Another piece of evidence in favor of the claim that mtDNA variation may have been shaped by natural selection.
AIDS. 2008 Nov 30;22(18):2429-2439.
Mitochondrial DNA haplogroups influence AIDS progression.
Hendrickson SL, Hutcheson HB, Ruiz-Pesini E, Poole JC, Lautenberger J, Sezgin E, Kingsley L, Goedert JJ, Vlahov D, Donfield S, Wallace DC, Oʼbrien SJ.
OBJECTIVE:: Mitochondrial function plays a role in both AIDS progression and HAART toxicity; therefore, we sought to determine whether mitochondrial DNA variation revealed novel AIDS restriction genes, particularly as mitochondrial DNA single-nucleotide polymorphisms are known to influence regulation of oxidative phosphorylation, reactive oxygen species production, and apoptosis. DESIGN:: This is a retrospective cohort study. METHODS:: We performed an association study of mitochondrial DNA haplogroups among 1833 European American HIV-1 patients from five US cohorts: the Multicenter AIDS Cohort Study, the San Francisco City Clinic Study, Hemophilia Growth and Development Study, the Multicenter Hemophilia Cohort Study, and the AIDS Linked to Intravenous Experiences cohort to determine whether the mitochondrial DNA haplogroup correlated with AIDS progression rate. RESULTS:: Mitochondrial DNA haplogroups J and U5a were elevated among HIV-1 infected people who display accelerated progression to AIDS and death. Haplogroups Uk, H3, and IWX appeared to be highly protective against AIDS progression. CONCLUSION:: The associations found in our study appear to support a functional explanation by which mitochondrial DNA variation among haplogroups, influencing ATP production, reactive oxygen species generation, and apoptosis, is correlated to AIDS disease progression; however, repeating these results in cohorts with different ethnic backgrounds would be informative. These data suggest that mitochondrial genes are important indicators of AIDS disease progression in HIV-1 infected persons.
Link
November 14, 2008
mtDNA and goat domestication
Wikiedia artiles on goat and bezoar.The lowly goat (aiga) has played a great role in Greek history: the Aegean Sea (from Aegeus, the father of Theseus) is named after it. So were Aigai, the ancient Macedonian capital coinciding with the archaeological site of Vergina. The ancestor of the Dorians was King Aegimius, whose mythological story of contact with Hercules parallels the historical relationship between the Dorians and their Heraclid rulers. The Aegos Potami (goat rivers) is one of many aig- sites, famous among other things as the landing site of a meteor, according to the Parian Marble.
And, of course, the he-goat (tragos), associated with the god Dionysus, played its role in the Greek invention of theater, and in particular tragedy by Thespis.
Proc Natl Acad Sci U S A. 2008 Nov 12. [Epub ahead of print]
The goat domestication process inferred from large-scale mitochondrial DNA analysis of wild and domestic individuals.
Naderi S, Rezaei HR, Pompanon F, Blum MG, Negrini R, Naghash HR, Balkiz O, Mashkour M, Gaggiotti OE, Ajmone-Marsan P, Kence A, Vigne JD, Taberlet P.
The emergence of farming during the Neolithic transition, including the domestication of livestock, was a critical point in the evolution of human kind. The goat (Capra hircus) was one of the first domesticated ungulates. In this study, we compared the genetic diversity of domestic goats to that of the modern representatives of their wild ancestor, the bezoar, by analyzing 473 samples collected over the whole distribution range of the latter species. This partly confirms and significantly clarifies the goat domestication scenario already proposed by archaeological evidence. All of the mitochondrial DNA haplogroups found in current domestic goats have also been found in the bezoar. The geographic distribution of these haplogroups in the wild ancestor allowed the localization of the main domestication centers. We found no haplotype that could have been domesticated in the eastern half of the Iranian Plateau, nor further to the east. A signature of population expansion in bezoars of the C haplogroup suggests an early domestication center on the Central Iranian Plateau (Yazd and Kerman Provinces) and in the Southern Zagros (Fars Province), possibly corresponding to the management of wild flocks. However, the contribution of this center to the current domestic goat population is rather low (1.4%). We also found a second domestication center covering a large area in Eastern Anatolia, and possibly in Northern and Central Zagros. This last domestication center is the likely origin of almost all domestic goats today. This finding is consistent with archaeological data identifying Eastern Anatolia as an important domestication center.
Link
Tribute to W. W. Howells
The Yearbook of Physical Anthropology has a tribute to the late W. W. Howells. One of his greatest achievements is certainly his meticulously collected worldwide cranial sample which is available online, and includes measurements on both recent humans of the last few millennia, as well as several earlier samples that were available to him. This sample is routinely used even today by anthropologists studying human variation, or trying to place historical hominids into context.
I have previously used this dataset in some earlier posts (search "Howells") and in my article on Model-Based Clustering of World Craniometric Variation (also as pdf), in which I repeated his clustering of world human populations, but using a computationally expensive model-based clustering algorithm (conceptually similar to STRUCTURE in genetics) that was not available during his time.
One of his lesser achievements was being the mentor at Harvard of the recently deceased author Michael Crichton.
American Journal of Physical Anthropology
Volume 137 Issue S47, Pages 118 - 126
From the shoulders of a giant: Perspectives on the legacy of William White Howells (1908-2005)
Laurie R. Godfrey
Abstract
William White Howells was one of the intellectual giants of the discipline of biological anthropology during the twentieth century. He was a devoted student of Earnest A. Hooton; yet he played a central role in directing the discipline away from the typological thinking that infused the work of his predecessor, and toward the population perspective that characterizes the field today. An original and productive scholar with diverse interests, his influence was extraordinary not merely because of his brilliance, but also because of the kind of mentor he was. Almost two dozen graduate students, and countless others with whom he interacted in various capacities, have carried Howells' legacy into the twenty-first century.
Link
I have previously used this dataset in some earlier posts (search "Howells") and in my article on Model-Based Clustering of World Craniometric Variation (also as pdf), in which I repeated his clustering of world human populations, but using a computationally expensive model-based clustering algorithm (conceptually similar to STRUCTURE in genetics) that was not available during his time.
One of his lesser achievements was being the mentor at Harvard of the recently deceased author Michael Crichton.
American Journal of Physical Anthropology
Volume 137 Issue S47, Pages 118 - 126
From the shoulders of a giant: Perspectives on the legacy of William White Howells (1908-2005)
Laurie R. Godfrey
Abstract
William White Howells was one of the intellectual giants of the discipline of biological anthropology during the twentieth century. He was a devoted student of Earnest A. Hooton; yet he played a central role in directing the discipline away from the typological thinking that infused the work of his predecessor, and toward the population perspective that characterizes the field today. An original and productive scholar with diverse interests, his influence was extraordinary not merely because of his brilliance, but also because of the kind of mentor he was. Almost two dozen graduate students, and countless others with whom he interacted in various capacities, have carried Howells' legacy into the twenty-first century.
