One thing we discussed at the ScienceBlogging09 meeting in London in August was the relationship between blogging and more formal scientific communications. Henry Gee suggested that blogs are for half-baked ideas, that can then be criticized in the blogospheric oven before being let out into the formal literature in the knowledge that the idea has been heated through, with a nice glazing applied. It’s odd, then, to read something in the formal literature that is less well baked than most blog posts.
The piece in question is a News and Commentary article in the latest Heredity titled “Sequencing one sex or the other has to be justified: Gender genomics and equality”. The authors want to argue that we should pay attention to the sex of the individuals we sequence. Why? Well…
because, for instance, recent reports on the molecular basis of social complexity in honeybees (Apis mellifera) highlight a critical relevance of sex-specific genomics by exploring the biochemical mechanisms of the differences between the contribution of females (Vergoz et al., 2007) or males (Mattila and Seeley, 2007) to cooperative behaviour within the hive.
So the genetic structure of a colony can affect the colony. Genotype affects phenotype, so this is no surprise. But how does that affect the DNA sequence? We aren’t told. The nearest we get it this, later in the article:
Genomics has only begun to scratch the surface in determining how interactions among genes and gene products influence the genotype, and it seems plausible that such interactions could differ between males and females.
Influence the genotype? That would be news. What references do they give? Um, none. Now, we know that retrotransposons can flit around and create all sorts of mayhem, but that’s hardly systematic. I think it’s a stretch to say that they are a major problem, even more so that there would be a sex biased difference.
Let’s sit down and talk this through carefully so we can see what the authors are suggesting. Sequencing genomes means finding the sequence of the DNA of a representative individual (or a consensus of several individuals) of a species. If there is no difference between sexes, it doesn’t matter which sex you take – the genome will be the same. Are there differences? Well, in humans we know that there are differences between the sex chromosomes, but this is why the human genome project sequenced both the X and Y chromosomes. So it looks like the sequencers did give some thought to this. What about the other chromosomes? Well, as these are inherited randomly from both parents, there shouldn’t be any sex-biased difference in sequence.
But despite all this, there may be some bias in the choice of sex. After all:
the honeybee DNA was taken from several drones derived from a single queen, which resulted in the sequence of the haploid male genome.
They sequenced a male, the naughty chauvinists!
Oh, wait a moment. Let’s think like (asexual) biologists. Like many hymenoptera, honeybees are haplo-doploid, so males are haploid and females are diploid1. Sequencing a haploid individual makes sense, because you only have one copy of each sequence to worry about: you don’t need to worry about which copy of a sequence you are dealing with. And, because the genes are passed on randomly from the mother, we know that taking several males will give us the mother’s genotype. In other words, in this case it makes sense to sequence males.
Overall, the cry to be careful about which sex is sequenced is silly on biological grounds – we know enough about sex determination to take care, and the authors don’t present any evidence that there is a problem (go and check – it’s really wooly). But I’ve left the best ’til last. The authors ask “Why does such gender genomics matter?” and answer (the emphases are mine)…
Because our generalizations are only as good as the model systems on which they are based. For many years, the model for virtually all processes in humans and non-humans alike was the male, with females representing a special case; an exception to be studied after the representative subjects had been described. In medical research, this paradigm led to the disproportionate use of male subjects, whether rodents, monkeys or humans, in basic research on anatomy and physiology as well as studies of disease, an imbalance that has only been addressed in the last few decades (Zuk, 2002). In our human society, it has meant that women in atypical roles are often undervalued compared with their male counterparts, leading to relatively slower advancement for women with equal qualifications.
Seriously? The reason sexism exists is because science treated males as the norm? We have that much power? Or is this utter tosh?
If this article had been a post on a blog with a reasonable number of readers, I’m sure they would have pointed out the problems with the arguments. The half-baked nature is better accepted, and the authors would have been able to refine their arguments, so that they made more sense. But for a published article, I would expect the authors to have done this themselves. There are three authors, so surely one of them would have said “hang on a moment…”.
I worry about the effect this sort of article has on gender equality. Radical feminism already has a reputation for taking things too far, and even if it may be partly deserved, overall I think we do have to treat problems of discrimination seriously. But that doesn’t mean every aspect of science is tainted with sexism: we have evidence which suggests it doesn’t affect refereeing (at least on average!), for example. And worrying about every possible problem is counter-productive: we end up wasting time balancing non-existent inequalities, when we could be concentrating on the problems that do matter. That’s not so say that e shouldn’t look at whether the choice of individuals to sequence is sexist, but rather that we should still do it critically. If the best argument you can come up with is so poorly done that bits of the cake are still frozen, then perhaps there isn’t anything there. Just quietly announce it as a success, and move on to look at the next potential problem. the pessimist in me says that you’ll find a real problem eventually. And then I’ll be happy to leap in and support doing something about it – whether it is symbolic (e.g. making sure that we don’t just celebrity sequence middle-class males), or more down to earth.
Reference
Hauber M.E., Sewell, M.A. and Zuk, M. (2008). Sequencing one sex or the other has to be justified: Gender genomics and equality. Heredity 101: 395; doi:10.1038/hdy.2008.83
1 Actually, it’s a bit more complicated than this. Honeybees have a system called complementary sex determination. They have a sex determining locus. If an individual is heterozygous, i.e. they have two different alleles at the locus, they become female. If they they only have one allele, they become male. this can happen if they are halpoid (“hemizygous”), with only half a genome, or if they are diploid but both copies of the sex determining gene are the same.
