Tag: Genetics

Visualizing genetic variation

By Razib Khan | February 12, 2013 5:31 am

I’ve been thinking about how best to visualize PCA/MDS type of results, which allow for the two dimensional representation of genetic variation. Below are a few of my efforts with a data set I have. You can see the individuals in gray, but also ellipses which cover ~95% of the distribution of a given population.

Please click the images for a larger version. They represent coordinate 1 on the y axis and 2 on the z axis derive from a multidimesional scaling representing identity by state across individuals.

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CATEGORIZED UNDER: Genomics, Geography
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Social barriers to Indian public health & non-Aryan “invasions”

By Razib Khan | February 5, 2013 1:16 pm

A reader points me to a talk given by David Reich at the Center for Human Genetic Research 2013 Retreat. One of the issues Reich brought up is old, but perhaps worth reemphasizing: due to endogamy many South Asians carry a higher load of recessive ailments. This is not due to recent inbreeding (which is barred by custom in many South Asian groups, which enforce kin-level exogamy), but long term genetic isolation. Over time even a moderate sized population can be affected by drift. This was one of the major points in the 2009 paper Reconstructing Indian History, but not one particularly emphasized in the press follow up. A major implication is that a relatively simple public health measure for South Asians would be to marry outside of their jati. The social or genetic distance need not be great. But one generation of outbreeding should “mask” many of the deleterious alleles. If this model is correct one should be able to track decreases in morbidity within the American South Asian population, where there are many inter-caste and inter-regional marriages (yes, this is between people of putative high status, but this doesn’t matter).

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Phylogenetics implies Austro-Asiatic are intrusive to India

By Razib Khan | January 29, 2013 6:58 am

Most people in South Asia speak one of two varieties of language, Indo-Aryan and Dravidian. These two are not particularly closely related. Indo-Aryan is an Indo-European language, as is evident in the plethora of obvious cognates with other Indo-European dialects. I have a minimal fluency in Bengali, the easternmost of the Indo-European languages, and quite a bit more fluency with English, one of the most westernmost, and it was evident to me rather early on (e.g., grass vs. gash, man vs. manush, nose vs. nak). In contrast to me Dravidian languages are peculiar because the accent and cadence are clearly South Asian, but they are utterly impenetrable (though there are many loan words into Indo-Aryan from Dravidian).

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Neurodiversity and genetic diversity

By Razib Khan | January 24, 2013 4:17 am

In the links below I alluded to a controversy over the “Neurodiversity movement”. The basic issue is that people with Asperger syndrome and high functioning autism are being accused of putting their concerns above and beyond those of the large number of mentally disabled autistic individuals (some of whom are non-verbal, and exhibit severe cognitive deficits) in the grab for “rights.” Rights here understood as the rights which black Americans, women, and gays have claimed, to be recognized as equal before the law and endowed with the same value in the eyes of society. As a deep philosophical matter I’m skeptical of Rights in a fundamental sense. As a conservative I’m skeptical of the push for a huge array of rights by a plethora identity groups. Socially recognized rights are valuable, and are cheapened and debased by dispensing them too liberally.

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Why the future won’t be genetically homogeneous

By Razib Khan | January 5, 2013 10:52 pm

While reading The Founders of Evolutionary Genetics I encountered a chapter where the late James F. Crow admitted that he had a new insight every time he reread R. A. Fisher’s The Genetical Theory of Natural Selection. This prompted me to put down The Founders of Evolutionary Genetics after finishing Crow’s chapter and pick up my copy of The Genetical Theory of Natural Selection. I’ve read it before, but this is as good a time as any to give it another crack.

Almost immediately Fisher aims at one of the major conundrums of 19th century theory of Darwinian evolution: how was variation maintained? The logic and conclusions strike you like a hammer. Charles Darwin and most of his contemporaries held to a blending model of inheritance, where offspring reflect a synthesis of their parental values. As it happens this aligns well with human intuition. Across their traits offspring are a synthesis of their parents. But blending presents a major problem for Darwin’s theory of adaptation via natural selection, because it erodes the variation which is the raw material upon which selection must act. It is a famously peculiar fact that the abstraction of the gene was formulated over 50 years before the concrete physical embodiment of the gene, DNA, was ascertained with any confidence. In the first chapter of The Genetical Theory R. A. Fisher suggests that the logical reality of persistent copious heritable variation all around us should have forced scholars to the inference that inheritance proceeded via particulate and discrete means, as these processes do not diminish variation indefinitely in the manner which is entailed by blending.