Link
Differences between Early and Late Upper Paleolithic Europeans
American Journal of Physical Anthropology
Volume 137 Issue S47, Pages 70 - 99
Hunters of the Ice Age: The biology of Upper Paleolithic people
Brigitte M. Holt, Vincenzo Formicola
Abstract
The Upper Paleolithic represents both the phase during which anatomically modern humans appeared and the climax of hunter-gatherer cultures. Demographic expansion into new areas that took place during this period and the diffusion of burial practices resulted in an unprecedented number of well-preserved human remains. This skeletal record, dovetailed with archeological, environmental, and chronological contexts, allows testing of hypotheses regarding biological processes at the population level. In this article, we review key studies about the biology of Upper Paleolithic populations based primarily on European samples, but integrating information from other areas of the Old World whenever possible. Data about cranial morphology, skeletal robusticity, stature, body proportions, health status, diet, physical activity, and genetics are evaluated in Late Pleistocene climatic and cultural contexts. Various lines of evidence delineate the Last Glacial Maximum (LGM) as a critical phase in the biological and cultural evolution of Upper Paleolithic populations. The LGM, a long phase of climatic deterioration culminating around 20,000 BP, had a profound impact on the environment, lifestyle, and behavior of human groups. Some of these effects are recorded in aspects of skeletal biology of these populations. Groups living before and after the LGM, Early Upper Paleolithic (EUP) and Late Upper Paleolithic (LUP), respectively, differ significantly in craniofacial dimensions, stature, robusticity, and body proportions. While paleopathological and stable isotope data suggest good health status throughout the Upper Paleolithic, some stress indicators point to a slight decline in quality of life in LUP populations. The intriguing and unexpected incidence of individuals affected by congenital disorders probably indicates selective burial practices for these abnormal individuals. While some of the changes observed can be explained through models of biocultural or environmental adaptation (e.g., decreased lower limb robusticity following decreased mobility; changes in body proportions along with climatic change), others are more difficult to explain. For instance, craniodental and upper limb robusticity show complex evolutionary patterns that do not always correspond to expectations. In addition, the marked decline in stature and the mosaic nature of change in body proportions still await clarifications. These issues, as well as systematic analysis of specific pathologies and possible relationships between genetic lineages, population movements and cultural complexes, should be among the goals of future research.
Link
Volume 137 Issue S47, Pages 70 - 99
Hunters of the Ice Age: The biology of Upper Paleolithic people
Brigitte M. Holt, Vincenzo Formicola
Abstract
The Upper Paleolithic represents both the phase during which anatomically modern humans appeared and the climax of hunter-gatherer cultures. Demographic expansion into new areas that took place during this period and the diffusion of burial practices resulted in an unprecedented number of well-preserved human remains. This skeletal record, dovetailed with archeological, environmental, and chronological contexts, allows testing of hypotheses regarding biological processes at the population level. In this article, we review key studies about the biology of Upper Paleolithic populations based primarily on European samples, but integrating information from other areas of the Old World whenever possible. Data about cranial morphology, skeletal robusticity, stature, body proportions, health status, diet, physical activity, and genetics are evaluated in Late Pleistocene climatic and cultural contexts. Various lines of evidence delineate the Last Glacial Maximum (LGM) as a critical phase in the biological and cultural evolution of Upper Paleolithic populations. The LGM, a long phase of climatic deterioration culminating around 20,000 BP, had a profound impact on the environment, lifestyle, and behavior of human groups. Some of these effects are recorded in aspects of skeletal biology of these populations. Groups living before and after the LGM, Early Upper Paleolithic (EUP) and Late Upper Paleolithic (LUP), respectively, differ significantly in craniofacial dimensions, stature, robusticity, and body proportions. While paleopathological and stable isotope data suggest good health status throughout the Upper Paleolithic, some stress indicators point to a slight decline in quality of life in LUP populations. The intriguing and unexpected incidence of individuals affected by congenital disorders probably indicates selective burial practices for these abnormal individuals. While some of the changes observed can be explained through models of biocultural or environmental adaptation (e.g., decreased lower limb robusticity following decreased mobility; changes in body proportions along with climatic change), others are more difficult to explain. For instance, craniodental and upper limb robusticity show complex evolutionary patterns that do not always correspond to expectations. In addition, the marked decline in stature and the mosaic nature of change in body proportions still await clarifications. These issues, as well as systematic analysis of specific pathologies and possible relationships between genetic lineages, population movements and cultural complexes, should be among the goals of future research.
Link
Later Stone Age South African Hunter gatherers and Herders as a single population
Related regarding a pastoralist migration to South Africa: Y-chromosomal evidence of a pastoralist migration through Tanzania to southern Africa.
Journal of Archeological Science doi: 10.1016/j.jas.2008.11.001
Craniometric evidence for South African Later Stone Age herders and hunter-gatherers being a single biological population
Deano D. Stynder
Abstract
Later Stone Age (LSA) hunter-gatherers and herders co-existed in South Africa during the last 2,000 years. In spite of being the focus of intensive research over the years, the biological status and origins of the herders are still unclear. Did they represent a genetically distinct immigrant population who remained separate from the indigenous hunter-gatherers, or where they indigenous hunter-gatherers who took up herding after contact with herders, probably in northern Botswana? Here, this issue is investigated using craniometric data collected on a large sample of individually dated human crania from coastal LSA context. Mahalanobis distances (D), calculated from the raw metric data, show that there was a small increase in inter-individual craniofacial variation after the introduction of herding at c. 2,000 BP. Here it is argued that this small increase in variation is neither consistent with a largescale immigration of genetically distinct herders into South Africa, or the long-term coexistence of two genetically distinct populations. Two alternative explanations fit the data better: (1) herding entered South Africa via the small-scale immigration of genetically distinct herders; and (2) local hunter-gatherer populations adopted herding after coming in contact with herders in northern Botswana. While small-scale immigration would not have had a major influence on the local gene pool, it would have increased variation to some extent as immigrants mixed with local populations. If small-scale external gene flow was not a factor in the introduction of herding, secular issues related to the introduction of herding could explain the increased variation in post-2,000 BP populations.
Link
Journal of Archeological Science doi: 10.1016/j.jas.2008.11.001
Craniometric evidence for South African Later Stone Age herders and hunter-gatherers being a single biological population
Deano D. Stynder
Abstract
Later Stone Age (LSA) hunter-gatherers and herders co-existed in South Africa during the last 2,000 years. In spite of being the focus of intensive research over the years, the biological status and origins of the herders are still unclear. Did they represent a genetically distinct immigrant population who remained separate from the indigenous hunter-gatherers, or where they indigenous hunter-gatherers who took up herding after contact with herders, probably in northern Botswana? Here, this issue is investigated using craniometric data collected on a large sample of individually dated human crania from coastal LSA context. Mahalanobis distances (D), calculated from the raw metric data, show that there was a small increase in inter-individual craniofacial variation after the introduction of herding at c. 2,000 BP. Here it is argued that this small increase in variation is neither consistent with a largescale immigration of genetically distinct herders into South Africa, or the long-term coexistence of two genetically distinct populations. Two alternative explanations fit the data better: (1) herding entered South Africa via the small-scale immigration of genetically distinct herders; and (2) local hunter-gatherer populations adopted herding after coming in contact with herders in northern Botswana. While small-scale immigration would not have had a major influence on the local gene pool, it would have increased variation to some extent as immigrants mixed with local populations. If small-scale external gene flow was not a factor in the introduction of herding, secular issues related to the introduction of herding could explain the increased variation in post-2,000 BP populations.
Link
November 13, 2008
Warfare and human evolution
The New Scientist has an interesting article on war and its role in human evolution (How warfare shaped human evolution )
Now a new theory is emerging that challenges the prevailing view that warfare is a product of human culture and thus a relatively recent phenomenon. For the first time, anthropologists, archaeologists, primatologists, psychologists and political scientists are approaching a consensus. Not only is war as ancient as humankind, they say, but it has played an integral role in our evolution.Here is the website of this conference: Evolutionary Perspectives on War Conference. More from the New Scientist article:
...
These ideas emerged at a conference last month on the evolutionary origins of war at the University of Oregon in Eugene. "The picture that was painted was quite consistent," says Mark Van Vugt, an evolutionary psychologist at the University of Kent, UK. "Warfare has been with us for at least several tens, if not hundreds, of thousands of years."
Studies suggest that warfare accounts for 10 per cent or more of all male deaths in present-day hunter-gatherers. ... Primatologists have known for some time that organised, lethal violence is common between groups of chimpanzees, our closest relatives. ... Such raids are possible because humans and chimps, unlike most social mammals, often wander away from the main group to forage singly or in smaller groups, says Wrangham. ... Several participants presented the strongest evidence yet that males - whose larger and more muscular bodies make them better suited for fighting - have evolved a tendency towards aggression outside the group but cooperation within it. ... Aggression in women, she notes, tends to take the form of verbal rather than physical violence, and is mostly one on one.
