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-confusedious
P.S. This post is sticky, see below for what’s new.
Hello everyone,
Apologies, I have been away from the blog for a while as I have been finishing up my Master’s degree! I should be back to publishing regularly form this point forth.
Now, to the topic at hand.
An interesting piece appeared in the American Journal of Physical Anthropology this month relating to hybridisation between two holwer monkey species, and the difficulty of identifying these hybrids on visual characteristics alone (morphology). In short, the morphology of these hyrbidised individuals does not correspond directly with the level of admixture present in genetic terms. For example, an individual with, say, one parent that was a first generation hybrid and one that was a non-hybrid, will not exhibit a 25/75 split in its morphology; it is more likely to simply appear to be a typical member of the species that has contributed the most genetic material.
This finding is interesting when we consider the argument surrounding the possibility of interbreeding between species of Homo in the Middle and Late Pleistocene. In essence, from a genomic perspective interbreeding seems to have been very likely, with both Homo neanderthalensis and the still mysterious Denisova hominin having made measurable contributions to the modern human genome. On the other hand, fossil evidence of anything that could decidedly be called a hybrid is virtually non-existant (virtually as there are some odd crania about from the Late Pleistocene that have raised hybrid questions, for example ‘the child of Lagar Velho’). Considering what was found in the piece mentioned above (full citation below) this lack of fossil evidence actually seems rather logical (not that we were expecting to find an abundance to begin with), as any hybrid individuals of anything other than a first generation cross would be likely to resemble one parental species so greatly as to render any talk of hybridisation moot.
Are palaeoanthropologists chasing phantoms in looking for some kind of ideal hybrid? I say likely yes.
Full citiation:
Kelaita, M. A. and Cortés-Ortiz, L. (2012), Morphological variation of genetically confirmed Alouatta Pigra × A. palliata hybrids from a natural hybrid zone in Tabasco, Mexico. Am. J. Phys. Anthropol.. doi: 10.1002/ajpa.22196
Copy Number Variation in the Human Genome and its Role in Human Evolution
NOTE: Apologies, the images I have uploaded appear to be a little difficult to decipher on a black background. In order to make good use of them you may need to save them and open them in an image viewer. – Confusedious
Introduction
Following the completion of the human genome project in 2003 (Collins, Morgan, & Patrinos, 2003), and the technological advances in gene sequencing and mapping this project enabled (Watson, 2004), it became apparent that the human genome was host to great inter-individual and inter-population variation. While much of the work on human genetic diversity has focused upon variations at the nucleotide level, the so-named point mutations or single nucleotide polymorphisms (SNPs) (Freeman et al., 2006), researchers have also come to realise that polymorphisms of a larger scale are both relatively abundant and of importance in terms of phenotypic expression (Fu, Zhang, Wang, Gu, & Jin, 2010), flagging them as being of potential consequence to studies of human evolution (Zhang, Gu, Hurles, & Lupski, 2009). Prime among these larger scale polymorphisms are those known as copy number variations (CNVs), an umbrella term used to refer to the duplication or deletion of regions of DNA of variable length (from a few hundred base pairs to millions of base pairs), often with consequences for the products of the genes encoded within, and thus, observable impacts upon phenotype that can be considered to alter fitness (Freeman, et al., 2006; Zhang, et al., 2009).
While much of the work on CNVs to date has focused upon simply identifying sites of variation in the human genome and comparing these loci in terms of frequency and positioning on chromosomes between individuals of differing geographic ancestry for ‘genealogical’ purposes (Chen et al., 2011; Li et al., 2009; Redon et al., 2006), or for the investigation of pathophysiologies (Horev et al., 2011; Lee & Lupski, 2006; Mills et al., 2011), this essay shall focus upon the evolutionary implications of CNVs in the human genome from both an inter and intra specific position. In order to better place CNVs in an evolutionary context, the first section of this essay shall focus upon how these variations occur and produce phenotypic changes that can be of evolutionary consequence. Following this, an analysis of CNVs between Homo sapiens and our nearest extant relative, Pan troglodytes, shall be assessed for what they can tell us about the broader evolutionary history of hominins. Moving to a focus on relatively recent human evolutionary history, the role of CNVs in adaptation to the unique problems faced by post-Neolithic revolution populations shall be explored, namely the problems of dietary change and pathogen burden as a result of higher density living. In closing, the principal difficulties in the interpretation of CNVs in the context of human evolution shall be highlighted and predictions about the findings of future studies shall be made.
How Copy Number Variations Arise and Produce Phenotypic Change
Prior to the completion of the human genome project, CNVs were known to exist but were assumed to be relatively rare and, as such, relatively unimportant (Freeman, et al., 2006). Recent estimates, however, place the percentage of the human genome that is subject to these variations at between ~12% (Hastings, Lupski, Rosenberg, & Ira, 2009) and an impressive ~30% (Zhang, et al., 2009), a significantly higher proportion than that of <1% in SNPs (Zhang, et al., 2009). Moreover, the rate of de novo CNVs is estimated to be between 100 and 10,000 times greater than that for SNPs depending on the region of the genome being examined (Fu, et al., 2010). Given that SNPs seem rare when compared to CNVs, perhaps due to the high likelihood of them causing deleterious coding errors (nonsense code, frameshift etc.) (Zhang, et al., 2009) and thus being eliminated by purifying selection, the mechanism behind the seemingly more ‘stable’ CNVs is of exceptional interest to those wishing to understand evolution at the genetic level.
