Tag: Genetics

Mouse fidelity comes down to the genes

Posted on by Razib Khan

While birds tend to be at least nominally monogamous, this is not the case with mammals. This strikes some people as strange because humans seem to be monogamous, at least socially, and often we take ourselves to be typically mammalian. But of course we’re not. Like many primates we’re visual creatures, rather than relying in smell and hearing. Obviously we’re also bipedal, which is not typical for mammals. And, our sociality scales up to massive agglomerations of individuals.

How monogamous we are is up for debate. Desmond Morris, who is well known to many from his roles in television documentaries, has been a major promoter of the idea that humans are monogamous, with a focus on pair-bonds. In contrast, other researchers have highlighted our polygamous tendencies. In The Mating Mind Geoffrey Miller argues for polygamy, and suggests that pair-bonds in a pre-modern environment were often temporary, rather than lifetime (Miller is now writing a book on polyamory).

The fact that in many societies high status males seem to engage in polygamy, despite monogamy being more common, is one phenomenon which confounds attempts to quickly generalize about the disposition of our species. What is preferred may not always be what is practiced, and the external social adherence to norms may be quite violated in private.

Adducing behavior is simpler in many other organisms, because their range of behavior is more delimited. When it comes to studying mating patterns in mammals voles have long been of interest as a model. There are vole species which are monogamous, and others which are not. Comparing the diverged lineages could presumably give insight as to the evolutionary genetic pathways relevant to the differences.

But North American deer mice, Peromyscus, may turn to be an even better bet: there are two lineages which exhibit different mating patterns which are phylogenetically close enough to the point where they can interbreed. That is crucial, because it allows one to generate crosses and see how the characteristics distribute themselves across subsequent generations. Basically, it allows for genetic analysis.

And that’s what a new paper in Nature does, The genetic basis of parental care evolution in monogamous mice. In figure 3 you can see the distribution of behaviors in parental generations, F1 hybrids, and the F2, which is a cross of F1 individuals. The widespread distribution of F2 individuals is likely indicative of a polygenic architecture of the traits. Additionally, they found that some traits are correlated with each other in the F2 generation (probably due to pleiotropy, the same gene having multiple effects), while others were independent.

With the F2 generation they ran a genetic analysis which looked for associations between traits and regions of the genome. They found 12 quantitative trait loci (QTLs), basically zones of the genome associated with variation on one or more of the six traits. From this analysis they immediately realized there was sexual dimorphism in terms of the genetic architecture; the same locus might have a different effect in the opposite sex. This is evolutionarily interesting.

Because the QTLs are rather large in terms of physical genomic units the authors looked to see which were plausible candidates in terms of function. One of their hits was vasopressin, which should be familiar to many from vole work, as well as some human studies. Though the QTL work as well as their pup-switching experiment (which I did not describe) is persuasive, the fact that a gene you’d expect shows up as a candidate really makes it an open and shut case.

The extent of the variation explained by any given QTL seems modest. In the extended figures you can see it’s mostly in the 1 to 5 percent range. In Carl Zimmer’s excellent write up he ends:

But Dr. Bendesky cautioned that the vasopressin gene would probably turn out to be just one of many that influence oldfield mice. Though it is strongly linked to parental behavior, the vasopressin gene accounts for 6.7 percent of the variation in nest building among males, and only 2.9 percent among females.

The genetic landscape of human parenting will turn out to be even more rugged, Dr. Bendesky predicted.

“You cannot do a 23andMe test and find out if your partner is going to be a good father,” he said.

Sort of. The genetic architecture above is polygenic…but not incredibly diffuse. The proportion of variation explained by the largest effect allele is more than for height, and far more than for education. If human research follows up on this, I wouldn’t be surprised if you could develop a polygenic risk score.

But I don’t have a good intuition on how much variation in humans there really is for these sorts of traits that are heritable. I assume some. But I don’t know how much. And how much of the variance in behavior might be explained by human QTLs? Humans don’t lick or build nests, or retrieve pups. Also, as one knows from Genetics and Analysis of Quantitative Traits sexually dimorphic traits take a long time to evolve. These are two deer mice species. Within humans there may not have been enough time for this sort of heritable complexity of behavior to evolve.

There are a lot of philosophical issues here about translating to a human context.

Nevertheless, this research shows that ingenious animal models can powerfully elucidate the biological basis of behavior.

Citation: The genetic basis of parental care evolution in monogamous mice. Nature (2017) doi:10.1038/nature22074

Women hate going to India

Posted on by Razib Khan


For some reason women do not seem to migrate much into South Asia. In the late 2000s I, along with others, noticed a strange discrepancy in the Y and mtDNA lineages which trace one’s direct male and female lines: in South Asia the male lineages were likely to cluster with populations to the north an west, while the females lines did not. South Asia’s females lines in fact had a closer relationship to the mtDNA lineages of Southeast and East Asia, albeit distantly.

One solution which presented itself was to contend there was no paradox at all. That the Y chromosomal lineages found in South Asia were basal to those to the west and north. In particular, there were some papers suggesting that perhaps R1a1a originated in South Asia at the end of the last Pleistocene. Whole genome sequencing of Y chromosomes does not bear this out though. R1a1a went through rapid expansion recently, and ancient DNA has found it in Russia first. But in 2009 David Reich came out with Reconstructing Indian population history, which offered up somewhat of a possible solution.

What Reich and his coworkers found that South Asia seems to be characterized by the mixture of two very different types of populations. One set, ANI (Ancestral North Indian), are basically another western or northwestern Eurasian group. ASI (Ancestral South Indian), are indigenous, and exhibit distant affinities to the Andaman Islanders. The India-specific mtDNA then were from ASI, while the Y chromosomes with affinities to people to the north and west were from ANI. In other words, the ANI mixture into South Asia was probably through a mass migration of males.