...
Some of this behaviour could arguably be attributed to conscious mental strategies, but anthropologist Mark Flinn of the University of Missouri at Columbia has found that group-oriented responses occur on the hormonal level, too. He found that cricket players on the Caribbean island of Dominica experience a testosterone surge after winning against another village. But this hormonal surge, and presumably the dominant behaviour it prompts, was absent when the men beat a team from their own village, Flinn told the conference. "You're sort of sending the signal that it's play. You're not asserting dominance over them," he says. Similarly, the testosterone surge a man often has in the presence of a potential mate is muted if the woman is in a relationship with his friend. Again, the effect is to reduce competition within the group, says Flinn. "We really are different from chimpanzees in our relative amount of respect for other males' mating relationships."
...
Though women seem to help broker harmony within groups, says Van Vugt, men may be better at peacekeeping between groups.
November 12, 2008
Ancient DNA damage and phylogenetic histories
It is becoming more commonplace (example) of sampling large numbers of ancient individuals from natural populations. Unfortunately, ancient DNA suffers from potential damage, so what appears to be an ancient DNA sequence may contain both differences from current sequences that are due to evolution (changes in the gene pool over time), but also due to damage (changes in the ancient population's DNA remnants over time).
A way to deal with damage is to limit oneself to the study of genetic changes that are resilient to it, e.g., transversions over the commoner transitions. But, by doing so, the statistical power is diminished (less data is used). What the authors of this paper do, is try to use the full ancient DNA data, while accounting for the effects of damage in a systematic way. Their conclusions -for their test case- is that its overall effect is not very pronounced.
Molecular Biology and Evolution, doi:10.1093/molbev/msn256
Accommodating the effect of ancient DNA damage on inferences of demographic histories
Andrew Rambaut et al.
Abstract
DNA sequences extracted from ancient remains are increasingly used to generate large population data sets, often spanning tens of thousands of years of population history. Bayesian coalescent methods such as those implemented in the software package BEAST can be used to estimate the demographic history of these populations, sometimes resulting in complex scenarios of fluctuations in population size, which can be correlated with the timing of environmental events, such as glaciations. Recently, however, Axelsson et al. (2008) claimed that many of these complex demographic trends are likely to be the result of post-mortem DNA damage, a problem that they investigate by removing all sites involving transitions from ancient sequences prior to analysis. When this solution is applied to a previously published data set of Pleistocene bison, they show that the demographic signal of population expansion and decline disappears. While some apparently segregating mutations in ancient sequences may be due to post-mortem damage, we argue that discarding the data will result in loss of power to detect patterns of population change. Instead, to accommodate this problem, we implement a model in which sequences are the result of a joint process of molecular evolution and post-mortem DNA damage within a probabilistic inference framework. Through simulation, we demonstrate the ability of this model to accurately recover evolutionary parameters, demographic history and DNA damage rates. When this model is applied to the bison data set, we find that the rate of DNA damage is significant but low, and that the reconstruction of population size history is nearly identical to previously published estimates.
Link
A way to deal with damage is to limit oneself to the study of genetic changes that are resilient to it, e.g., transversions over the commoner transitions. But, by doing so, the statistical power is diminished (less data is used). What the authors of this paper do, is try to use the full ancient DNA data, while accounting for the effects of damage in a systematic way. Their conclusions -for their test case- is that its overall effect is not very pronounced.
Molecular Biology and Evolution, doi:10.1093/molbev/msn256
Accommodating the effect of ancient DNA damage on inferences of demographic histories
Andrew Rambaut et al.
Abstract
DNA sequences extracted from ancient remains are increasingly used to generate large population data sets, often spanning tens of thousands of years of population history. Bayesian coalescent methods such as those implemented in the software package BEAST can be used to estimate the demographic history of these populations, sometimes resulting in complex scenarios of fluctuations in population size, which can be correlated with the timing of environmental events, such as glaciations. Recently, however, Axelsson et al. (2008) claimed that many of these complex demographic trends are likely to be the result of post-mortem DNA damage, a problem that they investigate by removing all sites involving transitions from ancient sequences prior to analysis. When this solution is applied to a previously published data set of Pleistocene bison, they show that the demographic signal of population expansion and decline disappears. While some apparently segregating mutations in ancient sequences may be due to post-mortem damage, we argue that discarding the data will result in loss of power to detect patterns of population change. Instead, to accommodate this problem, we implement a model in which sequences are the result of a joint process of molecular evolution and post-mortem DNA damage within a probabilistic inference framework. Through simulation, we demonstrate the ability of this model to accurately recover evolutionary parameters, demographic history and DNA damage rates. When this model is applied to the bison data set, we find that the rate of DNA damage is significant but low, and that the reconstruction of population size history is nearly identical to previously published estimates.
Link
November 11, 2008
Belgian Spy Neanderthals 36,000 years BP old
American Journal of Physical Anthropology 10.1002/ajpa.20954
New data on the late Neandertals: Direct dating of the Belgian Spy fossils
Patrick Semal et al.
Abstract
In Eurasia, the period between 40,000 and 30,000 BP saw the replacement of Neandertals by anatomically modern humans (AMH) during and after the Middle to Upper Paleolithic transition. The human fossil record for this period is very poorly defined with no overlap between Neandertals and AMH on the basis of direct dates. Four new 14C dates were obtained on the two adult Neandertals from Spy (Belgium). The results show that Neandertals survived to at least ≈ 36,000 BP in Belgium and that the Spy fossils may be associated to the Lincombian-Ranisian-Jerzmanowician, a transitional techno-complex defined in northwest Europe and recognized in the Spy collections. The new data suggest that hypotheses other than Neandertal acculturation by AMH may be considered in this part of Europe.
Link
New data on the late Neandertals: Direct dating of the Belgian Spy fossils
Patrick Semal et al.
Abstract
In Eurasia, the period between 40,000 and 30,000 BP saw the replacement of Neandertals by anatomically modern humans (AMH) during and after the Middle to Upper Paleolithic transition. The human fossil record for this period is very poorly defined with no overlap between Neandertals and AMH on the basis of direct dates. Four new 14C dates were obtained on the two adult Neandertals from Spy (Belgium). The results show that Neandertals survived to at least ≈ 36,000 BP in Belgium and that the Spy fossils may be associated to the Lincombian-Ranisian-Jerzmanowician, a transitional techno-complex defined in northwest Europe and recognized in the Spy collections. The new data suggest that hypotheses other than Neandertal acculturation by AMH may be considered in this part of Europe.
Link
November 10, 2008
HGDP selection browser @ the Pritchard Lab
Genetic future points me towards a tool for browsing the HGDP 650K SNP data. This seems to be a great resource for interacting with the cumbersome HGDP data, and it will prove useful to check up for oneself "genes in the news". So, I suggest that you go read this post which places the tool in context.
November 09, 2008
"War of the Gods" vs. "Clash of the Titans"
"War of the Gods" is supposed to be a story about Theseus and "Clash of Titans" a story about Perseus. If a new Hercules movie materializes, then there may a movie about each of the major pre-Trojan Greek heroes in the works. And, apparently, NBC has a Jason and the Argonauts type TV project in the works. Personally, I'm more excited about seeing Xenophon's Anabasis or the 300 sequel than these other projects, but let's hope that at least 1 or 2 of them will be good like 300 and the Odyssey, and fewer of them mediocre like Alexander or Helen of Troy, or plain laughable like Troy.
Variety reports:
Variety reports:
Relativity Media is negotiating with Henry Cavill ("The Tudors") to star as Theseus in the Tarsem Singh-directed "War of the Gods."
At the same time, Warner Bros. is in talks with Sam Worthington to play the role of Perseus in the Louis Leterrier-directed "Clash of the Titans."
Deals for both actors are expected to be worked out, keeping the Greek mythology-themed projects on a parallel track. Both films are expected to begin production by late winter or early spring.