One does, however, need to exercise a certain degree of caution in approaching CNVs as potentially positively selected mutations. The fact that, at the surface level, CNVs seem to be more abundant and stable should not be taken to mean that they are inherently more evolutionarily advantageous than SNPs, in fact many CNVs are thought to be neutral or somewhat deleterious (linked to disease states), it may just be that purifying selection acts with greater force on SNPs due to their capacity to disrupt normal gene expression at a more fundamental level, when compared to the inherent structural stability of a length of otherwise functional DNA that has simply been duplicated wholesale (Hastings, et al., 2009). Wholesale duplications (or deletions) of this kind have been argued to be the consequence of two related processes, homologous recombination (HR) and non-homologous recombination (NHR) (Hastings, et al., 2009).
HR and NHR are processes that act to repair double strand breakages in DNA through, aligning and reattaching lengths of DNA that ‘match’ those leading up to the breakage in the case of HR, or through attaching lengths of DNA that do not necessarily match in the case of NHR (Hastings, et al., 2009; Lieber, Ma, Pannicke, & Schwarz, 2003). In the case of HR, due to all human genomes containing regions of duplication called segmental duplications (SDs) (Lacroix, Oparina, & Mashkova, 2003) (these differ from CNVs in that these regions are generally not polymorphic), breakages in these areas can result in sequences from another section of any given chromosome, with near parity, being attached to this site, resulting in duplication (Hastings, et al., 2009) (Figure 1). This results in a net increase in copy number of any genes present. Alternatively, this same mechanism can result in a net loss (deletion) should intermediate genetic material be sheared when a near homologous strand from elsewhere in the genome, that lacks this intermediate material, is used to repair a break. As well as occurring in the repair of broken double stranded DNA, similar unequal exchanges can occur during unequal meiotic cross-over events as a function of HR, also potentially resulting in CNVs (Hastings, et al., 2009) (Figure 1). NHR functions similarly in that it rejoins broken double stranded DNA, with the exception that it does not require the same degree of homology between the two strands to be joined and can thus be considered a more efficient process despite the higher likelihood of error (Guirouilh-Barbat et al., 2004; Hastings, et al., 2009; Lieber, et al., 2003). This process is more common in mammals than HR (Guirouilh-Barbat, et al., 2004) and, as such, can be seen to be one of the main forces behind CNVs in the human genome.
Figure 1. How deletions and duplications can occur during unequal meiotic cross-over (a) and how deletions can occur as a result of repair by homologous recombination of broken double stranded DNA (b). Adapted from Hastings et al. (2009).
As mentioned, these changes in copy number are capable of producing phenotypic differences in individuals. These phenotypic impacts are principally produced through ‘dosage’ effects, or put simply, an increase or decrease in the volume of the gene product (structural protein, hormone, enzyme etc.) being produced as a consequence of changes in activity in the production or regulation of this product due to the duplication or deletion of related genes (Perry, 2008; Zhang, et al., 2009). It must be noted, however, that these effects are not linearly related to the copy number of the gene in question due to the fact that gene expression is a complex process that relies on regulatory sequences to influence the degree to which any given gene is expressed, if it is expressed at all. For example, CNV in the OPN1MW gene, associated with colour vision, is relatively common but it is only the copy nearest the intact regulatory sequence that is of consequence (Perry, 2008). Should an individual have a dysfunctional copy of this gene closest to the regulatory sequence, any additional copies of the functional gene elsewhere in the genome will not be expressed with the result that the individual will be colour-blind (Perry, 2008). This being said, there are numerous genes that are subject to CNVs that have known and observable dosage dependent effects, many of which will be discussed below.
Any genetic polymorphism that results in phenotypic characters that offer benefits or hindrances, in the survival stakes, to those carrying them can be said to influence evolutionary fitness. It stands to reason that should any given CNV be of advantage to fitness, it should increase in frequency among the population on whom it confers this advantage. Beginning with a comparison of the human genome to that of our closest extant relative, the chimpanzee (P. troglodytes), evidence shall be sought that CNVs have, indeed, played a crucial role in the divergence of these two species from a common ancestor some ~6 million years ago.
Copy Number Variation and the Divergent Evolution of Pan and Homo
Recent comparisons between the human and chimpanzee genomes have yielded a wealth of information about the respective evolutionary pasts of these two species. In a comparison of SDs present in the human and chimpanzee genomes, Cheng et al. (2005) have suggested that only 33% of these non-polymorphic duplications were not present in the chimpanzee genome, suggesting a high degree of similarity in terms of chromosomal geography when it comes to retained regions of duplication. This is of interest as it does suggest that the common ancestor of both of these species shared many of these SDs, and with regions of SD being ‘hotbeds’ for de novo CNV type mutations (SDs themselves are simply CNVs that have become relatively fixed) (Fu, et al., 2010; Mills, et al., 2011; Perry et al., 2008), this provides researchers with an understanding of where to focus when searching for CNVs.
Interpreting CNV similarities or differences between two species thought to have diverged so long ago, however, must be done with care. Perry et al. (2008) have convincingly argued that due to the relative instability of the regions that CNVs tend to inhabit and the rapid de novo mutation rate of CNVs, that any such observable similarities in CNVs (as opposed to the more consistent SDs) between these two genomes are likely the result of independent and relatively recent convergent evolutionary events rather than ancestral genomic traits maintained for ~6 million years. However, differences and similarities between patterns of genes enhanced or blocked through CNVs still can provide information about the differing evolutionary pressures experienced by these two species and offer insights into how, in terms of biological machinery, contemporary phenotypes were produced. Some of the CNVs of interest that have featured in recent work shall be discussed below.
