Searching for the genetics of identical twinning

3 minute read

This week, Nature is carrying a news feature by David Cyranoski, which profiles Bruno Reversade, a geneticist trying to find genetic causes of identical twinning in humans. This is not very easy to do, since twinning is rare and sporadic, and does not appear to be heritable in most pedigrees. Still, there are odd cases – the towns scattered around the world that seem to have too many twin births, or the family that has a lot of cases.

For example:

Two years ago he travelled to Jordan to collect saliva samples from members of a family with 15 pairs of monozygotic twins. The family tree fits a pattern in which a dominant gene one that would cause monozygotic twinning even if only one copy is present is on one of the 22 autosomal chromosomes. But to make the hereditary pattern work, the gene must have 'variable penetrance', such that some women would not bear monozygotic twins even though they carried a copy of the gene. "Variable penetrance is of course a 'black box'," says Reversade. "Why don't we see more twins?" One reason, he suggests, is that some twins 'vanish' meaning that at least one of the two dies during pregnancy.

Still, there are an awful lot of towns in the world, and an awful lot of families. A single case that produces a lot of twin births is going to happen once in a great while by chance.

When people find out I have twins, the most common question is “Do they run in your family?” And well, for identical twins it doesn’t really matter if you have twins in your family. That’s not to say there couldn’t be genetic factors, but it does imply that such factors must have a very low penetrance (meaning that twinning is a very unlikely result of carrying an allele). That makes twinning very different from a Mendelian trait, in which the causal alleles have a high penetrance – for example, all homozygotes for a CF risk allele will develop CF.

On the topic of the twins “vanishing”, the next paragraph contains some astounding numbers:

According to a widely cited estimate by Charles Boklage, a behavioural and developmental biologist at East Caroline University in Greenville, North Carolina, at least 12% of natural conceptions will produce twin embryos. Both twins come to term in only 2% of those pregnancies. A singleton is born around 12% of the time, and in the vast majority of cases both embryos are lost, often without the pregnancy ever being noticed.

I don’t doubt those – humans have a very high rate of spontaneous embryonic and fetal losses. Boklage’s numbers imply that losses in twin conceptions are a lot higher than otherwise, but both kinds are high compared to most mammals. That’s an evolutionary mystery – why don’t we do better carrying conceptions to term?

After this, the article goes on to discuss some generally questionable evolutionary ideas about twinning in humans. I say “questionable” because the article implies that humans twin “often,” calling us “one of the most proficient mammalian species at monozygotic births.” The quoted scientists seem to be unaware that monozygotic twinning occurs in chimpanzees at the same frequency as in humans; they also seem oblivious to the fact that dizygotic and monozygotic twinning have similar evolutionary costs and benefits for the mother. Captive chimpanzees have higher dizygotic twinning rates than humans, but neither chimpanzees nor humans are exceptional for primates in their twinning rates.

Yes, the article ends with a grab-bag of twin stuff, including the story about epigenetic and copy number differences between twins, and that town in Brazil where Mengele supposedly dosed the water with twin-juice.