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We are Nature

By Razib Khan | December 13, 2012 10:03 am

There’s an interesting piece in Slate, The Great Schism in the Environmental Movement, which seems to be a distillation of trends which have been bubbling within the modern environmentalist movement for a generation now (I’ve read earlier manifestos in a similar vein). I can’t assess the magnitude of the shift, but here’s the top-line:

But that is a false construct that scientists and scholars have been demolishing the past few decades. Besides, there’s a growing scientific consensus that the contemporary human footprint—our cities, suburban sprawl, dams, agriculture, greenhouse gases, etc.—has so massively transformed the planet as to usher in a new geological epoch. It’s called the Anthropocene.

Modernist greens don’t dispute the ecological tumult associated with the Anthropocene. But this is the world as it is, they say, so we might as well reconcile the needs of people with the needs of nature. To this end, Kareiva advises conservationists to craft “a new vision of a planet in which nature—forests, wetlands, diverse species, and other ancient ecosystems—exists amid a wide variety of modern, human landscapes.”

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A lighter shade of brown: Dan MacArthur, look east or south!

By Razib Khan | December 12, 2012 4:58 pm

South Indian Udupi cuisine

In the post below I offered up my supposition that Dan MacArthur’s ancestry is unlikely to be Northwest Indian, which precludes a Romani origin for his South Asian ancestry. Indeed this is almost certainly so, Dienekes Pontikos followed up my crude analyses with IBD-sharing calculations (IBD = ‘identity by descent,’ which is basically what you would think it is). The South Asian population which MacArthur has the closest affinity to is from Karnataka, which is one of the Dravidian speaking states of the South. This does not necessarily refute my earlier contention, as aside from Brahmins most Bengalis seem to have broad South Indian affinities, except for the fact that they often have more East Asian ancestry.

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MORE ABOUT: Genetics, Genomics

We don’t know why Ethiopians breathe easy

By Razib Khan | December 11, 2012 11:40 pm

Most people are aware that altitude imposes constraints on individual performance and function. Much of this is flexible; athletes who train at high altitudes may gain a performance edge. But over the long term there are costs, just as there are with computers which are ‘overclocked.’ This is the point where you make the transition from physiology to evolution. Residence at high altitude entails strong selective pressures on populations. Over the past few years there has been a great deal of exploration of the genetics of long resident high altitude groups, the Tibetans, Peruvians, and Ethiopians.

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The origins of the Romani determined definitively

By Razib Khan | December 9, 2012 1:52 pm

In many cases there are questions of a historical and ethnographic nature which are subject to controversy and debate. Scholarly arguments are laid out, and further dispute ensues. For decades progress seems fleeting, as one hypothesis is accepted, only to be subject to later revision. This sort of pattern gives succor to the most cynical and jaded of ‘Post Modern’ set, especially when the ‘discourse’ in question is in the domain of science.

But thankfully these debates can come to an end in some cases. So it is with the origins of the European Romani, better known as ‘Gypsies’ (though the Roma are the most well known of the Romani, other groups within Europe have different ethnonyms). Obviously many of the basic elements have long been there, but I think the most recent genetic work now establishes a level of closure. Taking a step back, what do we know?

1) The Romani language seems to be Indo-Aryan, with a likely affinity with the northwest group of Indo-Aryan languages

2) The Romani presence in Europe only dates to the past ~1,000 years, with an entry point in the Byzantine Empire

3) They are an admixture between an ancestral Indian element, and local populations

4) Their history of endogamy has resulted in a strong genetic drift effect

The two papers which seem to nail the coffin shut on these questions use somewhat different methodologies. One relies on Y chromosomal STRs (hypervariable repeat regions) to generate a paternal phylogeny. Focusing just on the paternal phylogeny allows for one to make very robust genealogical inferences. Additionally, the authors had a very large data set across India. Their goal was to ascertain the exact region of origin of the Romani before they left India. As noted in bullet #1 there is already some evidence from their language that this must be in northwest India. The second paper uses a SNP-chip; hundreds of thousands of autosomal markers. This has been done to death for other populations, so the method isn’t new. Rather, it is that it is now being applied to the Romani.

