Sunday, March 26, 2017

There Was Intense Selection For Vivax Malaria Protective Genes In Africa 40kya

The Secret History Of Mankind's Struggle With Malaria In Africa

Now, vivax malaria is the second most common variety of malaria discussed in the article below (and is the most common type outside of Africa). According to Wikipedia first discussing malaria generally and then the two most common types of it:
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator. This includes much of Sub-Saharan Africa, Asia, and Latin America. In 2015, there were 214 million cases of malaria worldwide resulting in an estimated 438,000 deaths, 90% of which occurred in Africa. . . .  
Although P. falciparum traditionally accounts for the majority of deaths, recent evidence suggests that P. vivax malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of P. falciparum infection.
But, ca. 40,000 years ago in parts of Africa (not those less tropical areas where the Khoi-san bushmen lived), a genetic mutation protective against vivax malaria "conferred a selective advantage of about 4.3%, leading to effective fixation in about 8,000 years." 

A parallel story mostly involving P. falciparum is told in the genetics of similarly intense selective pressure on genes including sickle cell trait, thalassaemia traits, and glucose-6-phosphate dehydrogenase deficiency. The combined lethality of all kinds of malaria was thus almost certainly considerably greater than indicated by the selective advantage against one kind of malaria conferred by this gene (which related to what are called "Duffy antigens") alone.

Duffy antigen genes also have multiple applications in population genetics.

A Hint About Intra-African Human History?

Anatomically modern humans have been present in African from ca. 150,000 to 250,000 years ago and archaic hominins have been present in Africa for millions of years. Moreover, it is unlikely that malaria vivax was limited to modern humans. Many forms of malaria can also affect other great apes beside humans, and archaic hominins would have been very similar to modern humans in terms of traits that would have made them vulnerable to, or resistant to, modern humans.

So, the most notable aspect of the protective Duffy antigen genes in humans is not that they are present, but that they arose so recently and only after the founding population of non-Africans left the continent.

In particular, the TMRCA date for the Duffy antigen gene that has reached fixation in tropical Africans isn't that far from the 60,000 years before present TMRCA date for African Pygmies, an African population with one of the most basal divisions from other modern humans in Africa (together with the Khoisan people who are somewhat more basal) that lives mostly in the rainforests of the vast Congo River basin jungle of tropical Africa.

So, while it could be that modest population sizes meant that it simply took a long time for a protective Duffy antigen mutation to occur, it is also quite plausible that the timing is an indication that modern humans in Africa did not live in tropical areas heavily afflicted with malaria mosquitos until ca. 40,000 years ago (plus however long it took for a mutation to emerge once they started live there).

This, combined with knowledge about which parts of Africa were historically deserts or rain forests could shed a lot of light in the question of the historical range of modern humans and their archaic hominin ancestors in the time frame from their earliest evolution to ca. 40,000 years ago, ruling out much of West Africa and Central Africa from that range.

The Article

As explained by a new article revealing this fact:
The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. 
Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. 
We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34–49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011–0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48–65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause. 
Infectious diseases have undoubtedly played an important role in ancient and modern human history. Yet, there are relatively few regions of the genome involved in resistance to pathogens that show a strong selection signal in current genome-wide searches for this kind of signal. We revisit the evolutionary history of a gene associated with resistance to the most common malaria-causing parasite, Plasmodium vivax, and show that it is one of regions of the human genome that has been under strongest selective pressure in our evolutionary history (selection coefficient: 4.3%). Our results are consistent with a complex evolutionary history of the locus involving selection on a mutation that was at a very low frequency in the ancestral African population (standing variation) and subsequent differentiation between European, Asian and African populations.
Kimberly F. McManus, et al., "Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans" PLOS Genetics (March 10, 2017).


This suggests that vivax malaria was very lethal (or at least reproduction preventing) in tropical Africa at the time, killing 4.3% of the entire unprotected population each generation (and a higher percentage of unprotected people who were infected, as not every single person in each generation would have been infected).

About 6% of the population in malaria vulnerable areas of the world are infected with malaria each year also it is predominantly lethal in children aged five and younger who account for 70% of deaths from malaria. Infection rates are much higher in tropical Africa where about 90% of malaria deaths occur.

Infection rates were much higher, about 15%-30% each year as recently as the early 20th century in Africa and sometimes more; there was a dramatic drop in malaria from 11.4% to 0.4% from 1940 to 1942. It is this pervasive infection rate that makes it particularly deadly. "A 2002 report stated that malaria kills 2.7 million people each year, more than 75 percent of them African children under the age of five. "

Thus, vivax malaria would have been more lethal than

* the Spanish flu of 1918
* untreated whooping cough
* measles in modern developing countries 
* lassa fever
* mumps
* treated Dengue fever
* treated tularemia
* diphtheria
* botulism
* perhaps even untreated typhoid fever or SARS (if the infection rate wasn't that high).

Of course, this lethality estimate assumes that the mutation is 100% protective, which it probably isn't. So, due to its probable less than 100% infection rate and its probable less than 100% protectiveness, the actual lethality of vivax malaria in this time period was probably significantly greater than 4.3% per generation of unprotected people.