If they were talking about sequencing the transcriptome or epigenome, then I could see the point of taking gender into account, but not when sequencing the actual genome.
“Seriously? The reason sexism exists is because science treated males as the norm? We have that much power? Or is this utter tosh?”
This isn’t the reason that sexism exists (I mean WTF? Although the reverse is/was arguably true), but I think that it can be a problem in certain fields of medicine. If all your work on, say, diabetes is done in males, then you are not going to see any potential fluctuations during the female menstrual cycle, for example. And I’m sure I read somewhere that this kind of thing has happened in the past (yup, Cath applies her usual research and citation standards).
Fortunately I think we’ve come a long way towards a more inclusive model of science – for example I recently helped a PI to submit an NIH proposal for a clinical trial, and we had to write a statement on plans for the inclusion of women.
But genome sequencing? Really?
I think science treats males as the norm because sexism exists. Look at (not so) old anatomy books, especially with respect to genitals.
Yeah, as if I’m gonna click that link at work, Richard.
Genomics has only begun to scratch the surface in determining how interactions among genes and gene products influence the genotype, and it seems plausible that such interactions could differ between males and females.
I think the key word here is plausable which is what, at least I, use when I think it seems resonable but I haven’t found one single reference or evidence to help me back the case up. But it sounds reasonable and I would like to further investigate the genes and gene products that influence the genotype.
To be fair, as far as I know, it isn’t known how the transcription/translation is different in male vs female genotypes – if we talk about allele expression. I guess it could be argued though that the genotype and sex would make the difference in phenotype, theoretically a set of twins with identical genome but one has XY and one XX. Would they “look alike”? Or rather I guess what the authors might mean is that the XY will have different interactions of the genes and proteins due to XY compared to the expression of the same alleles in the XX.?! (Trying to understand what they really mean here. Is that what they mean? Since I am neither a human geneticist or so, I am out-side my field here… just thinking and asking questions.)
“the model for virtually all processes in humans and non-humans alike was the male,”
I think this would be due to the reasons of sexism since I think that you would study the “higher” of the two beings, man and woman. As a result it is also easier to study men, since they have stable levels of hormones (apart from being angry with testosterone) after the teenager phase is over. Women, which have been the key argument for why women weren’t part of the medical testing, can get pregnant and really, since women are “as men but lesser” then if it is good enough for the man, it is certainly good enough for the woman.
“In medical research this paradigm led to the disproportionate use of male subjects,..//..addressed in the last few decades (Zuk, 2002).”
Interestingly, I have only worked with female mice. Are you telling me that most of them were male in the previous years? Huh, I had no idea about that. I knew about the humans and monkeys… On a side note the lab we order from offer only female mice after 8 weeks of age. Before that they have both sexes, and the males are on average $0.25 cheaper per mouse. Just as an information ….
It’s anatomical, Cath, not pornographic.
That’s what they all say.
p.s. it looks like people from other time zones has gone… why is it always just us left?!
we’re hardcore.
Fancy a pint?
Ooh yes please.
[sudden appearance] What is all this about beer?
I don’t know about you lot, but I will be at the Cedar Cottage in Vancouver in about 45 minutes. Just finishing off some work before I go.
You are very welcome to join me! Scramble your private jet, we’ll be there a couple of hours at least.
Excellent. See you there.
xx
Sorry Bob, we hijacked your thread.
He’s never had so many comments.
(
or offers of sex and beer)Thanks, Richard, but all you offered were pictures.
[Desperate scramble for Bob’s serious point] The business at the end about sexism is tosh, at least when applied to the foregoing. And as far as I can see from this distance (Cromer being a long way from anywhere, much) is a certain terminological inexactitude. It’s a long way between ‘genotype’ and ‘phenotype’, and I wouldn’t start from here, particularly as all sorts of things go on in between such as imprinting, transcription, insertion, deletion, recombination and (_noblesse oblige_) the release of calcium from intracellular stores (in the town hall, if wet).
Bob, I think it’s your round.
And Richard, put away those dirty pictures. It’s neither big nor clever. Well, clever, anyway. Richard? Richard? Oh, he’s in the
cottagegents.Penny seemed keen to see them anyway, Henry.
Just saying.
bq. It’s a long way between ‘genotype’ and ‘phenotype’,
Quite, which is why it’s so odd to insist on looking at the genotype. Especially in a genetics journal – you would have thought someone would have noticed.
Your usual Babycham?
It all comes back to scientists being
scepticskeptical. Peer review is far from perfect (especially when it involves rejection of my hard work), but it’s the standard we’re stuck with at the moment.Just because an article is published, doesn’t make what is contained within it God’s holy truth. Unless, of course, it’s published in one of God’s many holy books.
I agree Mike. I just wish the authors had shown some scepticism about what they had written, and not demonstrated their apparent ignorance of basic genetics in a (usually rather good) genetics journal.
Hey, I’d love a Babycham.
Where were all you guys? I waited and waited and waited.
Sorry, I got held up at Hawaii. Something about flight clearance.
Had a nice evening chatting up my pilot, though.