First, the Y chromosomal paper. The Phylogeography of Y-Chromosome Haplogroup H1a1a-M82 Reveals the Likely Indian Origin of the European Romani Populations:

Linguistic and genetic studies on Roma populations inhabited in Europe have unequivocally traced these populations to the Indian subcontinent. However, the exact parental population group and time of the out-of-India dispersal have remained disputed. In the absence of archaeological records and with only scanty historical documentation of the Roma, comparative linguistic studies were the first to identify their Indian origin. Recently, molecular studies on the basis of disease-causing mutations and haploid DNA markers (i.e. mtDNA and Y-chromosome) supported the linguistic view. The presence of Indian-specific Y-chromosome haplogroup H1a1a-M82 and mtDNA haplogroups M5a1, M18 and M35b among Roma has corroborated that their South Asian origins and later admixture with Near Eastern and European populations. However, previous studies have left unanswered questions about the exact parental population groups in South Asia. Here we present a detailed phylogeographical study of Y-chromosomal haplogroup H1a1a-M82 in a data set of more than 10,000 global samples to discern a more precise ancestral source of European Romani populations. The phylogeographical patterns and diversity estimates indicate an early origin of this haplogroup in the Indian subcontinent and its further expansion to other regions. Tellingly, the short tandem repeat (STR) based network of H1a1a-M82 lineages displayed the closest connection of Romani haplotypes with the traditional scheduled caste and scheduled tribe population groups of northwestern India.


Two trees illustrate the results succinctly:

The bottom line:

- This particular Y chromosomal lineage which is highly diagnostic of South Asian origin in the Romani shows that the Romani seem to derive from the populations of northwest India

- Additionally, within these populations the Romani Y chromosomal lineages derive from the lower caste elements, the scheduled castes and scheduled tribes

But the above results don’t get directly at genome-wide admixture. The second paper does, using hundreds of thousands of markers to explore the Romani affinity to other populations. Reconstructing the Population History of European Romani from Genome-wide Data:

The Romani, the largest European minority group with approximately 11 million people…constitute a mosaic of languages, religions, and lifestyles while sharing a distinct social heritage. Linguistic…and genetic…studies have located the Romani origins in the Indian subcontinent. However, a genome-wide perspective on Romani origins and population substructure, as well as a detailed reconstruction of their demographic history, has yet to be provided. Our analyses based on genome-wide data from 13 Romani groups collected across Europe suggest that the Romani diaspora constitutes a single initial founder population that originated in north/northwestern India ∼1.5 thousand years ago (kya). Our results further indicate that after a rapid migration with moderate gene flow from the Near or Middle East, the European spread of the Romani people was via the Balkans starting ∼0.9 kya. The strong population substructure and high levels of homozygosity we found in the European Romani are in line with genetic isolation as well as differential gene flow in time and space with non-Romani Europeans. Overall, our genome-wide study sheds new light on the origins and demographic history of European Romani.

The plot to the left illustrates the relationship of the Romani to world-wide populations using multi-dimensional scaling, where genetic variation is decomposed into dimensions, and individuals are plotted on those dimensions. In short, the Romani exhibit a classic admixture cline pattern.That is, they are the products of a two-way admixture between populations which occupy distinct positions along a cline, and Romani individuals and populations are distributed along the cline in proportion to their admixture. One notable aspect is that the Romani are actually two clusters; one which manifests a strong ‘east’-'west’ distribution, and another which seems located purely within the European cluster. The latter seems to be the Welsh Romani, who in the neighbor-joining tree (see the supplements) fall on the same branch as European populations, as opposed to the other Romani, who form their own clade.

To drill down further you need to ascertain admixture with a model-based clustering algorithm. Ergo, ADMIXTURE. I’ve reedited the figure to illustrate the salient points. In particular, it is clear that the Roma populations except the Welsh have significant South Asian ancestry. The question is how much? To answer this question you need to know the source population in South Asia. A peculiar aspect of this plot is that the Romani have very little of the green ancestral component, which happens to be modal in the Middle East (not shown). This element happens to be highly enriched in many Pakistani populations, but not necessarily northwest Indian ones. Nevertheless, the issue that leaves me suspicious of this particular finding is that many of the European populations, in particular those groups (e.g., Balkans) which may have admixed with the Romani, have this element to extent not evident in one of their presumed ‘daughter’ populations. I wonder if perhaps the peculiarities of Romani inbreeding has skewed the allele frequency distribution so much that you get strangeness like this. I am not showing higher K’s because those break out with a Romani-cluster. Just like the Kalash-cluster this is to a great extent a feature of the long term endogamy of these communities. With high levels of drift the allele frequency of these groups moves into a very peculiar space in relation to their parental populations, but one must not become confused and assume that the Romani or Kalash are themselves appropriate independent clusters in the same way that Europeans or East Asians are.

