View Full Version : East Asian teeth, hair, and smaller breasts due to SNP 370A in gene EDAR 30-35kya

02-17-2013, 07:38 PM
Instead of quoting a bunch of news articles, I'm just going to link all the relevant literature to what's come out.

First, a tiny bit of background about the gene in question: http://en.wikipedia.org/wiki/EDAR

Essentially, EDAR is a growth factor receptor.

The New York Times has a good article on the paper - http://www.nytimes.com/2013/02/15/science/studying-recent-human-evolution-at-the-genetic-level.html

As does Science - http://news.sciencemag.org/sciencenow/2013/02/sweaty-human-evolution-through-a.html

This paper is based on the principles of another paper from the same lab (Pardis Sabeti's lab). The idea is that we can start finding more significant mutations like this in human evolution (the article is in Cell, so it's limited access).

Grossman et al., 2013. "Identifying Recent Adaptations in Large-Scale Genomic Data." http://www.cell.com/abstract/S0092-8674%2813%2900087-1

This paper, in conjunction with the accompanying paper on EDAR, represents a decisive shift for the field of evolutionary genomics, moving from hypothesis-driven to hypothesis-generating science. We further provide a comprehensive list of candidate adaptive mutations driving recent human selective sweeps that lay the foundation for myriad future functional studies. The data from the 1000G Project, along with functional annotations, are available on a genome-wide browser, together with software to compute CMS on any data set (http://www.broadinstitute.org/mpg/cms). In the years ahead, unprecedented data availability and collaborations across multiple disciplines from molecular, developmental, and computational biology to history and anthropology, promise to bring key recent events that have shaped our species to light.

Finally, the actual article - Kamberov et al., 2013. "Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant." http://www.cell.com/retrieve/pii/S0092867413000676

Unfortunately, it's also in Cell and limited access. Here's an excerpt:

Pleiotropic Effects and Potential Selective Forces Favoring the 370A Allele

Our study provides evidence that 370A was selected in East Asia, but the question of which of its observed pleiotropic phenotypes were adaptations and which were exaptations remains. One possibility is that selection favored individuals with an increased number of eccrine glands. A high density of eccrine glands is a key hominin adaptation that enables efficient evapotraspiration during vigorous activities such as long-distance walking and running (Carrier et al., 1984; Bramble and Lieberman, 2004). An increased density of eccrine glands in 370A carriers might have been advantageous for East Asian hunter-gatherers during warm and humid seasons, which hinder evapotranspiration.

Geological records indicate that China was relatively warm and humid between 40,000 and 32,000 years ago, but between 32,000 and 15,000 years ago the climate became cooler and drier before warming again at the onset of the Holocene (Wang et al., 2001; Yuan et al., 2004). Throughout this time period, however, China may have remained relatively humid due to varying contribution from summer and winter monsoons (Sun et al., 2012). High humidity, especially in the summers, may have provided a seasonally selective advantage for individuals better able to functionally activate more eccrine glands and thus sweat more effectively (Kuno, 1956). To explore this hypothesis, greater precision on when and where the allele was under selection—perhaps using ancient DNA sources—in conjunction with more detailed archaeological and climatic data are needed.

Alternatively, another phenotype, such as mammary gland branching or fat pad size could have been adaptive. The increased branching of 370A mouse mammary glands and the importance of mammary tissue in evolutionary fitness (Anderson et al., 1983; Oftedal, 2002) make this organ an interesting candidate. Alterations in gland structure have been reported to disrupt lactation in mice (Ramanathan et al., 2007), suggesting a functional consequence for this change. Unfortunately, it is not possible to assess mammary gland branching in living humans, highlighting the importance of animal models. Reports of smaller breast size in East Asian women (Maskarinec et al., 2001; Chen et al., 2004) are notable in light of the effects of 370A on fat pad size and the importance of breast morphology in human mate preference (Furnham et al., 1998, 2006; Dixson et al., 2011). Further analysis of the functional implications of 370A in the mouse and development of methods to assay these phenotypes in humans are critical to evaluate such hypotheses and also to analyze additional potential 370A phenotypes yet to be investigated, such as those linked to differential susceptibility to respiratory disease (Clarke et al., 1987; Mauldin et al., 2009).

In light of 370A’s pleiotropy, it is possible that selection acted on multiple traits. The tendency to seek a single driving character is underlain by the perception that pleiotropic changes are inherently disadvantageous. Evolution is believed to proceed primarily through mutations in gene regulatory regions rather than exons because this reduces pleiotropic effects (King and Wilson, 1975; Stern, 2000; Carroll, 2008). From the perspective of this model, a specific effect of 370A’s pleiotropic consequences was favored under the conditions present in East Asia and conferred an advantage with other neutral or deleterious traits hitchhiking along with the selected trait. However, the large coefficient of selection on 370A contrasts with the relatively modest magnitude of structural changes on any one affected trait and suggests alternative interpretations. One possibility is that the effects of 370A were magnified by coselection on another variant. For example, a coding variant of the related EDA2R gene affects human hair and has swept to fixation in East Asia (Sabeti et al., 2007; Prodi et al., 2008).

Alternatively, it could be precisely the pleiotropic nature of 370A that allowed multiple distinct selective forces to act on this variant over its long history, when many of the postulated selective pressures such as temperature and humidity changed dramatically. The fact that EDAR acts mostly on ectodermal appendages and that the phenotypic effects of the 370A allele are not extreme reduces the costs of pleiotropy and would facilitate this process. Thus, what were initially neutral changes in some appendages driven by 370A would gain adaptive significance in the face of new selective pressures. It is worth noting that largely invisible structural changes resulting from the 370A allele that might confer functional advantage, such as increased eccrine gland number, are directly linked to visually obvious traits such as hair phenotypes and breast size. This creates conditions in which biases in mate preference could rapidly evolve and reinforce more direct competitive advantages. Consequently, the cumulative selective force acting over time on diverse traits caused by a single pleiotropic mutation could have driven the rise and spread of 370A.