Modern malaria (all kinds) kills only about 1 in 300 of people infected with it - this ancient strain that lasted 8,000 years would have been more than 14 times more lethal than malaria is today.

It is also possible that the selective advantage may have had a significant fertility component as opposed to purely a lethality effect since in modern populations: "Malaria in pregnant women is an important cause of stillbirths, infant mortality, abortion [i.e. miscarriage] and low birth weight, particularly in P. falciparum infection, but also with P. vivax." If malaria infection rates were very high (as seems likely), these fertility effects could have given rise to a large share of the selective fitness benefit even if the lethality of an infection was only modest.

New World History - Disease As A Factor In The Slave Trade

This evolutionary history shaped the early days of the Americas by contributing to the history of slavery in the Americas. As a result of genetic adaptations to tropical diseases including vivax malaria, the mortality of African working on plantations in the American South, the Caribbean, and South America was lower than that of Europeans.

This lower mortality rate, in turn, is one of the factors that caused these parts of the America to develop an agricultural economy based upon African slave labor rather than European colonists as the Northern United States and Canada and some other parts of South America did.

Basque Genetics

Duffy antigen genes are one area among many in which Basque population genetics are distinctive (although some assumptions of this 2005 article are now outdated).
The Basques live at the western end of the Pyrenees along the Atlantic Ocean and are thought to represent the descendants of a pre-Neolithic people. They demonstrate marked specificities regarding language and genetics among the European populations. We review the published data on the population genetics and Mendelian disorders of the Basques. 
An atypical distribution in some blood group polymorphisms (ABO, Rhesus, and Duffy) was first found in this population. Subsequently, additional characteristics have been described with regard to proteins (enzymes and immunoglobulins) and the HLA system. The advent of molecular biology methods in the 1990s allowed further insights into Basque population genetics based mainly on Y-chromosome and mitochondrial DNA. In addition, the Basques demonstrate peculiarities regarding the distribution of various inherited diseases (i.e., unusual frequencies or founding effects). Taken together, these data support the idea of an ancient and still relatively unmixed population subjected to genetic drift.
Frederic Bauduer, J. Feingold, and Didier Lacombe, "The Basques: Review of Population Genetics and Mendelian Disorders" 77(5) Human Biology 619-637 (October 2005) (closed access).

Saturday, March 25, 2017

Thursday, March 23, 2017

Mediterranean Farmers Took Local Mesolithic Era Migration Wives

Much of the modern mtDNA of Europe (with exception of mtDNA U and perhaps mtDNA V) is derived from mtDNA clades in West Asia and Southwest Asia. The latest study focused on clades of mtDNA J and mtDNA T in modern Europeans, dating their formative periods via mutation rate dating and phylogeny.

In Central Europe and Iberia, these Near Eastern mtDNA clades arrived with more or less gender balanced first farmer families in the Neolithic revolution. 

But, in central and eastern Mediterranean Europe (presumably Greece, the Balkans, Italy and Southern France), these mtDNA clades arrived in the Mesolithic era, after the Younger Dryas ice age, but before farming was introduced. Local women were then integrated into the farming societies that arrived later in the Mediterranean Neolithic revolution (mostly notably the Cardial Pottery Neolithic).
Important gaps remain in our understanding of the spread of farming into Europe, due partly to apparent contradictions between studies of contemporary genetic variation and ancient DNA. 
It seems clear that farming was introduced into central, northern, and eastern Europe from the south by pioneer colonization. It is often argued that these dispersals originated in the Near East, where the potential source genetic pool resembles that of the early European farmers, but clear ancient DNA evidence from Mediterranean Europe is lacking, and there are suggestions that Mediterranean Europe may have resembled the Near East more than the rest of Europe in the Mesolithic. 
Here, we test this proposal by dating mitogenome founder lineages from the Near East in different regions of Europe. We find that whereas the lineages date mainly to the Neolithic in central Europe and Iberia, they largely date to the Late Glacial period in central/eastern Mediterranean Europe. This supports a scenario in which the genetic pool of Mediterranean Europe was partly a result of Late Glacial expansions from a Near Eastern refuge, and that this formed an important source pool for subsequent Neolithic expansions into the rest of Europe.
Joana B. Pereira. et al., "Reconciling evidence from ancient and contemporary genomes: a major source for the European Neolithic within Mediterranean Europe" Proceedings of the Royal Society B (Biology) (March 22, 2017).

Further discussion of the body text of this paper can be found at Bernard's blog (in French).

The Limits Of Consumer Genomic Ancestry Reports

Razib has a nice discussion of the limitations of ancestry assignment methods in consumer genomic products like 23andMe. He makes a couple of key points:

* South Asia has ten times as much intra-regional variation as Northern Europe, but genomics companies currently make little effort to disaggregate this variation outside Europe.

* Consumer genomic companies are in a bind, because the genomic structure of Europe doesn't track the modern national boundaries well. 