In a study that utilised genomic comparisons across ten primate species, including humans and chimpanzees, Dumas et al. (2007) identified numerous CNVs in the human genome that seemed to correspond well with our palaeontolgoical understanding of hominin evolution. The increase in brain size and complexity in the hominin lineage, particularly within the last two million years, is a well accepted part of contemporary human evolutionary models (Navarrete, van Schaik, & Isler, 2011). In their study, Dumas et al. (2007) found a marked increase in the duplications of DNA containing the gene DUFF1220 when compared to other primate lineages. DUFF1220 is a gene thought to be related to higher cognitive processes based on the fact that damage to this gene results in mental retardation both in humans and experimental mice (Dumas, et al., 2007), suggesting that duplications of this gene in our evolutionary past may have contributed to the development of more sophisticated cognitive capabilities. Likewise, human specific duplications of NEK2 and ANAPC1 were also observed, these two genes being implicated in mitotic division and thought to be possible affecters of neocortex expansion in the hominin lineage (Dumas, et al., 2007). Furthermore, numerous models of human evolution have emphasised the role of endurance running in human specific traits such as sweating and fat metabolism, aspects of our evolutionary past that Dunbar et al. (2007) have argued may have been facilitated by copy number increases of AQP7. This gene is thought to be implicated in water and glycerol transport across cell membranes, and as such is of potential importance in both the evolution of more efficient extraction of energy from stored body fat and sweating as a response to overheating (Dumas, et al., 2007). It must be noted here, however, that the importance of ‘endurance’ or ‘persistence’ hypotheses of human evolution are not universally agreed upon, so other explanations for the increase in copy number of AQP7 may be possible.
In addition to the duplications identified by Dumas et al. (2007), a more recent genomic comparison between humans and chimpanzees by McLean et al. (2011) has identified 510 human lineage specific deletions. While many of these genetic losses fall within non-coding regions, numerous were associated with the deletion of regulatory sequences that are otherwise highly conserved among primates (McLean, et al., 2011). Two of these regulatory deletions were of particular interest, the first affecting expression of penile spines (associated with the androgen receptor gene) and the second relating to the expression of GADD45G, a tumor suppression gene, in parts of the brain thought to be related to the generation of cells responsible for neocortex expansion (McLean, et al., 2011). The absence of penile spines in humans can be argued to be related to changes in sexual behaviour in hominins, with one replier to McLean et al. (2011) suggesting that the reduction in sexual sensitivity this would cause could be associated with increased coital duration, generating greater bonding between the sexes in a lineage that was becoming increasingly monogamous (van Driel, 2011). As previously mentioned, the expansion of the brain in the human lineage is an area of importance, and the deletion of regulators that restrict brain size, in particular that of the neocortex, are of obvious significance when attempting to piece together the puzzle of brain size increase in the hominin line.
Taken together, it is clear that work within the last decade on comparing genetic duplications and deletions between the human and chimpanzee genomes has yielded significant insight into how observable phenotypic differences between these species have come to exist. While explanations of how these genetic changes came to be selected are likely to never be entirely agreed upon, it would appear that these changes do fit with several existing palaeontological hypotheses of how the Homo line evolved, particularly where brain expansion, endurance running and sexual behaviours are concerned.
Copy Number Variations in the Human Genome and Recent Human Evolution
Moving in focus from the divergence of our species from that of our nearest neighbour millions of years ago and the subsequent development of the hominin line, CNVs in the human genome can also tell us much about selective pressures in our recent evolutionary history. A particular application of this type of investigation is in considering how the adoption of agriculture and, consequently, higher density urban living following the Neolithic revolution ~10,000 years ago has produced selective pressures that have shaped the genomes of those populations involved (Richerson, Boyd, & Henrich, 2010). Here we shall focus on how dietary changes following the Neolithic revolution have generated a particularly well studied CNV and how the increased infectious disease burden of urban living has also generated a beneficial genetic duplication.
A particular characteristic of the diet of agricultural societies is their reliance on high starch grains such as wheat, millet, rice and barley (Diamond, 1991). Working from this fact, Perry et al. (2007) made an investigation of the correlation between CNVs in AMY1, the dose sensitive gene responsible for the production of salivary amylase, an enzyme utilised in the breakdown of starch, and dietary intake of starch across various populations including Europeans, Japanese, Hadza, Mbuti, Biaka, Datog and Yakut. It was found that the three populations with the greatest number of copies of the AMY1 gene were two agricultural societies, the Europeans and Japanese, and the Hadza, that relied less upon agriculture but had a high percentage of tubers and other starch rich foods in their diets (Novembre, Pritchard, & Coop, 2007; Perry, et al., 2007) (Figure 2). Interestingly, Mandel et al. (2010) have also found that increased copy numbers of AMY1 favourably affect the perception of the texture of starchy foods, increasing their desirability as a consistent part of the diet. These findings strongly suggest that relatively recent diet changes have produced sufficient selective pressures as to generate the accumulation of gene duplications that facilitate both the digestion and textural perception of important subsistence diet items.
Figure 2. The correlation between salivary amylase copy number and low or high starch diets in the study populations utilised in Perry et al. (2007). Novembre et al. (2007).
The development of higher density living arrangements (towns and eventually cities) as a consequence of increasingly efficient agricultural practices, in parts of the world such as the Fertile Crescent, North Africa, Europe, India and East Asia, brought with it an increase in the infectious disease burden (Diamond, 1991). Based on recent evidence to be discussed here, this can be argued to have generated sufficient selective pressure as to favour those individuals with CNVs that offered some resistance to these diseases. Recent research by Hardwick et al. (2011) into the geographic distribution copy numbers of a high expressing version of a gene associated with the antimicrobial properties of epithelial tissue (beta-defensin, DEFB103), found that high copy numbers of this gene were concentrated in East Asian populations. Given the historically high burden of influenza and other zoonotic viral infections of the epithelium in this area, in addition to the relatively long history of high density population centres, high copy numbers of this gene were argued to have accumulated as a consequence of their conferral of greater resistance to these infections (Hardwick, et al., 2011). Given other recent research into a non-CNV type polymorphism, thought to confer greater resistance to tuberculosis (Barnes, Duda, Pybus, & Thomas, 2011), that has shown a strong frequency correlation with populations with a long history of urban living, the explanation offered by Hardwick et al. (2011) of the high copy numbers of the high expressing DEFB103 variant, seen in East Asia, seem quite plausible.