The projects have different plots, but each film will be made for under $100 million because the visual effects will be accomplished using the greenscreen techniques that made "300" so visually arresting.
Relativity got in the Greek game last summer when it bought the Charley and Vlas Parlapanides-scripted "War of the Gods" (Daily Variety, June 26).
Hollywood Gang's Gianni Nunnari and Canton Prods.' Mark Canton are producing with Ryan Kavanaugh.
At the same time, "The Incredible Hulk" helmer Leterrier committed to WB's "Clash of the Titans," a remake of the 1981 film that tells the story of Zeus son Perseus' journey and battles against Medusa. Scripted by Lawrence Kasdan, the WB film is a co-production with Legendary Pictures, produced by Basil Iwanyk of Thunder Road and Kevin De La Noy.
Cavill is best known for his work on Showtime's "The Tudors" but was also on the shortlist to play the Man of Steel in "Superman Returns."
Worthington, one of the finalists for the James Bond role that went to Daniel Craig, is starring for director James Cameron in "Avatar" and plays a pivotal role in the McG-directed "Terminator Salvation."
November 07, 2008
Sexual orientation of parents does affect their children
I can't say I am surprised by the findings of this evaluation. The whole issue seems to be a classic example of scientific-political mutualism, in which (i) common sense-toppling research is produced by scientists, who overlook some details that go against their own preferences and/or overstate the significance of their findings. (ii) These isolated results are then packaged into a review, which further boosts their significance. (iii) At some point, the media get hold of the supposed new scientific truth and start reinforcing it, making it the new public "common sense". (iv) More reviews and popular articles appear, parroting the new consensus, while opposite views are ridiculed and suppressed with a loud "science says otherwise". But (v) continuing new science and critical thinking undermines the new common sense. The final step, yet to be realized in this case, (vi) is the collapse of the new consensus and the re-affirmation of something closer to the original common sense.
Psychol Rep. 2008 Aug;103(1):275-304.
Re-evaluation of the "no differences" hypothesis concerning gay and lesbian parenting as assessed in eight early (1979-1986) and four later (1997-1998) dissertations.
Schumm WR.
Academic and policy effects of eight early dissertations on gay and lesbian parenting are discussed with a focus on their having been cited at least 234 times in over 50 literature reviews, beginning with Gottman in 1989 and 1990. Most literature reviews, referencing these eight early dissertations and agreeing with Gottman's early conclusions, have reiterated the theme that parenting by gay men or lesbians has outcomes no different than parenting by heterosexual parents. Here it is proposed that certain potential adverse findings may have been obscured by suppressor effects which could have been evaluated had multivariate analyses been implemented. Further, several adverse findings were detected by reanalyzing data where sufficient information was yet available. Some of the dissertations' results (absent controls for social desirability and other differences between homosexual and heterosexual parents) supported the 2001 "no differences" hypothesis discussed by Stacey and Biblarz. Yet, differences were also observed, including some evidence in more recent dissertations, suggesting that parental sexual orientation might be associated with children's later sexual orientation and adult attachment style, among other outcomes. Odds ratios associated with some of the apparent effects were substantial in magnitude as well as statistically significant. Also, more recent research on gay and lesbian parenting continues to be flawed by many of the same limitations as previous research in this area of study, including overlooked suppressor effects.
Link
Psychol Rep. 2008 Aug;103(1):275-304.
Re-evaluation of the "no differences" hypothesis concerning gay and lesbian parenting as assessed in eight early (1979-1986) and four later (1997-1998) dissertations.
Schumm WR.
Academic and policy effects of eight early dissertations on gay and lesbian parenting are discussed with a focus on their having been cited at least 234 times in over 50 literature reviews, beginning with Gottman in 1989 and 1990. Most literature reviews, referencing these eight early dissertations and agreeing with Gottman's early conclusions, have reiterated the theme that parenting by gay men or lesbians has outcomes no different than parenting by heterosexual parents. Here it is proposed that certain potential adverse findings may have been obscured by suppressor effects which could have been evaluated had multivariate analyses been implemented. Further, several adverse findings were detected by reanalyzing data where sufficient information was yet available. Some of the dissertations' results (absent controls for social desirability and other differences between homosexual and heterosexual parents) supported the 2001 "no differences" hypothesis discussed by Stacey and Biblarz. Yet, differences were also observed, including some evidence in more recent dissertations, suggesting that parental sexual orientation might be associated with children's later sexual orientation and adult attachment style, among other outcomes. Odds ratios associated with some of the apparent effects were substantial in magnitude as well as statistically significant. Also, more recent research on gay and lesbian parenting continues to be flawed by many of the same limitations as previous research in this area of study, including overlooked suppressor effects.
Link
November 06, 2008
In search of the Hidden Heritability
Nature has a very interesting high level survey of the problem of the "hidden heritability". While many traits such as height, autism, or schizophrenia are known to be significantly heritable, recent genome scans with high-density microarray chips, that look at hundreds of thousands of DNA polymorphisms, have failed to produce any significant results.
So, if these traits are in our genes, how come we can't find them there?
The article does a great job at identifying the possible ways to find the "hidden heritability". Here they are, in my own words:
1. Look at more DNA spots
There is a long way between the million or so DNA bases covered by current microarray chips and the whole human genome. Because of linkage disequilibrium, i.e., DNA's propensity to be cut and inherited in large chunks, and not small pieces, you can often tell the value of a marker by looking at nearby markers. But, still, you don't really know until you look. So, denser microarrays, or even whole genome sequences may uncover some of the hidden heritability.
2. Look at more people
Associations between traits and genes are established by statistics. To find a weak association, or an association between a not-so-common variant and the trait in question, you need a large sample. So, if the hidden heredity is hidden away in markers that are beyond your statistical power, you can simply increase this power: sample more people.
3. Look at copy-number variations (CNVs)
Any two individuals don't just have single-letter differences, but also structural changes, where an individual may have more or fewer copies of entire chunks of DNA. So, by looking at single nucleotides you are examining one source of human variation, but missing another chunk of it that may as important.
3. Study gene-gene interactions
Genes form complex networks of interaction. If you flip a SNP from C to T, you don't always get the same effect on the phenotype. This flip may increase, decrease, or leave unaffected, your risk for a disease, depending on what other genes you have. This epistatic interaction of genes makes it difficult to detect associations. It's a lot easier to study the individual effects of 2N alleles at N genes than it is to study the effects of 2N possible combinations.
4. Don't trust heritability estimates
What if inherited conditions thought to be genetic aren't really genetic, because of epigenetic modifications of gene expression, or shared environments (e.g., in the womb) that aren't accounted for?
5. Don't trust diagnoses of conditions
If you want to find a correlation between a gene G and a trait T, you'd better be sure what T actually is. If it's a whole set of different behaviors, conveniently bundled into a condition T (such as schizophrenia), then you're in trouble, since each of these conditions may have its own causative agent. Many major diseases may be caused by more than one underlying condition, with a different genetic background. So, if you are seeking to find the common thread between people with trait T, you might not find it because there is no common thread!
My guess is that the bulk of the missing heritability is to be found in three sources:
Some related posts on the limits of genome-wide association studies: on intelligence, on height and body mass index, and on CNVs.
(*) Incidentally, this is why the population replacement rate is more than 2 children per woman.
So, if these traits are in our genes, how come we can't find them there?
The article does a great job at identifying the possible ways to find the "hidden heritability". Here they are, in my own words:
1. Look at more DNA spots
There is a long way between the million or so DNA bases covered by current microarray chips and the whole human genome. Because of linkage disequilibrium, i.e., DNA's propensity to be cut and inherited in large chunks, and not small pieces, you can often tell the value of a marker by looking at nearby markers. But, still, you don't really know until you look. So, denser microarrays, or even whole genome sequences may uncover some of the hidden heritability.