Using various forms of admixture analysis the authors seem to conclude that the Balkan Romani are 30-50% South Asian. This seems in line with intuition. But that still leaves open the question of who those South Asians were. As I noted above the most thorough Y chromosomal data point to the lower caste elements of northwest India. What do the autosomes say?

I don’t want get into the technical details of how they tested the models, but it seems that one of the likely parental populations to the Romani had a close relationship to the Meghwal, a scheduled caste from northwest India. In other words, the autosome results align very well with the Y chromosomal inferences. Additionally, the models tested imply that the Romani likely left South Asian ~1,000 years before the present, which aligns well with what is known from the historical record (though this is a case where I put much more stock in the historical record than inferences from population genetic models; look at the intervals).

Finally, there is the question of inbreeding. One aspect of the Romani genome is jumps out you is that they have many long “runs-of-homozygosity” (ROH). This is totally expected, as decades of uniparental analyses suggested a great deal of population bottleneck events as the Romani spread throughout Europe. But the ROH patterns also unearth an interesting fact: some of the Balkan Romani clearly have recent European admixture, while the non-Balkan Romani had an initial period of admixture followed by endogamy. The latter scenario seems to resemble Askhenazi Jews, while the former would suggest that the boundary between Romani and non-Romani in the Balkans is more fluid than is sometimes portrayed.

So there we have it. The Romani derive from lower castes populations from the northwest Indian subcontinent who seem to have left ~1,000 years ago. Over time they admixed with local populations, and are now 50-70% non-South Asian, with some groups being ~90% European (e.g., Welsh Romani). And, they have a long history as an endogamous group, judging by their inbreeding.

The archaeologist, James Fallows, and Neandertals

By Razib Khan | November 17, 2012 10:10 pm

A month ago I posted Don’t trust an archaeologist about genetics, don’t trust a geneticist about archaeology, in response to James Fallows at At 5% Neanderthal, You Are an Outlier. Fallows has now put up a follow up, The Neanderthal Defense Committee Swings Into Action, where he links to my response post. This prompted the original archaeologist in question to reach out to me via email. I am posting the letter, with their permission, below.

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CATEGORIZED UNDER: Anthroplogy, Genetics

Why chimpanzees can donate blood in movies

By Razib Khan | October 23, 2012 1:07 am

There is a high likelihood that you know of which ABO blood group you belong to. I am A. My daughter is A. My father is B. My mother is A. I have siblings who are A, O, B, and AB. The inheritance is roughly Mendelian, with O being “recessive” to A and B (which are co-dominant with each other, ergo, AB). It is also generally common knowledge that O is a “universal donor,” while A and B can only give to individuals within their respective blood group and AB.

Because ABO was easy to assay it was one of the earliest Mendelian markers utilized in human genetics. In the first half of the 20th century while some anthropologists were measuring skulls, others were mapping out the frequency of A, B, and O. Today with much more robust genetic methods ABO has lost its old luster as a genetic marker, especially since there is a strong suspicion that the variants are strongly shaped by natural selection. This makes them only marginally useful for systematics, which rely upon loci which are honest mirrors of demographic history.

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Buddy can you spare a selective sweep

By Razib Khan | October 21, 2012 12:52 pm

The Pith: Natural selection comes in different flavors in its genetic constituents. Some of those constituents are more elusive than others. That makes “reading the label” a non-trivial activity.

