Natural selection and the human genome -- the last 10,000 years

Many researchers have been interested in combing the human genome for evidence that natural selection shaped modern humans. The idea is that selection would have favored those of our ancestors who were best able to adapt to changing environments over the past 100,000 or even 10,000 years, as they began to wend their way into the entire diversity of the world's environments, most of them very different from our African savanna homeland. How could we not have faced selective environments? And, look at us--at how different peoples native to different continents appear! How else but by natural selection?

And what about the effects of dense, settled populations after the invention of agriculture, including the strong selective force of disease, which could more easily spread with people living close together? Not only that, but in terms of hundreds of thousands of sequence variants across the genome that were chosen for genotyping for their variation rather than function (most probably functionless or without effect on fitness), it should be easy to identify genome regions that show evidence of selection, by virtue of manifesting greater than average difference among world regions.

The availability of large sets of data on variation in the genome, from populations across the globe, as well as methods for doing large-scale analysis of these data has meant a field day for people interested in this question. They have developed and applied a number of methods for the purpose, to distinguish the statistical chaff from the selective grain: when one does many thousands of tests across the genome one is bound to find 'signals' that arise just by the chance aspects of population sampling. A number of reports have come from these studies, some finding that human evolution is speeding up, and others finding evidence of strong selection at a few sites in the genome. Some claim many positive findings, others that the overall amount of such evidence, given the expectation, is rather small.

A paper in the June issue of PLoS Genetics by Jonathan Pritchard at the University of Chicago and collaborators, reports that selection has not been nearly as strong as many people expected. These results are not a total surprise given that most traits are affected by many genes, that environments change rapidly enough that one era's successful adaptation may be another's maladaption, and that a fundamental survival tactic of all organisms is the ability to adapt behaviorally to changing environments as they happen. Humans above all organisms have the added benefit of culture, which can buffer ecological changes. We make fire, and clothes, to protect against the cold, we invent weapons to substitute for weak teeth in hunting prey, and we have language to organize group responses to threats, the need for food and shelter, and so on.

That doesn't remove humans from the effects of selection, and crowded, permanent agricultural settlement might be particularly vulnerable to new forces, such as infectious pathogens.

But even then, and even if selection is particularly strong (and a 1% selective advantage, often literally too small to be detectable from samples at any given time, is considered strong), it may be difficult to detect selection at the gene level. If many genes affect a trait, and given the clear fact that in a population there are many sequence variants at any gene (and the nearby parts of DNA that regulate its cellular usage), the impact of selection is distributed across these many possibly advantageous variants.

What is favored or disfavored are combinations of variants at many genes. Individually, they have rather trivial effect. And most selection is weak, at least in this sense, as we've written before. When the net advantage of a variant is very small, its frequency changes largely by chance (genetic drift). As a result, when regions of the world are compared, there is usually no difference between the pattern of random markers and genes that have been affected by selection.

Occasionally, a variant has a strong effect in its current environments, and can be quickly advanced in frequency (sickle cell as protection against malaria is one of only a handful of truly convincing examples). But such variants are usually very rare, and won't be seen in the kinds of the small population samples that have been used for geographic studies of human variation. A rare variant that is quickly favored will rise to high frequency and then its effect on the favored trait will become close to average. But at least the pattern of variation in the gene and its nearby chromosome region will show less variation within its source population, and greater differences between populations, than is typical of the rest of the genome. That is the kind of signal people hope to find, but that seem for reasons just described, to be rare in humans.

So, even from a strongly darwinian point of view, 'signatures' of selection will be expected to be weak, as the authors of this paper found. Darwin's work was about phenotypes (traits) not genotypes. The focus on genes may be showing that that is the correct viewpoint in which to understand evolution, whether selection is strong or weak, persistent or occasional.

How long would it take to walk to the ends of the Earth?