While only two CNVs have been offered here as having strong correlations with relatively recent human lifestyle changes, namely niche construction in the form of agriculture and urbanisation, weight can be added to these examples by referring to the more abundant data on SNPs thought to be associated with post-Neolithic revolution changes in selective pressures. Studies by Wang et al. (2006) and Hawks et al. (2007) have identified hundreds of genes on which, based on linkage disequilibrium, strong selection seems to have been operating within the last ~40,000 years, with Hawks et al. (2007) suggesting that many of these are likely to have occurred within the last ~10,000 years as a consequence of post-Neolithic revolution lifestyle changes and population expansions. Based on this, it seems highly probable that many more CNVs relating to adaptations to a ‘modernising world’ are likely to be identified in the human genome of those populations impacted by these changes.
Conclusion
In summary, the inter and intra species study of copy number variations in the human genome can tell us much about the genetic machinery that underlies the observable phenotypic differences between modern humans and our nearest extant relative the chimpanzee, as well as those between modern human geographical populations. Additionally, evidence of positive selection for certain gene configurations, be they duplications or deletions, in the past can offer some insight into the selective pressures experienced by ancestral hominin populations. While it is estimated here that future studies are likely to identify further examples of CNVs useful for the purposes of understanding human evolution, both recently and in the distant past, such data must always be interpreted carefully due to the fact that the de novo mutation rate of CNVs is relatively high, reducing the likelihood that any observably frequent copy number variant is indeed ancestral. Additionally, while this essay has largely omitted the technical details of how CNVs are identified in the human genome, the focus of much contemporary research on the identification of SNPs does relatively little to aid the advancement of techniques useful for more efficient CNV identification. Should the study of CNVs gain anything like the momentum experienced in the study of SNPs, it is predicted here that the subsequent advances in detection techniques should yield a marked increase in the discovery of the kinds of CNVs described here, greatly enhancing our understanding of how this particular genetic mutation process has contributed to human evolution.
References
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Chen, W., Hayward, C., Wright, A. F., Hicks, A. A., Vitart, V., Knott, S., et al. (2011). Copy Number Variation across European Populations. PLoS ONE, 6(8), e23087.
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Lee, J. A., & Lupski, J. R. (2006). Genomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders. Neuron, 52, 103-121.
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In a previous post, I briefly discussed the notion of a speciation reversal and how this could be seen to have applied to the rejoining of the phylogenetic branches of Homo neanderthalensis and Homo sapiens some time between 50 and 25 thousand years ago (not a discrete event of course, don’t bite into that particular serpent’s apple, it would have occurred gradually). In an update at the end of that post, I mentioned a paper that seemed to support a similar point of view to some degree. The paper is cited below:
Barton, C. M., & Riel-Salvatore, J. (2012). Agents of Change: Modeling Biocultural Evolution in Upper Pleistocene Western Eurasia. Advances in Complex Systems, 15(1-2).
Utilising some interesting computer models, Barton & Riel-Salvatore have argued that rather than being overwhelmed and ultimately destroyed by their technologically/culturally superior cousins, Neanderthals may well have disappeared as a result of something slightly less intuitive. It was argued that it was the roughly equivalent level of cultural sophistication in Neanderthals that spelled their doom as a distinct species. I saw the double take you just did, let me explain. If the Neanderthals were in possession of a highly adaptable culture that ultimately provided adaptive solutions to the fluctuating climate of the middle-late Pleistocene AND were biologically capable of mating with anatomically modern humans (AMH), would not their adaptive behaviour have eventually pushed them into increasing contact with the equally culturally adaptable new arrivals, resulting in cultural exchange and eventually hybridisation to the point of non-existence of the smaller population? Kazaam! Speciation reversal!
This idea is offered further weight by a paper published in Molecular Biology & Evolution in late February, see below:
Dalen, L., Orlando, L., Shapiro, B., Durling, M. B. m., Quam, R., Gilbert, M. T. P., et al. (2012). Partial genetic turnover in neandertals: continuity in the east and population replacement in the west. Molecular Biology and Evolution.
Essentially, based on molecular evidence, Dalen and friends argue that prior to exposure to AMH, Neanderthal populations were likely to have been in decline already, having lost a large proportion of their numbers (and genetic diversity) to aforementioned Pleistocene climate instabilities. The simple truth is, no matter how culturally clever your species, an ice-age poses incredible ecological challenges that are likely to dwindle the numbers of any animal attempting to weather it. This saw the smaller remaining Neanderthal populations migrating southward toward more habitable lands, right into the path of AMH, expanding north from their much more hospitable sub-tropical birthplace. If Neanderthal numbers were low enough, this may have made mating with the biologically compatible and more plentiful AMH the only viable survival strategy. There is even a certain logic to arguing that this may have been both culturally and biologically advantageous to AMH. Ultimately, the smaller contributor to any given enduring admixture will eventually be consumed, resulting in a more homogenous population overall (the new hybrid species).
While I have no doubts that some conflict was likely between groups of AMH and Neanderthals, given the above I would be more inclined to say that their meetings were more cordial than that. I would love to hear what any readers might think of this, especially those of you with a finger in the paleontological pie.