2. Look at more people
Associations between traits and genes are established by statistics. To find a weak association, or an association between a not-so-common variant and the trait in question, you need a large sample. So, if the hidden heredity is hidden away in markers that are beyond your statistical power, you can simply increase this power: sample more people.
3. Look at copy-number variations (CNVs)
Any two individuals don't just have single-letter differences, but also structural changes, where an individual may have more or fewer copies of entire chunks of DNA. So, by looking at single nucleotides you are examining one source of human variation, but missing another chunk of it that may as important.
3. Study gene-gene interactions
Genes form complex networks of interaction. If you flip a SNP from C to T, you don't always get the same effect on the phenotype. This flip may increase, decrease, or leave unaffected, your risk for a disease, depending on what other genes you have. This epistatic interaction of genes makes it difficult to detect associations. It's a lot easier to study the individual effects of 2N alleles at N genes than it is to study the effects of 2N possible combinations.
4. Don't trust heritability estimates
What if inherited conditions thought to be genetic aren't really genetic, because of epigenetic modifications of gene expression, or shared environments (e.g., in the womb) that aren't accounted for?
5. Don't trust diagnoses of conditions
If you want to find a correlation between a gene G and a trait T, you'd better be sure what T actually is. If it's a whole set of different behaviors, conveniently bundled into a condition T (such as schizophrenia), then you're in trouble, since each of these conditions may have its own causative agent. Many major diseases may be caused by more than one underlying condition, with a different genetic background. So, if you are seeking to find the common thread between people with trait T, you might not find it because there is no common thread!
My guess is that the bulk of the missing heritability is to be found in three sources:
- Epistasis. Humans are makeshift accidents of evolution, and not well-engineered machines where the effects of individual components have been designed to work well in isolation, shielding other components from their effects. Most things in the human body affects most other things, either directly or indirectly. There are, of course, some master switches which do have individual pronounced effects (e.g., giving you lactose tolerance or breast cancer), but these are the exception. Normal variation is due to how well-put together the individual is, and not so much in the individual components.
- Gene-Environment interactions. Just as the effect of genes depends on the joint presence of other genes (epistasis), so it depends on the presence of particular environmental influences. Imagine an allele that shows zero association with a particular trait. Does this mean that it has no influence on that trait? No, since zero association is perfectly compatible with even a huge influence, provided that a positive influence under one type of genomic or environmental background is balanced by a negative influence under another.
- Very low frequency (family) alleles. Natural selection faces a constant battle against the continuing re-emergence of less-than-optimal alleles. Children are almost certainly on average genetically worse than their parents, since parents have survived and reproduced, while children's ability to do so is yet to be tested (*) While human variation is -in part- due to long-lived alleles that have braved the generations, quite a lot of it is due to recent alleles that arose in families, and have not had the time to spread to many bodies. It is these extremely rare family alleles and allele combinations that population studies can't quite capture.
Some related posts on the limits of genome-wide association studies: on intelligence, on height and body mass index, and on CNVs.
(*) Incidentally, this is why the population replacement rate is more than 2 children per woman.
November 05, 2008
Time-dependency of the human mtDNA evolutionary mutation rate
UPDATE (18/11): Some more thoughts on this topic in a newer post [end update]
I had planned to write a post titled: "On the difficulty of archaeological calibration of the mutation rate", for some time. My goal was to follow on my criticism of the proposed explanation for a supposedly lower evolutionary rate, by a criticism of the alleged fact that such a lower rate is proven by archaeological calibration.
So, I was pleasantly surprised to see a new paper which allows me to frame my thoughts in a concrete context. The new paper's purpose is precisely this: to calibrate the evolutionary mutation rate archaeologically.
PREAMBLE
A molecular clock typically works according to this generic equation:
VARIATION = TIME * MUTATION RATE
Some measure of VARIATION is obtained in the present time (e.g. the ρ or π statistics in this paper), and some estimate of the MUTATION RATE is established. This allows us to calculate an estimate of TIME.
How is the MUTATION RATE established? Either by direct measurement, i.e., by looking at relatives and seeing how their genotypes actually differ from each other, or by calibration whereby present-day VARIATION is measured for events with (supposedly) known TIME, leading to an estimate of the MUTATION RATE as VARIATION/TIME.
"KNOWN" TIME?
Two typical examples of calibration go like this:
But, consider more well-established archaeological events like the arrival of the Native Americans which is based on carbon dating and surveys of many sites across the continent. This, apparently gives us a secure T. Or does it?
There are at least two reasons why it does not: demography and selection.
The arrival of Europeans in the new World is perfectly known: it started in 1492. Pre-existing migrants such as the Vikings do not appear to have made a lasting contribution. Yet, if we calculate diversity within European-origin haplogroups in the New World, we will find that they are pretty much as diverse as they are in Europe, Why? Because the migration involved a large number of migrants.
If, a few thousand years from now, after a collapse and rebirth of human civilization, geneticists look at the genes of Americans of that future time, they might conclude that Amerindians and Europeans arrived to the continent at the same time, or even that lineages of the latter (e.g., mtDNA haplogroup U5) preceded those of the former (e.g., mtDNA haplogroup D1).
But, suppose that a limited number of migrants arrive at the archaeologically calibrated time, i.e., a "founder effect", e.g., a single mtDNA D1 "mother" arrived in the New World T years ago.
How do we know that she is the most-recent-common anestor of present-day D1 women from the New World?
We know that she is a common ancestor, but not necessarily the most recent common ancestor (MRCA). Indeed, if selection is at play, then particular lineages overwhelm those of their relatives, and an D1 woman with an advantageous lineage, who lived long after the first D1 woman, may be the real MRCA.
Thus, archaeological calibration is often an illusion: lineages may appear to be older or younger than the calibration time, depending on the population's demography and the effects of selection.
THE NON-EXISTING CONSENSUS
The authors of this study take for granted that there is a discrepancy between the mutation rate created by measurement and calibration (germline vs. evolutionary). Yet, a recent paper paints quite a different picture, finding no difference between the two rates. How do they arrive at such a conclusion? By looking directly at the gene pool of a population in two different points in time (using ancient DNA), and not relying on calibration.
TIME-DEPENDENCY OF THE MUTATION RATE
These criticisms aside, the current paper does have some important implications about the evolutionary rate. Its central idea is that the molecular clock works like this:
VARIATION = TIME * MUTATION RATE(TIME)
i.e., that the MUTATION RATE is itself a function of time. The above equation, like its previous simpler version allows us to estimate TIME from VARIATION. But, it introduces an additional complication. How does the evolutionary mutation rate vary across different time scales?
This, in itself, is a step in the right direction. For example, in human Y-chromosomes a slower evolutionary rate was proposed by Zhivotovsky et al. (2004) (pdf) based on ~1,000 year histories of Bulgarian Gypsies and Polynesians, and a very different rate was proposed by Forster et al. (2000), using a different calibration based on Native American prehistory. Yet, the more widely used Zhivotovsky rate has been used to age 2,700 or 60,000-year-old haplogroups, as if it was equally applicable in both time scales.
The authors of this paper make some interesting comments:
Continuing:
Continuing:
The key word here is small, which is why using such reduced rates for haplogroups that consist of tens of millions of men is nonsense.
Which is pretty much what I've been saying for the last few months:
CONCLUSION
I have expressed my reservations about the difficulty of "archaeological calibration" of the mutation rate. These thoughts pertain to the difficulty of obtaining a valid calibration point due to demography and selection. They also find indirect support from calibration of the mutation rate via ancient DNA.
Nonetheless, even within a calibrationist framework, this paper shows that human mtDNA over the last 5,000 years has accumulated variation at the germline (pedigree) mutation rate, and has extrapolated that in the last 15ky at something close to it -- and definitely not at a much slower rate.
Hopefully, this paper will be extended to rethink the calibration of human Y-chromosome and autosomal mutation rates, and its assumptions may be checked from ancient DNA-based calibration in both humans and other species.