As you may know when you look at patterns of variation in the genome of a given organism you can make various inferences from the nature of these patterns. But the power of those inferences is conditional on the details of the real demographic and evolutionary histories, as well as the assumptions made about the models one which is testing. When delving into the domain of population genomics some of the concepts and models may seem abstruse, but the reality is that such details are the stuff of which evolution is built. A new paper in PLoS Genetics may seem excessively esoteric and theoretical, but it speaks to very important processes which shape the evolutionary trajectory of a given population. The paper is titled Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation. Here’s the author summary:

Considerable effort has been devoted to detecting genes that are under natural selection, and hundreds of such genes have been identified in previous studies. Here, we present a method for extending these studies by inferring parameters, such as selection coefficients and the time when a selected variant arose. Of particular interest is the question whether the selective pressure was already present when the selected variant was first introduced into a population. In this case, the variant would be selected right after it originated in the population, a process we call selection from a de novo mutation. We contrast this with selection from standing variation, where the selected variant predates the selective pressure. We present a method to distinguish these two scenarios, test its accuracy, and apply it to seven human genes. We find three genes, ADH1B, EDAR, and LCT, that were presumably selected from a de novo mutation and two other genes, ASPM and PSCA, which we infer to be under selection from standing variation.

The dynamic which they refer to seems to be a reframing of the conundrum of detecting hard sweeps vs. soft sweeps. In the former you case have a new mutation, so its frequency is ~1/(2N). It is quickly subject to natural selection (though stochastic processes dominate at low frequencies, so probability of extinction is high), and adaptation drives the allele to fixation (or nearly to fixation). In the latter scenario you have a great deal of extant genetic variation, present in numerous different allelic variants. A novel selection pressure reshapes the frequency landscape, but you can not ascribe the genetic shift to only one allele. It is no surprise that the former is easier to model and detect than the latter. Much of the evolutionary genomics of the 2000s focused on hard sweeps from de novo mutations because they were low hanging fruit. The methods had reasonable power to detect them (as well as many false positives!). But of late many are suspecting that hard sweeps are not the full story, and that much of evolutionary genetic process may be characterized by a combination of hard sweeps, soft sweeps (from standing variation), various forms of negative selection, not to mention the plethora of possibilities which abound in the domain of balancing selection.

Many of the details of the paper may seem overly technical and opaque (and to be fair, I will say here that the figures are somewhat difficult to decrypt, though the subject is not one that lends itself to general clarity), but the major finding is straightforward, and illustrated in figure 4 (I’ve added labels):

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Yes, a young boy was forced from school for carrying cystic fibrosis alleles

By Razib Khan | October 18, 2012 9:19 pm

Update II: This comment sums up the pertinent issues.

Update: Please see comments below. This may be an infectious disease story, and not a genetic one.

When a reader sent me an email about the story, I assumed it was a rather sophisticated hoax. The short of it is that an 11 year old boy, Colman Chadam, has been pulled out of his school in Palo Alto because he carries alleles for cystic fibrosis, though he is asymptomatic (i.e., he has never manifested any symptoms of c.f.) administrators are worried that he might pose a risk to some students who do show progression of c.f. (bacterial infections can spread from child to child). As you probably know about 1 out of 30 people of European descent is a carrier for one of the many thousands of mutant variants for cystic fibrosis. The details of Colman Chadam’s results are not totally clear. Is he just a carrier? Or does he have two copies of cystic fibrosis, but somehow they differ enough that they can functionally complement each other?

We don’t know. But we do know that the lawyer from the school, Lenore Silverman, has stated that “The district is not willing to risk a potentially life-threatening illness among kids.” The risk here is non-existent. Not to be creepy, but does the school require that people with various venereal diseases also avoid the premises? With the small, but non-trivial, frequency of sexual abuse at school they too post a illness risk to the kids. In fact, more than Colman Chadam.

You can read everything at The San Francisco Chronicle. Perhaps you want to contact some of the staff at Jordan Middle School in Palo Alto. These people should be ashamed of themselves. I know we live in a litigious society, and being in education isn’t the easiest job, but we deserve better than this!

MORE ABOUT: Genetics

Introgressing toward becoming rice

By Razib Khan | October 4, 2012 12:24 am

Rice is a pretty big deal. There’s really no need to justify research on this crop. It feeds literally billions, so the funding will always flow. Would that we knew rice as well as we know C. elgans. After yesterday’s travesty of a paper on barley I thought that readers might find a new paper in Nature, A map of rice genome variation reveals the origin of cultivated rice, more interesting and illuminating. The authors used genomic sequencing, of varied coverage (i.e., very deep, repeated, and therefore accurate coverage vs. a single pass which is a very rough draft), to assess the relationship between Asian wild rice and two of the dominant domestic cultivars, indica (long-grain paddy rice) and japonica (short-grain dry cultivation rice). Presumably the two cultivars derive from a wild ancestor, but the details are still being hashed out.