"Who started walking out of Africa? Not everybody walked. Very few people walked, and they walked to the ends of the Earth. The geneticists now have found that the people who migrated had a particular gene, and this gene makes you a risk-taker, a wanderer. Bipolarity is an extreme version of this gene, and the people who migrated, they had this gene."

This is a quote from Indian political economist, Deepak Lal, on the BBC radio show, The Forum, which aired 05/24/09. Lal went on to say that the people who inherited this gene for risk-taking are now ethnic minorities, which explains why they tend to "punch above their weight".

But the people who migrated out of Africa are ancestors of us all. If they had a gene 'for' risk-taking, all of us would have it, not just today's ethnic minorities. And, it can't be argued that for genetic reasons ethnic minorities tend to succeed more often than majority populations because the minorities are or were majorities somewhere at some time.

It's amazing how misguided smart people can be about genetics and population history. Granted Lal is an economist, not a population geneticist or anthropologist-- but he spoke so authoritatively! Darwinian scenarios, of the BS as well as plausible variety, are so easy to put forth with an air of confidence! But, is this all air, or does it actually matter when people get it so wrong? We suggest that it does for a number of reasons because it happens in many contexts, with ramifications, not just on BBC radio programmes.

First, the idea of a gene 'for' risk-taking has been reported, but the original study has been difficult to replicate, in part because it's difficult to define risk-taking, and in part because genes 'for' behavior have been quite elusive. Populations considered to be high risk-takers or violent by some, with a high frequency of the DRD4 mutations originally associated with risk-taking, might be considered to be pacific by others, for example. So, this trait is, like most complex traits, difficult to define and genes 'for' it difficult to confirm. If one thinks about genetic mechanisms, many genes would contribute to such traits, and they would be very culture-specific or their manifestation would be, at least.

Second, genes 'for' bipolarity, again as for all complex traits, have not been confirmed. Mapping genes making major contributions to psychiatric disorders has been very problematic, at best. Some candidates have been found, but even they generally account for only a small fraction of the instances.

Third, ethnic minorities are only such at certain times and places.

Fourth, can we really conclude that ethnic minorities are all feisty? It's funny how people with guns, money, or power can seem so much more adventurous than those who haven't the same assets.

These simple (or is it simplistic?) Darwinian arguments reflect incredibly naive population biology. Basically, nobody 'walked out of Africa' in the alleged sense. People did not have travel posters or travel agents. They might go upstream or 'over there' to find game or plants they liked to eat. If nobody was living there (or only brute Homo erectines), they might decide to kick them out and take over a nice campsite. Nobody ever heard of the ends of the earth! They did not know there were island paradises in the Pacific to go vacation at.

Young adults would pair up and move to better pastures, perhaps to get away from their annoying parents or pests in their little hunter-gatherer bands. They would, however, generally stay in touch--not go too far, because family was everything for social survival (and mates in the next generation). Gradual expansion would be on foot and in a sense by everyone, going over the next hill for open territory. Nobody would know they were going anywhere!

Each generation, village exogamy (kin-based mating rules) would mean that the 'explorers'' children would have to return to their former hearth and home to find mates. There would be large amounts of inter-village gene flow, back and forth, each generation.

It is possible that among those who chose to pop over the hill, those more inclined would have some slightly increased probability of doing that. But in the overall scheme of things, genetic drift and other kinds of chance would have watered down any such signal.

The genetic data clearly show that the farther from Africa people are, the smaller the subset of 'African' genetic variants they carry. This does not mean that they purified African adventure genes, and those in Tierra del Fuego aren't pure adventurers, nor less so than the Bantu marauders who captured each other in wars and sold the victims into slavery (unless there is an adventure gene in the slaves that made them turn themselves in?)

In historic times, and in invasions, hordes of armies or boatloads of pilgrims were forced to travel and settle elsewhere, in large numbers. They were not selected based on Indiana Jones genes.

We'll be a lot better off in evolutionary reconstructions, especially as regards behavior which clearly reflects social biases of the authors, if we temper our view based on a realistic understanding of the demographic chaos that is life!