Molecular Biology and Evolution doi: 10.1093/molbev/msn244
Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates
Brenna M. Henn et al.
Abstract
Previous research has established a discrepancy of nearly an order of magnitude between pedigree-based and phylogeny-based (human vs. chimpanzee) estimates of the mitochondrial (mtDNA) control region mutation rate. We characterize the time-dependency of the human mitochondrial hypervariable region one (HVRI) mutation rate by generating fourteen new phylogeny-based mutation rate estimates using within-human comparisons and archaeological dates. Rate estimates based on population events between 15,000 and 50,000 years ago are at least twofold lower than pedigree-based estimates. These within-human estimates are also higher than estimates generated from phylogeny-based human-chimpanzee comparisons. Our new estimates establish a rapid decay in evolutionary mutation rate between approximately 2,500 and 50,000 years ago, and a slow decay from 50,000 to 6 million years ago. We then extend this analysis to the mtDNA coding region. Our within-human coding region mutation rate estimates display a similar, though less rapid, time-dependent decay. We explore the possibility that multiple hits explain the discrepancy between pedigree-based and phylogeny-based mutation rates. We conclude that while nucleotide substitution models incorporating multiple-hits do provide a possible explanation for the discrepancy between pedigree-based and human-chimpanzee mutation rate estimates, they do not explain the rapid decline of within-human rate estimates. We propose that demographic processes such as serial bottlenecks prior to the Holocene could explain the difference between rates estimated before and after 15,000 years ago. Our findings suggest that human mitochondrial DNA estimates of dates of population and phylogenetic events should be adjusted in light of this time-dependency of the mutation rate estimates.
Link
I had planned to write a post titled: "On the difficulty of archaeological calibration of the mutation rate", for some time. My goal was to follow on my criticism of the proposed explanation for a supposedly lower evolutionary rate, by a criticism of the alleged fact that such a lower rate is proven by archaeological calibration.
So, I was pleasantly surprised to see a new paper which allows me to frame my thoughts in a concrete context. The new paper's purpose is precisely this: to calibrate the evolutionary mutation rate archaeologically.
PREAMBLE
A molecular clock typically works according to this generic equation:
VARIATION = TIME * MUTATION RATE
Some measure of VARIATION is obtained in the present time (e.g. the ρ or π statistics in this paper), and some estimate of the MUTATION RATE is established. This allows us to calculate an estimate of TIME.
How is the MUTATION RATE established? Either by direct measurement, i.e., by looking at relatives and seeing how their genotypes actually differ from each other, or by calibration whereby present-day VARIATION is measured for events with (supposedly) known TIME, leading to an estimate of the MUTATION RATE as VARIATION/TIME.
"KNOWN" TIME?
Two typical examples of calibration go like this:
- Humans and Chimps split T millions of years ago. The amount of human-chimp differentiation is D. Therefore, the human-chimp divergence rate was on average D/T over the time period of T years.
- The ancestors of Native Americans arrived T thousands of years ago. Variation within one of their founding lineages (e.g., mtDNA haplogroup D1) is D. Therefore, variation increased by a rate of D/T over the time period of T years.
But, consider more well-established archaeological events like the arrival of the Native Americans which is based on carbon dating and surveys of many sites across the continent. This, apparently gives us a secure T. Or does it?
There are at least two reasons why it does not: demography and selection.
The arrival of Europeans in the new World is perfectly known: it started in 1492. Pre-existing migrants such as the Vikings do not appear to have made a lasting contribution. Yet, if we calculate diversity within European-origin haplogroups in the New World, we will find that they are pretty much as diverse as they are in Europe, Why? Because the migration involved a large number of migrants.
If, a few thousand years from now, after a collapse and rebirth of human civilization, geneticists look at the genes of Americans of that future time, they might conclude that Amerindians and Europeans arrived to the continent at the same time, or even that lineages of the latter (e.g., mtDNA haplogroup U5) preceded those of the former (e.g., mtDNA haplogroup D1).
But, suppose that a limited number of migrants arrive at the archaeologically calibrated time, i.e., a "founder effect", e.g., a single mtDNA D1 "mother" arrived in the New World T years ago.
How do we know that she is the most-recent-common anestor of present-day D1 women from the New World?
We know that she is a common ancestor, but not necessarily the most recent common ancestor (MRCA). Indeed, if selection is at play, then particular lineages overwhelm those of their relatives, and an D1 woman with an advantageous lineage, who lived long after the first D1 woman, may be the real MRCA.
Thus, archaeological calibration is often an illusion: lineages may appear to be older or younger than the calibration time, depending on the population's demography and the effects of selection.
THE NON-EXISTING CONSENSUS
The authors of this study take for granted that there is a discrepancy between the mutation rate created by measurement and calibration (germline vs. evolutionary). Yet, a recent paper paints quite a different picture, finding no difference between the two rates. How do they arrive at such a conclusion? By looking directly at the gene pool of a population in two different points in time (using ancient DNA), and not relying on calibration.
TIME-DEPENDENCY OF THE MUTATION RATE
These criticisms aside, the current paper does have some important implications about the evolutionary rate. Its central idea is that the molecular clock works like this:
VARIATION = TIME * MUTATION RATE(TIME)
i.e., that the MUTATION RATE is itself a function of time. The above equation, like its previous simpler version allows us to estimate TIME from VARIATION. But, it introduces an additional complication. How does the evolutionary mutation rate vary across different time scales?
This, in itself, is a step in the right direction. For example, in human Y-chromosomes a slower evolutionary rate was proposed by Zhivotovsky et al. (2004) (pdf) based on ~1,000 year histories of Bulgarian Gypsies and Polynesians, and a very different rate was proposed by Forster et al. (2000), using a different calibration based on Native American prehistory. Yet, the more widely used Zhivotovsky rate has been used to age 2,700 or 60,000-year-old haplogroups, as if it was equally applicable in both time scales.
The authors of this paper make some interesting comments:
Genealogy-based rate estimates between 2,500-5,000ya are indistinguishable from pedigree-based mutation rate estimate (tables 1-2).So, for events of the recent past, to at least the Bronze Age, "pedigree" and "evolutionary" rates are indistinguishable. Lineages that appear to be of Bronze Age origin based on the pedigree rate, are indeed that old, and not Neolithic or Paleolithic as might be predicted by use of a slower "evolutionary" rate.
Continuing:
The time period between 5,000ya and ~15,000ya represents both a break in our dataset and a sudden decline in estimated mutation rate (fig. 2). Estimates for the intermediate period roughly 15,000ya are about 40% lower than estimates calibrated on arrival dates less than 5,000yaThis is a break in their dataset because, well, they don't have any calibration points between 5-15ky. Thus, their estimate is nothing more than an extrapolation based on calibration points younger than 5ky or older than 15ky. But still, their estimates for even 15ky (which upper bounds all the Neolithic and Mesolithic for humans) are only 40% lower than using pedigree rates. Thus, even if we accept this extrapolation, ages between 5 and 15ky using the pedigree rate may be somewhat underestimated, but certainly not by a huge factor.
Continuing:
Using simulation, Zhivotovsky, Underhill and Feldman (2006) showed that microsatellite mutation rates estimated from small populations (haplogroups) undergoing serial bottlenecks are indeed reduced compared to pedigree-based rates.
The key word here is small, which is why using such reduced rates for haplogroups that consist of tens of millions of men is nonsense.
In simple English, they propose that the evolutionary mutation rate for large Neolithic populations was close to the pedigree rate, while for the smaller pre-Neolithic hunter-gatherer groups it was much lower.