- confusedious
It seems YT is hitting a new low. A post by thunderfoot, a well known atheist v-blogger, has stated that he has been asked to remove his videos as they have been flagged as ‘religiously offensive’. I sincerely hope that this decision swings both ways, as most religions seem to be offended by other religions in general they should, by this logic, ban all videos of a religious nature. Fat chance of that however, most likely YT will become a one sided theological mudslide.
I call on anyone who reads this post to immediately cease use of YT henceforth until they deliver on a policy of equality and freedom of speech.
Let’s hope this turns out to be a mere speed bump rather than a wall.
UPDATE: It would appear that YT has put the videos that were pulled down back online due to a huge public response. Let’s hope that they don’t try this crap again. Should they attempt any such action in the future I believe it should be equally spread or met with boycott.
A recent paper in Nature described how the collapse of an ecological niche, containing a species closely related to those in adjoining niches, could result in an interesting kind of double extinction (the term is used loosely here) as a consequence of both populations merging in the still viable eco-niche, interbreeding and producing a new hybrid species. While this particular paper spoke of varieties of lake fish, the situation with the discovery of Neanderthal genes in the modern human genome immediately jumped to mind.
For anyone interested, the paper I speak of is:
‘Eutrophication causes speciation reversal in whitefish adaptive radiations’ by Vonlanthen et al. in Nature volume 482, pages 357-363.
While there are many schools of thought on how this interbreeding took place, a common viewpoint is that Homos neanderthalensis and sapiens simply represented different radiations, and that the later (sapiens) simply displaced/absorbed the earlier (neanderthalensis) through either direct or indirect competition. The hybridisation of these species seems to have been treated by many workers as something that ‘just happened’ and really deserves greater thought. Could it be that climactic changes pressed Neanderthal populations into an overlap with their expansive ‘modern’ relatives? Who says that sapiens was the only population on the move? Additionally, if climate change had the result of reducing Neanderthal numbers then a shortage of mates may well have compounded this situaiton, drawing neanderthal populations closer to modern groups of out necessity. This could have fostered a situation of speciation reversal as described by Vonlanthen et al. with their lake fish. Worth thinking about, the person typing this article is, after all, a member of the resultant hybrid species.
Update: It seems that a recent paper has pressed the same viewpoint I was getting at above. I shall post on this shortly.
As a person making a full time occupation of studying and researching aspects of human evolution, I find myself spending a rather surprising amount of time defending my viewpoints to blinkered religious nutballs. In saying this, it’s fairly evident that I am an atheist and a happy one at that. In a previous post I spoke a little about how I find meaning in science and I may explore that a little more later in another post (thank you to those who sent encouraging emails regarding this).
Anyhow, in my YouTube procrastinations I have stumbled across two terrific video bloggers dedicated to fighting for atheism and rationalist viewpoints. Much like these two, I’m no longer comfortable with allowing religious types to be involved with the media or politics and intend to take a more active stance in opposing those who would push their whacky convictions on others.
First up, we have AronRa, a Texan who has been a vocal opponent of the teaching of creationism in schools. Despite his terrifying visage, the man is exceptionally eloquent and one of the best arguers of rationalism I have ever come across.
Find him here: http://www.youtube.com/user/aronra?ob=
Secondly, we have Thunderf00t, the maker of a terrific series exploring why it is that we laugh at creationists, among other brilliant vids. His videos are highly entertaining and from personal experience I can tell you that showing them to religious types is sure to make them blush if not storm off and never talk to you ever again (either way, good result).
Find him here: http://www.youtube.com/user/Thunderf00t
I hope you enjoy these! Should I have time, I’m considering a vlog of my own, though first I shall focus on getting more articles up on this blog! The cobwebs are growing thick and fast!
Recent, Rapid Human Evolution: Is Gene-Culture Coevolution Responsible?
Introduction
The notion that human cultural innovation, and the consequential capacity to change the world around us, has allowed us to sufficiently divorce ourselves from the natural world as to escape natural selection, is pervasive. So much so that entire bodies of human sociobiological work have been built upon it, prime among these being the field of evolutionary psychology with its assumptions that our Neolithic minds have been unable to keep up with our rapidly changing, culturally constructed world (Laland & Brown, 2011). Recent work in molecular evolutionary biology has begun to seriously degrade the plausibility of such viewpoints. Utilising a survey of the human genome, Hawks et al. (2007) have argued, based on single nucleotide polymorphisms and linkage disequilibrium, that in response to human cultural innovations that have occurred within the last 10,000 years, human biological evolution has, far from conforming with the common view above, experienced a period of unprecedented acceleration. It would appear that rather than reducing selection pressures, our cultural innovations (namely agriculture and urbanisation), mobilised as a kind of niche construction (Laland, 2008), have generated potent selective pressures of their own.
The field of ‘gene-culture coevolution’ stands in an ideal location to offer explanations on how these man-made environmental alterations have in turn altered our genes at an unprecedented rate. While much of the early work in this field was theoretical/mathematical in nature (Feldman & Cavalli-Sforza, 1976; Laland & Brown, 2011), the mapping of the human genome and our increasing understanding of which genes are related to particular phenotypes has allowed workers in this field to assess with ever increasing accuracy which genes are likely to have been under recent, culturally mediated, selective pressure (Richerson, Boyd, & Henrich, 2010).
