' would be appropriate for anything described in this article. The prefix 'neuro' refers to neurons or the nervous system and we know for a fact that plants have nothing like neurons. It's pretty clear that multicellularity evolved independently in plants and animals, and there are important differences, so I find it highly unlikely that plant and animal behavior shares underlying mechanisms. Thus I very much doubt that there is “some unifying mechanism across living systems that can process information and learn.” While fundamental processes common to all life are no doubt shared, more sophisticated signaling is unlikely to be the same. Cell walls make it hard to see how information could be possibly be transmitted through synapses, which are specialized points of contact between neurons. On the other hand, plasmodesmata, channels that allow direct but reguated transport between cells, provide plant cells with the potential for mechanisms unavailable to animal cells. Thus, while communication between the parts of a plant is likely to be as sophisticated, if not more sophisticated, than comparable mechanisms in animals, it is very different, and much less well understood. We would do better to appreciate plants on their own terms. I hope that this article leads more young people into the exciting field of plant signaling. I fear that it may do so for the wrong reasons.


Time-Lapse HD Plants following light

Links:

The Intelligent Plant,” by Michael Pollan in the New Yorker. Dec. 23, 2013. Cleve Backster, an obituary in the New York Times Magazine. The best-selling book, “The Secret Life of Plants,” was inspired by Backster’s research.

Saturday, September 08, 2012

ENCODE: Data, Junk and Hype

This week saw the publication of dozens of papers in Nature, Science and Genome Research that report an initial analysis of data from the Encyclopedia of DNA Elements (ENCODE) project on RNA, transcription initiation, transcription factor association, chromatin structure and histone modification.  The scale of this data is staggering, and it will change how human molecular genetics is done.  Imagine how the field of climatology would be changed if they suddenly had hundreds of years of complete weather data from thousands of weather stations.  This is comparable.
ENCODE data, visualized with the UCSC genome browser.
What ENCODE does not do is fundamentally change our view of what the genome looks like.

The third and fourth sentences of the main article in Nature are these:
These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation.
This "result" has been emphasized in the popular press.


Hype: This lead article in Thursday's copy of the Washington Post Express (a publication of the Washington Post distributed on DC's Metro) is typical of how the story was covered. 
In particular, the conclusion that this study "overturns theory of 'junk DNA' in the genome," which was the title of the article in The Guardian and which was echoed by many who should know better (e.g. Science) is, well, junk. What the ENCODE project has done is locate the sites on human DNA that are represented in RNA, and the sites at which numerous factors bind.  Because 80% of the genome has some biochemical "function" of this sort does not mean that 80% of the genome has some effect on gene expression (although these data will help us immensely in the task of figuring out which noncoding nucleotides do indeed affect gene expression), and we can still be quite sure that most of that 80% does not have any biological function in the usual sense of the word, which is that if you delete it or alter it, something that matters biologically or medically will change.  We still know that most of the millions of single nucleotide polymorphisms that distinguish any two copies of the genome don't matter very much.  It is simply not the case that the vast majority of the human genome has some (biological) functional importance.

Conversely, we have known for a long time that a lot of noncoding DNA does have a function.  Most of the sequence that does matter is not coding.  One measure of that is conservation, and the earliest complete mammalian genomes, in 2005, showed that about 5.3% is conserved among mammals (vs. only about 1% that is coding).  A direct attempt to use ENCODE (and 1000 genomes) data to estimate the fraction of the genome under purifying selection (Ward and Kellis, this week) finds "an additional 4% of the human genome subject to lineage-specific constraints."  While this is a big increase in the estimated fraction of the genome subject to purifying selection, the total is still only about 10%, leaving 90% as neutral.

We have also known for a long time that most RNA transcripts do not result in cytoplasmic messenger RNAs (Salditt-Georgieff and Darnell JE Jr. publised a paper in 1981 with the title "Further evidence that the majority of primary nuclear RNA transcripts in mammalian cells do not contribute to mRNA.") and specific transcripts in noncoding regions were described by the end of the 1980s.

The science blogosphere has been aflame for the last two days as scientists attempt to debunk this hype.  Those bloggers (many of whom are authors on the ENCODE papers) have provided excellent summaries of the issues surrounding the notion of junk DNA.  I have bookmarked several on delicious (tag: ongenetics/ENCODE) and some (mostly the same ones) are listed below.

To my mind, the biggest problem is that what is not news (that not all noncoding DNA is junk) has been allowed to eclipse what is news (that we have a vast trove of data that allows us to assess possible functions for all nucleotides).

Links:
http://genome.ucsc.edu/ENCODE/
The gateway to ENCODE data (through the UC Santa Cruz genome browser)

http://www.genome.gov/10005107
The ENCODE project web site.

http://www.nature.com/encode/
This is Nature's gateway to the literature.  It's a little (OK, a lot) gimmicky, so you probably want to just visit the tables of contents: Nature, Science, Genome Research.

The Finch and the Pea: ENCODE Media Fail
This blog post by Mike White is a survey of media hype documenting numerous errors resulting from the hype (or misplaced focus).

Encode (2012) vs. Comings (1972)
This blog post by T. Ryan Gregory presents a serious review of the concept of "junk DNA."

ENCODE: My [Ewan Birney's] Own Thoughts
Ewan Birney on his own blog.

A Neutral Theory of Molecular Function
This blog post by Michael Eisen "wrestles" with the idea of junk DNA.
I want to end by pointing out that there are lots of people (me and my group included) who have already been wrestling with this issue, with lots of interesting ideas and results already out there. From an intellectual standpoint I’d like to particularly point out the influence the writings of Mike Lynch have had on me – see especially this.
ENCODE: The Rough Guide to the Human Genome
Ed Yong's post (at Discover Magazine), has been revised in the last day or so to be more cautious about the hype.

Cryptogenomicon: ENCODE says what?
This post by Sean Eddy makes the points that "The human genome has a lot of junk DNA," that "Noncoding DNA is part junk, part regulatory, part unknown," that "ENCODE’s definition of 'functional' includes junk" and that "Evolution works on junk."  His post has dozens of comments, mostly from experts in the field.

Finally, a few screen shots from Twitter in the last few days:
Reaction to ENCODE media hype on Twitter ranged from blind propagation to harsh criticism.