The striking difference between our mutation rate estimates from before and after 20,000 years ago suggests that demographic history may play an important role. Prior to the Last Glacial Maximum lasting between 22,000-15,000ya, human populations were characterized by small, mobile hunter-gatherer groups that may have been frequently subject to fluctuations in population size. Following the LGM, humans experienced far fewer climatic swings (Mithen 2004). Particularly after the Younger Dryas cycle, agriculture facilitated dramatic population growth and serial bottlenecks were unlikely to substantially reduce the diversity of such large populations. A dramatic increase in population size during the Neolithic period is supported by mtDNA genomes from African, southeastern Asian, and European populations (Gignoux C, Henn B, unpublished data). We propose that a population history consisting of serial bottlenecks followed by recent population growth currently provides the most compelling explanation for the time-dependency of human hypervariable and coding region mtDNA mutation rate estimates.
Which is pretty much what I've been saying for the last few months:
But, if you read Zhivotovsky, Underhill and Feldman (2006) or my two previous posts on the subject, you will realize that the effective rate depends on population history; that the 0.00069 rate is derived for constant-sized populations where haplogroups never grow to large numbers.or:
Of course, if one studies numerically small populations, it is possible that a slower effective rate may be desired. My concern is with the large human populations (e.g. Greeks or Indians) where real haplogroup sizes exceed greatly those produced by simulations with reproductive equality.or:
Z.U.F. have also proposed two additional demographic scenaria under which a higher effective mutation rate would be observed:Let's hope that -if nothing else- this paper will be the beginning of the end for the indiscriminate use of "evolutionary rates" across different time spans and marker systems. I am not counting on this happening any time soon, given the substantial intellectual inertia of the field.Both factors seem reasonable for post-Holocene human populations. It is well known that -whatever temporary setbacks there were- mankind has overall experienced a substantial population growth in recent millennia. Thus, an expanding population seems like a fair assumption.
- A sudden jump in the size of the haplogroup after it appears
- An expanding population (m>1)
CONCLUSION
I have expressed my reservations about the difficulty of "archaeological calibration" of the mutation rate. These thoughts pertain to the difficulty of obtaining a valid calibration point due to demography and selection. They also find indirect support from calibration of the mutation rate via ancient DNA.
Nonetheless, even within a calibrationist framework, this paper shows that human mtDNA over the last 5,000 years has accumulated variation at the germline (pedigree) mutation rate, and has extrapolated that in the last 15ky at something close to it -- and definitely not at a much slower rate.
Hopefully, this paper will be extended to rethink the calibration of human Y-chromosome and autosomal mutation rates, and its assumptions may be checked from ancient DNA-based calibration in both humans and other species.
Molecular Biology and Evolution doi: 10.1093/molbev/msn244
Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates
Brenna M. Henn et al.
Abstract
Previous research has established a discrepancy of nearly an order of magnitude between pedigree-based and phylogeny-based (human vs. chimpanzee) estimates of the mitochondrial (mtDNA) control region mutation rate. We characterize the time-dependency of the human mitochondrial hypervariable region one (HVRI) mutation rate by generating fourteen new phylogeny-based mutation rate estimates using within-human comparisons and archaeological dates. Rate estimates based on population events between 15,000 and 50,000 years ago are at least twofold lower than pedigree-based estimates. These within-human estimates are also higher than estimates generated from phylogeny-based human-chimpanzee comparisons. Our new estimates establish a rapid decay in evolutionary mutation rate between approximately 2,500 and 50,000 years ago, and a slow decay from 50,000 to 6 million years ago. We then extend this analysis to the mtDNA coding region. Our within-human coding region mutation rate estimates display a similar, though less rapid, time-dependent decay. We explore the possibility that multiple hits explain the discrepancy between pedigree-based and phylogeny-based mutation rates. We conclude that while nucleotide substitution models incorporating multiple-hits do provide a possible explanation for the discrepancy between pedigree-based and human-chimpanzee mutation rate estimates, they do not explain the rapid decline of within-human rate estimates. We propose that demographic processes such as serial bottlenecks prior to the Holocene could explain the difference between rates estimated before and after 15,000 years ago. Our findings suggest that human mitochondrial DNA estimates of dates of population and phylogenetic events should be adjusted in light of this time-dependency of the mutation rate estimates.
Link
November 02, 2008
Maternal inheritance and male reproductive fitness
Humans get roughly half their genes from each parent, but mothers affect their offspring in additional ways. First, there is mtDNA which is inherited only from one's mother. Second, there is epigenetic inheritance via mothers' eggs, which covers all their non-genetic qualities of these cells which grow up (post-fertilization) to become humans.
If a maternally inherited trait reduces the genetic fitness of a woman, then it will be under negative selection, and will be weeded out. If, on the other hand, it reduces the genetic fitness of a man, then it will not be affected at all: this reduction in fitness has no evolutionary effect since maternally inherited traits (e.g., mtDNA) are doomed in male bodies anyway.
Not surprisingly, such traits have been implicated in male sperm quality conditions, with e.g., specific haplogroups leading to reduced sperm count or mobility.
Sexual selection theory suggests that humans pick their mates because of their "good genes" (see other recent post). But this raises this issue: if males with good genes are selected for in each generation, then how come is a great reproductive skew maintained in the human species: why do some men produce many offspring while many produce none or a few? And, why do women often "cheat" on their mates, having children with others than their official mates.
Maternal inheritance explains this paradox: male reproductive variation due to the Y-chromosome or the autosomes can be shaped by evolution to produce males with good (well-adapted) genes, but maternally inherited factors cannot.
UPDATE: Interestingly, this may solve the paradox of non-inheritance of male attractiveness. While sexy parents have sexy daughters, apparently they don't tend to have especially attractive sons. This may be due to male-expressed maternally inherited traits. Such traits don't make their mothers' attractive (they are male expressed), and they are not inherited from their fathers.
Genetica. 2008 Sep;134(1):45-54.
Maternal inheritance, epigenetics and the evolution of polyandry
Zeh JA, Zeh DW.
Abstract
Growing evidence indicates that females actively engage in polyandry either to avoid genetic incompatibility or to bias paternity in favor of genetically superior males. Despite empirical support for the intrinsic male quality hypothesis, the maintenance of variation in male fitness remains a conundrum for traditional "good genes" models of sexual selection. Here, we discuss two mechanisms of non-Mendelian inheritance, maternal inheritance of mitochondria and epigenetic regulation of gene expression, which may explain the persistence of variation in male fitness traits important in post-copulatory sexual selection. The inability of males to transmit mitochondria precludes any direct evolutionary response to selection on mitochondrial mutations that reduce or enhance male fitness. Consequently, mitochondrial-based variation in sperm traits is likely to persist, even in the face of intense sperm competition. Indeed, mitochondrial nucleotide substitutions, deletions and insertions are now known to be a primary cause of low sperm count and poor sperm motility in humans. Paradoxically, in the field of sexual selection, female-limited response to selection has been largely overlooked. Similarly, the contribution of epigenetics (e.g., DNA methylation, histone modifications and non-coding RNAs) to heritable variation in male fitness has received little attention from evolutionary theorists. Unlike DNA sequence based variation, epigenetic variation can be strongly influenced by environmental and stochastic effects experienced during the lifetime of an individual. Remarkably, in some cases, acquired epigenetic changes can be stably transmitted to offspring. A recent study indicates that sperm exhibit particularly high levels of epigenetic variation both within and between individuals. We suggest that such epigenetic variation may have important implications for post-copulatory sexual selection and may account for recent findings linking sperm competitive ability to offspring fitness.
Link
If a maternally inherited trait reduces the genetic fitness of a woman, then it will be under negative selection, and will be weeded out. If, on the other hand, it reduces the genetic fitness of a man, then it will not be affected at all: this reduction in fitness has no evolutionary effect since maternally inherited traits (e.g., mtDNA) are doomed in male bodies anyway.
Not surprisingly, such traits have been implicated in male sperm quality conditions, with e.g., specific haplogroups leading to reduced sperm count or mobility.
Sexual selection theory suggests that humans pick their mates because of their "good genes" (see other recent post). But this raises this issue: if males with good genes are selected for in each generation, then how come is a great reproductive skew maintained in the human species: why do some men produce many offspring while many produce none or a few? And, why do women often "cheat" on their mates, having children with others than their official mates.