Wang et al. (2006), utilising molecular techniques, identified several functional groupings of genes that seem to have undergone strong recent selection. Among these groupings, three are of particular interest when viewed from the perspective of gene-culture coevolution: genes relating to food processing, genes involved in disease resistance and genes expressed in the brain. This essay shall evaluate a selection of alleles that fall within these three categories in an effort to assess the likelihood that cultural innovations in the last 10,000 years have influenced their selection. In following with the views of Diamond (1991), the position that agriculture, as a niche construction activity, is the key to the development of complex societies shall be taken. Genes that seem to have been placed under greater selective pressure by the adoption of this cultural innovation and associated dietary changes shall be explored first. Secondly, based upon the idea that an agricultural base allows populations of greater density to be built (Diamond, 1991), evidence of genetic change related to resistance of diseases endemic to highly populated areas shall be examined. Finally, evidence for recent selection of genes associated with brain function, the ultimate human tool for social interaction, shall be considered in the light of social changes generated by agriculture and increases in population density.
Agriculture, Diet and Genes
In considering the last 10,000 years, one human cultural innovation dwarfs all others for its flow on effects in terms of the human environment, agriculture (Diamond, 1991). Agriculture is thought to have arisen independently in (and then culturally radiated out from) various regions, including the Fertile Crescent, Central and Northern Africa, East Asia and the Americas between 7,000 and 10,000 years ago (Diamond, 1991). It is conceivable that this ‘Neolithic Revolution’ marked the beginning of the evolutionary acceleration identified by Hawks et al. (2007). In generating a stable niche in terms of food availability, perhaps in response to a stabilising climate (Richerson, Boyd, & Bettinger, 2001), Neolithic humans likely found themselves consuming a much more homogenous diet and/or utilising nutrient sources previously less favoured (Richerson, et al., 2010). As shall be demonstrated, the resultant change in diet was adequate to increase selection for certain genes that allowed these early agriculturalists to make the most of the nutrient sources present.
The domestication of rice, barley, wheat and other cereal crops, along with root vegetables like potatoes and yams, significantly increased the intake of starch for Neolithic farmers (Meisenberg, 2008). This would have generated a positive selective pressure for genes allowing more efficient processing of this particular plant carbohydrate. Evidence of this is seen today, as the copy number of the gene AMY1, responsible for the production of salivary amylase (an enzyme that breaks starch into simpler sugars), seems to vary by population group in relation to their history of starch consumption (Ley, Lozupone, Hamady, Knight, & Gordon, 2008; Richerson, et al., 2010). Essentially, populations with a long history of agriculture and thus a starchy diet, have more copies of this particular gene. It is highly likely that this trend had its origins in the Neolithic agricultural revolution.
Molecular evidence derived from the DNA of Southern Chinese populations seems to indicate that fermentation of domesticated plants (the production of alcohol) followed soon after the advent of rice based agriculture in this region (Peng et al., 2010). This trend seems to be temporally true of other early agricultural centers also with various ancient populations (Egypt, Mesopotamia, Greece) seeming to have a long history of alcohol production, based on archaeological evidence (Dietler, 2006). The negative health affects of excessive alcohol consumption are well known today and it would seem that these produced selective pressure for genes that enhance the breakdown of this chemical (Peng, et al., 2010). In the case of the Chinese population mentioned, the enrichment of a certain class of alcohol dehydrogenase sequence polymorphism, dated to approximately 7,000-10,000 years ago, supports this notion (Peng, et al., 2010). Should alcohol consumption indeed generate selective pressures like those posed here, it is expected that other populations with a long history of alcohol consumption should show similar recent adaptations as a function of convergent evolution.
Agriculture, of course, encompasses more than the domestication of plants. The domestication of animals is also thought to have generated pressure for genetic change in early farmers (Laland, Odling-Smee, & Myles, 2010). Perhaps the most well studied example of this relates to the consumption of milk and the persistence of lactase production in adults in populations with a history of this practice (Laland, et al., 2010; Richerson, et al., 2010). The presence of the gene responsible for the persistence of lactase production in European adults (the word persistence is used as all humans produce lactase as infants and generally cease production sometime after weaning in non-milk consuming populations) is estimated to have reached significant frequencies some 5,000-10,000 years ago, based on molecular evidence, and is absent in DNA extracted from ancient remains from earlier time periods (Laland, et al., 2010). This matches relatively closely with our archaeological understanding of when animal domestication became widespread (Diamond, 1991). The genetic mechanisms behind lactase persistence in non-European populations present compelling evidence for the selective strength of this cultural innovation as different, independently selected, genes are responsible in some populations (Enattah et al., 2008).
In addition to the diet related adaptations mentioned above, agriculture enabled significant changes in human demography. With a stable, agriculture based, source of resources, populations became more sedentary and greater numbers of individuals were able to be supported by a given tract of land (Diamond, 1991). Hawks et al. (2007) have argued that this population boom was in fact responsible for the genetic diversity necessary to fuel the rapid digestive adaptations mentioned and as shall be demonstrated, was likely a crucial factor in the genetic adaptations relating to disease resistance and brain function to be expounded below.
Population Growth, Disease Burden and Genes of Resistance
The Neolithic agricultural revolution allowed humans to live at densities that had been impossible prior (Diamond, 1991), in turn, this generated an environment in which infectious diseases were readily transmissible (Barnes, Duda, Pybus, & Thomas, 2011). It is conceivable that following outbreaks of diseases endemic to populated areas, individuals with a biological edge, alleles of resistance, would be more likely to pass these useful genes onto future generations. Several recent research projects seem to support this line of reasoning.