But it’s not just Y and mtDNA in this case only. A minority of South Asians speak Austro-Asiatic languages. The most interesting of these populations are the Munda, who tend to occupy uplands in east-central India. Older books on India history often suggest that the Munda are the earliest aboriginals of the subcontinent, but that has to confront the fact that most Austro-Asiatic language are spoken in Southeast Asia. There was no true consensus where they were present first.

Genetics seems to have solved this question. The evidence is building up that Austro-Asiatic languages arrived with rice farmers from Southeast Asia. Though most of the ancestry of the Munda is of ANI-ASI mix, a small fraction is clearly East Asian. And interestingly, though they carry no East Asian mtDNA, they do carry East Asian Y. Again, gene flow mediated by males.

The same is true of India’s Bene Israel Jewish community.

A new preprint on biorxiv confirms that the Parsis are another instance of the same dynamic: The genetic legacy of Zoroastrianism in Iran and India: Insights into population structure, gene flow and selection:

Zoroastrianism is one of the oldest extant religions in the world, originating in Persia (present-day Iran) during the second millennium BCE. Historical records indicate that migrants from Persia brought Zoroastrianism to India, but there is debate over the timing of these migrations. Here we present novel genome-wide autosomal, Y-chromosome and mitochondrial data from Iranian and Indian Zoroastrians and neighbouring modern-day Indian and Iranian populations to conduct the first genome-wide genetic analysis in these groups. Using powerful haplotype-based techniques, we show that Zoroastrians in Iran and India show increased genetic homogeneity relative to other sampled groups in their respective countries, consistent with their current practices of endogamy. Despite this, we show that Indian Zoroastrians (Parsis) intermixed with local groups sometime after their arrival in India, dating this mixture to 690-1390 CE and providing strong evidence that the migrating group was largely comprised of Zoroastrian males. By exploiting the rich information in DNA from ancient human remains, we also highlight admixture in the ancestors of Iranian Zoroastrians dated to 570 BCE-746 CE, older than admixture seen in any other sampled Iranian group, consistent with a long-standing isolation of Zoroastrians from outside groups. Finally, we report genomic regions showing signatures of positive selection in present-day Zoroastrians that might correlate to the prevalence of particular diseases amongst these communities.

The paper uses lots of fancy ChromoPainter methodologies which look at the distributions of haplotypes across populations. But some of the primary results are obvious using much simpler methods.

1) About 2/3 of the ancestry of Indian Parsis derives from an Iranian population
2) About 1/3 of the ancestry of Indian Parsis derives from an Indian popuation
3) Almost all the Y chromosomes of Indian Parsis can be accounted for by Iranian ancestry
4) Almost all the mtDNA haplogroups of Indian Parsis can be accounted for by Indian ancestry
5) Iranian Zoroastrians are mostly endogamous
6) Genetic isolation has resulted in drift and selection on Zoroastrians

The fact that the ancestry proportion is clearly more than 50% Iranian for Parsis indicates that there was more than one generation of males who migrated. They did not contribute mtDNA, but they did contribute genome-wide to Iranian ancestry. There are wide intervals on the dating of this admixture event, but they are consonant oral history that was later written down by the Parsis.

So there you have it. Another example of a population formed from admixture because women hate going to India.

Citation: The genetic legacy of Zoroastrianism in Iran and India: Insights into population structure, gene flow and selection.
Saioa Lopez, Mark G Thomas, Lucy van Dorp, Naser Ansari-Pour, Sarah Stewart, Abigail L Jones, Erik Jelinek, Lounes Chikhi, Tudor Parfitt, Neil Bradman, Michael E Weale, Garrett Hellenthal
bioRxiv 128272; doi: https://doi.org/10.1101/128272

Sex bias in migration from the steppe (revisited)

Posted on by Razib Khan

Last fall I blogged a preprint which eventually came out as a paper in PNAS, Ancient X chromosomes reveal contrasting sex bias in Neolithic and Bronze Age Eurasian migrations. The upshot is that the authors found that there was far less steppe ancestry on the X chromosomes of Bronze Age Central Europeans than across the whole genome. The natural inference here is that you had migrations of males into territory where they had to find local wives.

But the story does not end there. Iosif Lazaridis and David Reich have put out a short not on biorxiv, Failure to Replicate a Genetic Signal for Sex Bias in the Steppe Migration into Central Europe. It’s short, so I suggest you read the note yourself, but the major issue seems to be that on X chromosomes ADMIXTURE in supervised mode seems to behave really strangely. Lazaridis and Reich find that there seems to be a downward bias of steppe ancestry. Ergo, the finding was an artifact.

Goldberg et al. almost immediately responded, Reply To Lazaridis And Reich: Robust Model-Based Inference Of Male-Biased Admixture During Bronze Age Migration From The Pontic-Caspian Steppe. Their response seems to be that yes, ADMIXTURE does behave strangely, but the overall finding is still robust.

With these uncertainties I do wonder if it’s hard at this point to evaluate the alternative models. But, we do have archaeology and mtDNA. What do those say? On that basis, from what little I know, I am inclined to suspect a strong male bias of migration.

Citation: Reply To Lazaridis And Reich: Robust Model-Based Inference Of Male-Biased Admixture During Bronze Age Migration From The Pontic-Caspian Steppe, Amy Goldberg, Torsten Gunther, Noah A Rosenberg, Mattias Jakobsson
bioRxiv 122218; doi: https://doi.org/10.1101/122218

Citation: Failure to Replicate a Genetic Signal for Sex Bias in the Steppe Migration into Central Europe, Iosif Lazaridis, David Reich, bioRxiv 114124; doi: https://doi.org/10.1101/114124