Maternal inheritance explains this paradox: male reproductive variation due to the Y-chromosome or the autosomes can be shaped by evolution to produce males with good (well-adapted) genes, but maternally inherited factors cannot.
UPDATE: Interestingly, this may solve the paradox of non-inheritance of male attractiveness. While sexy parents have sexy daughters, apparently they don't tend to have especially attractive sons. This may be due to male-expressed maternally inherited traits. Such traits don't make their mothers' attractive (they are male expressed), and they are not inherited from their fathers.
Genetica. 2008 Sep;134(1):45-54.
Maternal inheritance, epigenetics and the evolution of polyandry
Zeh JA, Zeh DW.
Abstract
Growing evidence indicates that females actively engage in polyandry either to avoid genetic incompatibility or to bias paternity in favor of genetically superior males. Despite empirical support for the intrinsic male quality hypothesis, the maintenance of variation in male fitness remains a conundrum for traditional "good genes" models of sexual selection. Here, we discuss two mechanisms of non-Mendelian inheritance, maternal inheritance of mitochondria and epigenetic regulation of gene expression, which may explain the persistence of variation in male fitness traits important in post-copulatory sexual selection. The inability of males to transmit mitochondria precludes any direct evolutionary response to selection on mitochondrial mutations that reduce or enhance male fitness. Consequently, mitochondrial-based variation in sperm traits is likely to persist, even in the face of intense sperm competition. Indeed, mitochondrial nucleotide substitutions, deletions and insertions are now known to be a primary cause of low sperm count and poor sperm motility in humans. Paradoxically, in the field of sexual selection, female-limited response to selection has been largely overlooked. Similarly, the contribution of epigenetics (e.g., DNA methylation, histone modifications and non-coding RNAs) to heritable variation in male fitness has received little attention from evolutionary theorists. Unlike DNA sequence based variation, epigenetic variation can be strongly influenced by environmental and stochastic effects experienced during the lifetime of an individual. Remarkably, in some cases, acquired epigenetic changes can be stably transmitted to offspring. A recent study indicates that sperm exhibit particularly high levels of epigenetic variation both within and between individuals. We suggest that such epigenetic variation may have important implications for post-copulatory sexual selection and may account for recent findings linking sperm competitive ability to offspring fitness.
Link
Sexy parents produce sexy daughters (but not sons)
A very interesting new paper in Animal Behaviour regarding the inheritance of masculinity/famininity and attractiveness. On the left are composites of 10 attractive parents and their daughters, and on the right composites of 10 unattractive parents and their daughters.Not surprisingly, the attractive female looks similar to another facial composite in a recent study on facial correlates of sociosexuality by authors from the same institution (University of St. Andrews in the UK).
The difference between Fisherian runaway selection and "good genes" theory -mentioned below- is that in the former, a "sexy" trait is selected even though it has no adaptive value (such as the peacock's tail), while in the latter the latter the "sexy" trait is that which signifies good genetic qualities (e.g. health).
From the paper:
Our findings are supportive of both Fisherian processes and good genes theory. Both parents contributed to the attractiveness and femininity of daughters. We found that daughter's attractiveness was predicted independently by father's attractiveness and mother's femininity (and therefore, by default, mother's attractiveness). Fisherian selection processes would suggest that men have evolved preferences for sexually dimorphic facial characteristics in opposite-sex partners, and through human evolution these preferences have increased the frequency of feminine facial characteristics such as a slender chin, full lips and large eyes in women. Good genes theory predicts the same finding, although it suggests that feminine facial characteristics must by definition signal good quality, including possible cues to immunocompetence, fertility, youthfulness, health and perhaps even maternal tendenciesUPDATE : For a possible solution to this paradox, see next post.
...
We are perplexed as to why we did not find any evidence for the inheritance of attractiveness in males, through either the female or male parent. Attractiveness, by its own definition, should be sexy, and while we found evidence for sexy parents–sexy daughters, we did not find the parallel in male offspring. While masculine dads produced masculine sons, in this study, sexy parents did not produce sexy sons.
Animal Behaviour doi: 10.1016/j.anbehav.2008.07.031
Sexy sons and sexy daughters: the influence of parents' facial characteristics on offspring
R. Elisabeth Cornwell, and David I. Perrett
Abstract
Choosing a mate to maximize fitness underlies all sexual selection theories. Key to understanding mate choice is the inheritance of particular traits. Using family photos, we evaluated the predictions made by sexual selection theories for human mate choice concerning the inheritance of facial characteristics and assortment in facial appearance of parents. We found that both fathers' and mothers' attractiveness predicted the facial attractiveness of daughters: ‘sexy daughters’. Fathers and sons were related to each other in facial masculinity but not attractiveness, providing only partial evidence for ‘sexy sons’. Mothers and sons did not relate in masculinity–femininity; neither did fathers and daughters. Parents were similar in attractiveness but masculine men were not partnered to feminine women. Our findings support some predictions of Fisherian selection processes and ‘good genes’ theory but are less consistent with ‘correlated response theory’ and the immunocompetence handicap principle.
Link
23andme's advanced global similarity tool
UPDATE: I am told that this tool is currently in alpha version, so it's not clear when it will be fully ready for 23andme customers. As per my comments below, I think this is a great initiative to tie individual customers' genetic data to the many new genetic studies showing genomic-geographic correlations. I am sure that 23andme's blog, the Spittoon, will cover this when it is ready for public release, including any features that I may have overlooked. I will be following this story closely. [end update]
23andme has added a new advanced global similarity tool to their website (you need to register in order to play with it). This tool places a customer, as well as other customers he is "connected" with on the map of the first two principal components like the ones recently published in several papers.
The tools allows one to look at the PC map at the global, continental, or subcontinental level.
This is quite useful, and a right step in the direction I pointed out earlier. However, there are some points of criticism.
23andme has added a new advanced global similarity tool to their website (you need to register in order to play with it). This tool places a customer, as well as other customers he is "connected" with on the map of the first two principal components like the ones recently published in several papers.
The tools allows one to look at the PC map at the global, continental, or subcontinental level.
This is quite useful, and a right step in the direction I pointed out earlier. However, there are some points of criticism.
- The axes are labeled North/South Migration and East/West Migration. While the pattern in the first two principal components does correspond roughly with longitude and latitude, it is erroneous to label these principal components as "North/South" and "East/West". It is even more erroneous to label them as "Migration", since a geographical cline is not necessarily produced by a migration event.
- The "Take a Tour" feature presents a simplistic and misleading account of human prehistory in terms of "migrations". This account is a simple branching pattern, e.g., Africa -> Near East Europe, or Africa -> Near East -> Central Asia -> East Asia. The observed pattern did not emerge in this manner. For example, Central Asian people such as the Uyghur are intermediate between Western Eurasians (Caucasoids) and Eastern Eurasians (Mongoloids) because of a later admixture event; they can't be thought of as "ancestors" of the East Eurasians.
- Partitioning human variation into this hierarchical set of groups is not the best way to satisfy customers' needs. For example, a Hispanic person may wish to see himself on a PC map which includes "Southern European" and "Native American" groups, an African American person may wish to see himself on a PC map which includes "Northern European" and "West African" groups, an Ethiopian, on a Sub-Saharan/Near Eastern map, while a European Jew on a European/Near Eastern map. Of course, there is a combinatorial number of possible combinations, but there is no reason why some of the more common ones (customer feedback may play a role here) many not be supported.
- Why should this tool be limited to the first two principal components? Of course, additional components do not have such a strong geographical correspondence, but they -nonetheless- will separate populations in different ways, and allow individuals to place themselves more fully in context.
- The tool could offer much more information. On mouse hover over an individual, a small label identifying it (e.g. origin and HGDP code), and listing its PC coordinates could appear. This is especially useful for power users. A pretty uncluttered picture is no substitute for as much information as possible.
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