One of the most often discussed examples of recent human evolution relating to disease resistance is the advent, and subsequent increase in frequency, of the sickle cell (HbS) gene in response to high rates of infection with malaria in West Africa (Richerson, et al., 2010). In this case, it is thought that the cultivation of yams by West Africans generated large areas of standing water that had previously been non-existent in the area, allowing malaria harbouring mosquitos to proliferate (Laland, 2008). This combined with what was likely a growing agricultural population, created sufficient selective pressure that the HbS gene, only beneficial in a heterozygous state (Laland, 2008), was able to reach incredibly high frequencies for an otherwise fitness reducing, even lethal, gene (Mansilla-Soto, Rivière, & Sadelain, 2011). This speaks volumes for the selective pressures that must have been present, as nothing but an incredibly strong selective environment would encourage the presence of a gene that is only beneficial to 50% of offspring (see Appendix 1).
Tuberculosis is another disease with a long history in human populations, with remains containing molecular traces of this infection being identified from as long ago as 3,000 BCE in Egypt (Zink et al., 2003). It is highly likely that the disease is much older than this, though the debate surrounding its history as a human pathogen is still underway (Smith, Hewinson, Kremer, Brosch, & Gordon, 2009). Recent work on SLC11A1 1729 + 55del4, an allele associated with tuberculosis resistance, has uncovered a positive correlation between the frequency of this gene and the length of urban history for a given population (Barnes, et al., 2011) (Figure 1). This is strong evidence for the above assertion that increased population density should increase disease load and thus select for individuals with resistance to problem infectious diseases.
Figure 1. Time since first urban settlement is displayed on the x-axis while frequency of the allele for tuberculosis resistance is displayed on the y-axis. Mathematical lines of best fit are as published in Barnes et al. (2011). Adapted from Barnes et al. (2011).
It is highly likely that selective pressure from other known population diseases has played a similar role in recent human evolution. Wang et al. (2006) identified at least a half-dozen genes relating to host-pathogen interaction in addition to those given above, some of which with functions that are not yet adequately understood. It is reasonable to predict that should future research into genes associated with resistance to other infectious diseases historically endemic to areas of high population, be carried out (see Conclusion for suggestions), further evidence of how cultural lifestyle changes can influence human biological evolution will be found.
Cultural Change and the Human Brain: How Sociality Shapes Our Genes
Ultimately, living in social groups, especially those of the size and complexity characteristic of large agricultural settlements (and eventually cities), relied upon the ability of ancient humans to successfully interact with one another. If cultural innovations, such as agriculture and following this settlements and cities, have produced selective pressures sufficient to change our genes with regard to food digestion and disease resistance, it is sensible to infer that changes to genes relating to our neurophysiology, and thus interactive capacities, should also be present. The findings of Wang et al. (2006) and Laland (2008), among others, seem to suggest just this.
While the brain expressed genes identified by Wang et al. (2006) are thought to have undergone rapid, recent selection, their functions are unfortunately as of yet unknown. Laland (2008), however, lists 29 recently selected genes thought to be related to nervous system and brain ontogeny, brain function and, importantly, language skills and learning. The role of learning and communication in cultural innovation is extremely important (Laland & Hoppitt, 2003), it is thus unsurprising that genes relating to such functions have undergone recent selection in light of the societal changes discussed prior.
Perhaps more interestingly, work within the last two years has identified potentially recent polymorphisms of a gene that may represent a genetic consequence of selective pressures generated by a cultural interaction style. Chiao & Blizinsky (2009) reported that the 5-HTTLPR gene, associated with serotonin reuptake and thus mood, is present in long and short alleles that are geographically distributed in a manner fairly consistent with our notions of collectivist and individualist cultures (Figure 2). The short allele, argued to be related to collectivist cultures (Chiao & Blizinsky, 2009), essentially allows less reuptake of serotonin at the synapses, much the same affect exerted by many of today’s common antidepressant and antianxiety drugs (Bullock, Manias, & Galbraith, 2006). This has the mean result of elevating mood and, as Chiao & Blizinksy (2009) argue, reducing rates of behaviour that are harmful to social harmony (and thus fitness reducing, for both the errant individual and the group).
Furthermore, Chiao & Blizinksy (2009), relating back to the previous section on infectious disease, propose that collectivism seems to correlate with populations with a history of high disease burden and argue that selection for collectivist behaviour is somehow protective in this regard. This remains to be explored more comprehensively and may well represent a case of correlation as opposed to causation. While the question of how societies come to be collectivist or individualist to begin with remains largely unanswered, this study does provide a relatively robust example of a relationship that exists between a gene and an observable cultural selective pressure. It is conceivable that such pressures have exerted impacts on other genes relating to behaviour or cognition. Genes relating to other neurotransmitters, perhaps dopamine or gamma-amino butyric acid, seem likely targets given their role in the regulation of human emotional states.
Figure 2. Distribution of the S (short) allele of the 5-HTTLPR gene in relation to individualism-collectivism and prevalence of anxiety across countries. Adapted from Chiao & Blizinsky (2009).
Conclusion
Utilising modern molecular techniques, it is evident that a considerable number of human genes have undergone recent and rapid change (Hawks, et al., 2007). Many of these changes are estimated to have occurred within the last 10,000 years (Hawks, et al., 2007), a period of great cultural change that saw the adoption of agriculture and as a consequence sedentary settlements that, in some cases, grew to become the first urban centres (Diamond, 1991). Generally, niche construction activities are undertaken by animals in order to reduce the impact of environmental change, and this was likely the case for the first Neolithic farmers (Laland, 2008; Richerson, et al., 2001). The flow on effects of agriculture and subsequent human cultural innovation, however, produced a novel and rapidly changing environment with selective pressures of its own. It could be argued that these culturally mediated selective pressures outstripped their ecological predecessors for selective sway, generating a range of genetic adaptations related to diet, resistance to disease and neurophysiology (Barnes, et al., 2011; Chiao & Blizinsky, 2009; Laland, 2008; Richerson, et al., 2010), at a rate possibly unmatched in prior Homo evolution.