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MORE ABOUT: Genetics, Genomics, Rice

Signal of Indo-Aryan admixture in South Indian Brahmins

By Razib Khan | September 29, 2012 12:59 am

I’ve mentioned a few times that the Reich lab has been finding suggestive evidence for admixture between indigenous South Asians and a West Eurasian group on the order of ~3,000 years before the present. The modal explanation is probably an Indo-Aryan intrusion. Dienekes used rolloff in ADMIXTOOLS to repeat these general findings. Specifically, he found signal for an admixture event analogous to one between non-Brahmin South Indians and Northern Europeans. I say analogous because I do not mean to imply that the admixture was exactly of this form. Rather, there are general resemblances in the genetic profiles across the four groups (i.e., Orcadian & North Kannadi, and population X and Y which merged to form South Indian Brahmins).

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CATEGORIZED UNDER: Human Genetics, Human Genomics
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The great Eurasian explosion

By Razib Khan | September 17, 2012 9:38 pm

Dr. Joseph Pickrell has updated his preprint, The genetic prehistory of southern Africa, with some more material on the Sandawe. I’ve explored the genetics of the Sandawe a bit using ADMIXTURE, so I jumped straight to the section on ROLLOFF:

…To further examine this, we turned to ROLLOFF. We used Dinka and French as representatives of the mixing populations (since date estimates are robust to improperly specified reference populations). The results are shown in Supplementary Figure S22. Both populations show a detectable curve, though the signal is much stronger in the Sandawe than in the Hadza. The implied dates are 89 generations (2500 years) ago for the Hadza and 66 generations (2000 years) ago for the Sandawe. These are qualitatively similar signals to those seen by Pagani et al. [65] in Ethiopian populations. There are two possible historical scenarios that could lead to these signals: either the Hadza and Sandawe both directly admixed with a western Eurasian population about 2,000 years ago, or they admixed with an east African population that was itself admixed with a western Eurasian population. The latter possibility would be consistent with known east African admixture into the Sandawe [16] .


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CATEGORIZED UNDER: Genetics, Genomics

What the substrate tells

By Razib Khan | September 16, 2012 8:26 pm

One of the weird things about genetics is that it encompasses both the abstract and the concrete. The formal and physical. You can talk to a geneticist who is mostly interested in details of molecular mechanisms, and is steeped in structural biology. For these people genes are specific and material things. In contrast there are other geneticists who focus more on genes as units of analysis. In this case genes are semantic labels for the mediators within an intersection of phenomena. Recall that genetics predates the knowledge of its concrete substrate by 50 years! By the 1920s Mendelian genetics had been fused with evolutionary biology to create a systematic framework in which we could understand the patterns of inheritance across the generations. In the 1950s the DNA revolution was upon us, but as W. D. Hamilton recalls this had only a minimal impact on the evolutionary genetic thinkers of the era. With the Lewontin and Hubby allozyme paper in the mid-1960s this sort of benign disciplinary evasion was no longer possible; the field of molecular evolution came into its own.*

Today with genomics these human-imposed artificialities are fading away. Consider the concept of genetic recombination. Originally an abstraction in a formal Mendelian system, today it is of great interest to molecular biologists who are curious as to its exact mechanism and purpose, and genomicists who are interested in the constraints upon the phenomenon due to its physical parameters (e.g., recombination hotspots). If we were to discover alien beings I assume that there would be some sort of genetics in an abstract sense. But would they package their genes in chromosomes? Would their complex organisms tend toward dioecy? I wouldn’t be surprised if the genetics of alien species have their own particular kinks subject to the contingent nature of the physical scaffolding of the process.

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Mutation: how about dividing by two?

By Razib Khan | September 12, 2012 1:27 am

There’s been a mild debate in the literature about the human mutation rate recently. I assume it will reach some consensus within the next few  years, but until then Nature Reviews Genetics has published something which lays out the implications in precise fashion for a slower mutation rate. Revising the human mutation rate: implications for understanding human evolution:

The four key points may be summarized as follows. First, the divergence between modern humans and both Neanderthals and Denisovans, which was originally estimated to be 272,000–435,000 years ago, is revised to 400,000–600,000 years ago. This is in better agreement with the range of estimated split times from mtDNA and also with the idea that the ancestral population of these groups may have been H. heidelbergensis. Second, for the split between the Khoe–San and other modern humans, revised estimates from nuclear genomic data suggest a divergence 250,000–300,000 years ago, older than single-locus estimates for the root of the human tree. Third, revised estimates of the separation time between Africans and non-Africans suggest that this predates the appearance of modern humans in Europe and Asia by up to 60,000 years. We have suggested a scenario of exodus from Africa via an intermediate population in East Africa and the Middle East, which may fit better with growing evidence for modern human occupation of the latter region before the wider colonization of Eurasia and may provide a longer interval for Neanderthal admixture with non-African populations. Finally, revised split times of 40,000–80,000 years ago for Europeans and Asians agree better with the palaeoanthropological record and with estimates from mtDNA.

The authors do understand that their phylogenetic model impacts their inferences. If there was a lot of archaic admixture into the Khoe and Bushmen their divergence from other modern humans might be inflated. But it is always striking to me that there is this strange result that populations like the Yoruba might be in a clade with non-Africans against Khoe and Bushmen.

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Genes, a gene, genes….

By Razib Khan | September 6, 2012 1:38 am

I spend some time thinking about genetic architecture. If you read media accounts of genetics you wouldn’t know there was such a thing. Why not? Because it makes a narrative rather messy and complex. Rather, a better story is one where you have a gene-for-something. But the gene-for-something model is probably most useful in the domain of recessive diseases. In these cases you have a mutant variant which has a powerful effect when found in two copies in an individual. The distinction between the disease state and the “wild” state is rather straightforward. Not so with many “complex traits.”

Two papers came into my RSS feed which illustrate two ends of this dynamic. First, A Sexual Ornament in Chickens Is Affected by Pleiotropic Alleles at HAO1 and BMP2, Selected during Domestication:

The genetic analysis of phenotypes and the identification of the causative underlying genes remain central to molecular and evolutionary biology. By utilizing the domestication process, it is possible to exploit the large differences between domesticated animals and their wild counterparts to study both this and the mechanism of domestication itself. Domestication has been central to the advent of modern civilization; and yet, despite domesticated animals displaying similar adaptations in morphology, physiology, and behaviour, the genetic basis of these changes are unknown. In addition, though sexual selection theory has been the subject of a vast amount of study, very little is known about which genes are underpinning such traits. We have generated multiple intercrosses and advanced intercrosses based on wild-derived and domestic chickens to fine-map genomic regions affecting a sexual ornament. These regions have been over-laid with putative selective sweeps identified in domestic chickens and found to be significantly associated with them. By using expression QTL analysis, we show that two genes in one region, HAO1 and BMP2, are controlling multiple aspects of the domestication phenotype, from a sexual ornament to multiple life history traits. This demonstrates the importance of pleiotropy (or extremely close linkage) in controlling these genetic changes.

A nice elegant solution. Strong bout of selection, and a response on two genes, which also generates a lot of side effect phenotypes. This section in particular intrigued me:

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CATEGORIZED UNDER: Genetics, Genomics
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Me & my 0.55 brother against my 0.45 brother

By Razib Khan | September 4, 2012 11:41 pm

One of the more fascinating things about getting much of your child’s pedigree genotyped is that one can ascertain true relatedness to various relatives, rather than just expected relatedness. For example, 28% of her genome is identical by descent from my father, while 22% is from my mother. She is 26% identical by descent with one uncle, and 24% with another. More practically, the understanding of patterns realized and concrete genetic relatedness within families allows us another avenue into teasing apart heritability. Though this method has been around for more than half-a-decade, I find it curious that when I post on it some commenters immediately make objections to twin studies. Why? Because they assume that the analysis had to be a twin study because they don’t know of the genomic methodology!

But on a broader evolutionary scale, does this matter? Two of my siblings have a relatedness of 41%. In other words, as you can see in the histogram there is a wide variation in relatedness. Might this perhaps impact social relations? One can imagine genetically more similar siblings aligning against those who are dissimilar. Or not. I am skeptical that this would apply to humans, but I do wonder about organisms with larger broods. If we don’t find much variation on the scale of siblings, despite genetic variation (and therefore, likely phenotypic tells of similarity), then I would hazard to suggest that inclusive fitness is not quite the razor sharp discerning tool that some posit it is. Rather, it is part of the broader swiss army knife of behavioral ecology.

MORE ABOUT: Genetics, Heritability

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