This guest post is by Stephan Schiffels (@stschiff) on his paper with Richard Durbin Inferring human population size and separation history from multiple genome sequences biorxived here
In our paper, we study genome sequences to learn about human history and how human populations are related to each other. Remarkably, we only need a few individuals for this, because once we look sufficiently many generations into the past, every single genome contains fragments from a very large number of ancestors. This means that given only two genomes, say one individual from Africa and one individual from Europe, we typically find shared fragments from common ancestors (great great … great grandparents) from 2,000 or more generations ago. This trace of shared segments in our genomes can be detected and enables us to make inference about human history.
A few years ago, Heng Li and Richard Durbin introduced the PSMC method which is based on estimating this shared common ancestry in a single diploid genome to infer population sizes. We now introduced a major extension to this approach, called MSMC (Multiple Sequentially Markovian Coalescent), which is able to find and date traces of shared ancestry across multiple genome sequences. This is generally a hard problem because of the complex way of how sequences relate with each other through recombination and mutation (see an excellent blog post by Adam Siepel). In our method, we therefore made a choice to focus only on the pair of segments which coalesce first, i.e. share the most recent common ancestor of all pairs. Because of ancestral recombinations, this changes along the sequences.
Consider again the example of an African and a European individual, each of them carrying two copies of a chromosome. In one part of their genomes, the most recent ancestor of any two chromosomes may be shared between the two European chromosomes, in other parts it may be shared between the two African chromosomes, and in some cases it may actually be found across a European and an African chromosome. The relative frequency of how often we observe each of the three cases, and the distribution of times to the most recent common ancestor, give information about when the separation happened, and how long it took for the ancestral people to part fully from each other. In the case of West-Africans and Europeans, we found that the two populations started to separate from each other (at least genetically) long before the known out-of-Africa emigration 50,000 years ago. And we see the same thing if we compare West-Africans to Asians or Americans instead of Europeans. We can also see clearly how ancestors of Native Americans separated from Asians around 20,000 years ago, consistently preceding the known first arrival of people in the New World around 15,000 years ago.
Our method can also estimate effective population size changes through time. One consequence of our approach to look only for the first common ancestor is that we can now look into the much more recent past than was previously possible with similar methods, such as PSMC. For example, we can now see a deep bottleneck in Native American ancestors around 15,000 years ago which fits with the separation and immigration history described above, and we can see recent expansions that are consistent with the spread of agriculture in Africa.
We believe that MSMC is a useful tool for estimating population history from whole genome sequences. But more ideas and development are still needed in the future to expand this approach to more genomes and to look into the past even more recently than 2,000 years ago, which is our current limit with MSMC. Closely related approaches are currently developed by Yun Song, Thomas Mailund and others, which will complement MSMC. This is a great time to work in this field, given that many more high quality individual genome sequences are being generated, and in many cases from populations that we have not covered at all in our paper. All of this will help to greatly expand our knowledge of human population history.