As further studies of the human genome for signatures of recent evolutionary change are performed, it is anticipated that further evidence for this period of rapid evolution will be found in gene-culture coevolutionary studies. Of particular interest to future researchers might be genes associated with resistance to dietary diseases (diabetes, obesity and vitamin D deficiency), other diseases endemic to highly populated areas (smallpox, the black death, influenza and more recently, HIV/AIDS) and the search for further evidence of cognitive changes related to an increasingly social lifestyle, especially where tolerance of non-kin is concerned.
In closing, it should be mentioned here that the above model, for the sake of brevity, has not considered how a lack of agricultural culture would manifest in the genetics of hunter-gatherer societies. It is predicted that, far from refuting the above, populations with limited exposure to agriculture, and as a consequence sedentary settlements of high population density, should display recent reactive selection only in accordance with the magnitude of their exposure. Should this hypothesis hold, it would be both complementary to, and supportive of, the main argument here given.
References
Barnes, I., Duda, A., Pybus, O. G., & Thomas, M. G. (2011). ANCIENT URBANIZATION PREDICTS GENETIC RESISTANCE TO TUBERCULOSIS. Evolution, 65(3), 842-848.
Bullock, S., Manias, E., & Galbraith, A. (2006). Fundamentals of Pharmacology. Frenchs Forest: Pearson Australia.
Chiao, J. Y., & Blizinsky, K. D. (2009). Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene. Proceedings of The Royal Society: Biological Sciences, 277, 529-537.
Diamond, J. (1991). Guns, Germs and Steel. London: Jonathan Cape.
Dietler, M. (2006). Alcohol: Anthropological/Archaeological Perspectives. Annual Review of Anthropology, 35, 229-249.
Enattah, N. S., Jensen, T. G. K., Nielsen, M., Lewinski, R., Kuokkanen, M., Rasinpera, H., et al. (2008). Independent Introduction of Two Lactase-Persistence Alleles into Human Populations Reflects Different History of Adaptation to Milk Culture. The American Journal of Human Genetics, 82, 57-72.
Feldman, M. W., & Cavalli-Sforza, L. L. (1976). Cultural and biological evolutionary processes, selection for a trait under complex transmission. Theoretical Population Biology, 9, 238-259.
Hawks, J., Wang, E. T., Cochran, G. M., Harpending, H. C., & Moyzis, R. K. (2007). Recent acceleration of human adaptive evolution. Proceedings of the National Academy of Sciences, 104(52), 20753-20758.
Laland, K. N. (2008). Exploring gene-cultural interactions: insights from handedness, sexual selection and niche-construction case studies. Philosophical Transactions of The Royal Society: Biological Sciences, 363, 3577-3589.
Laland, K. N., & Brown, G. R. (2011). Sense & Nonsense (2nd ed.). Oxford: Oxford.
Laland, K. N., & Hoppitt, W. (2003). Do animals have culture? Evolutionary Anthropology: Issues, News, and Reviews, 12(3), 150-159.
Laland, K. N., Odling-Smee, J., & Myles, S. (2010). How culture shaped the human genome: bring genetics and the human sciences together. Nature Reviews: Genetics, 11, 137-148.
Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R., & Gordon, J. I. (2008). Worlds within worlds: evolution of the vertebrate gut microbiota. [10.1038/nrmicro1978]. Nat Rev Micro, 6(10), 776-788.
Mansilla-Soto, J., Rivière, I., & Sadelain, M. (2011). Genetic strategies for the treatment of sickle cell anaemia. British Journal of Haematology, 154(6), 715-727.
Meisenberg, G. (2008). On the Time Scale of Human Evolution: Evidence for Recent Adaptive Evolution. Mankind Quarterly, 48(4), 407-444.
Peng, Y., Shi, H., Qi, X., Xiao, C., Zhong, H., Ma, R. Z., et al. (2010). The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history. BMC Evolutionary Biology, 10(15), 1-8.
Richerson, P. J., Boyd, R., & Bettinger, R. L. (2001). Was Agriculture Impossible During the Pleistocene but Mandatory During the Holocene? A Climate Change Hypothesis. American Antiquity, 66(3), 387-411.
Richerson, P. J., Boyd, R., & Henrich, J. (2010). Gene-culture coevolution in the age of genomics. Proceedings of the National Academy of Sciences, 107(Supplement 2), 8985-8992.
Smith, N., Hewinson, R., Kremer, K., Brosch, R., & Gordon, S. (2009). Myths and misconceptions: the origin and evolution of Mycobacterium tuberculosis. Microbiology, 7, 537-544.
Wang, E. T., Kodama, G., Baldi, P., & Moyzis, R. K. (2006). Global landscape of recent inferred Darwinian selection for Homo sapiens. Proceedings of the National Academy of Sciences of the United States of America, 103(1), 135-140.
Zink, A. R., Sola, C., Reichl, U., Grabner, W., Rastogi, N., Wolf, H., et al. (2003). Characterizatio of Mycobacterium tuberculosis Complex DNAs from Egyptian Mummies by Spoligotyping. Journal of Clinical Microbiology, 41(1), 359-367.
Appendix 1.
A cross between two parents heterozygous for the HbS gene will result, statistically in: 25% homozygous HbS (potentially lethal), 50% heterozygous HbS (protection against malaria) and 25% homozygous non-HbS (no malaria protection, under high disease burden potentially deadly). Similarly, a cross between a non-HbS homozygote and a heterozygote will produce 50% heterozygote offspring but with the other 50% being non-HbS homozygotes. A cross involving a HbS homozygote is less likely due to the deleterious nature of this genotype.