Some of the genomic structure of Europe is more clear at a sub-national region level that may cross national boundaries, and some of it is related to events too deep in prehistory to to well known to the general public (e.g. the hunter-gather, first wave Neolithic, and early Bronze Age population shifts plus some minor or only locally significant matters like admixture arising during European colonial empire periods, and major population disruptions in Austria-Hungary). But, without a lot of context, those distinctions don't make much sense to typical personal genomics company customers.

Still No Evidence Of SUSY

Supersymmetry (i.e. SUSY) is not supported by any experimental evidence that distinguishes it from the Standard Model, and the exclusions are far above the weak scale where it was expected to manifest itself. 
This week results are being presented by the LHC experiments at the Moriond (twitter here) and Aspen conferences. While these so far have not been getting much publicity from CERN or in the media, they are quite significant, as first results from an analysis of the full dataset from the 2015+2016 run at 13 TeV, This is nearly the design energy (14 TeV) and a significant amount of data (36 inverse fb/experiment). The target for this year’s run (physics to start in June) is another 45 inverse fb and we’ll not start to hear about results from that until a year or so from now. For 14 TeV and significantly larger amounts of data, the wait will be until 2021 or so. 
The results on searches for supersymmetry reported this week have all been negative, further pushing up the limits on possible masses of conjectured superparticles. Typical limits on gluino masses are now about 2.0 TeV (see here for the latest), up from about 1.8 TeV last summer (see here). ATLAS results are being posted here, and I believe CMS results will appear here.
From here.

In other news from these conferences in progress, there are no newly announced Higgs boson mass or width results, and the experimentally measured fit of the observed Higgs boson couplings to those predicted by the Standard Model remains very tight (comfortably within one standard deviation of the expected value overall).

No significant BSM physics of any kind has been observed definitively at the LHC, although a handful of moderate significance anomalies have been noted that might or might not amount to anything. None of the anomalies are easy and obvious fits to popular BSM theories akin to SUSY.

Monday, March 20, 2017

Another Introgressing Archaic Hominin Species?

Genetic Evidence of Archaic Introgression

Outside Africa

Somehow I missed a notable conclusion in a paper in Nature Genetics this summer on the genetic origins of the Andamanese people, and a related controversy over it.

This paper shows signs of a non-Neanderthal, non-Denisovan archaic hominin species 1-3% admixture (more if more recently diverged, less if less recently diverged) with a species diverged by about 400,000 years +100,000/-200,000 years from modern humans.[1] While this conclusion has certainly not reached a consensus level based upon this single paper, it is a very notable development. This would mean there were three separate archaic species that introgressed into modern humans outside Africa. The archaic species divergence estimated in the Andamanese study seems too recent to be a Homo Erectuswhich should have diverged ca. 1,900,000 years ago when it left Africa, making Homo erectus too old a source for the archaic admixture that was reportedly observed. Another group of prominent researchers, however, was not able to replicate this result, published a refutation within a week, and thinks that it Andamanese paper is erroneous on this point.[2]

UPDATE March 21, 2017:

An April 30, 2014 pre-print at arXiv that I didn't mention thickens the plot (thanks to Ryan in the comment for pointing it out) reveals contributions from two more archaic hominin species to Eurasian genomes that diverged 859,000 and 3,464,000 years ago, both of which belong to common ancestors of modern humans and Neanderthals.[19] There is no indication, however, that the pre-print was ever published, so it may have gotten bogged down by hurdles or substantially revised over the course of the peer review process. The fact that only one of the many co-authors (Li Jin) has many publications in this area could also explain the lack of publication.


In Africa

In addition there were probably probably one to four archaic species that introgressed into modern humans in Africa but not into modern humans outside Africa.[3][4][5][6] There is also the question of what to make of an extremely old African Y-DNA lineage, A00, which could just be an old modern human or proto-modern human lineage, or could be introgressed from an archaic hominin species.[7]

Matching Genetic Signs Of Introgression To Skeletal Remains

The alleged new introgressing species in South/Southeast Asia and in Africa are statistical ghosts derived from modern human genomes.

Denisovan admixture is associated with only by a few teeth and perhaps a knuckle in addition to a strong genetic signal in a few populations, although possibly a very weak signal in other Asian population.[8][9][10]

Only Neanderthals are represented by ample quantities of bones that have been tested for DNA.[11] Neanderthal introgression was found to have been very recent in an individual from 40,000 years ago in Romania whose ancient DNA was tested.[12] Introgression into Altai Neanderthals from modern humans suggests an introgression event ca. 100,000 years ago, predating the common ancestor of all modern humans outside Africa today and suggesting a two wave migration model for modern humans in which the first wave mostly failed.[13] Some African populations have some Neanderthal admixture due to Eurasian back migration.[14]

UPDATE March 23, 2017:

There were probably at least three distinct waves of Neanderthal admixture, in addition to one wave of Denisovan admixture.[20]


And, while not precisely on point, modern human DNA from an individual who died 40,000 years ago in China has been extracted, which is distinctive East Eurasian rather than West Eurasian, and had modern levels of archaic hominin DNA, suggesting that little or no archaic admixture has taken place in East Asia since then.[15]

We also have bones from Homo floresiensis (a.k.a. hobbits) on the island of Flores, and bones from some archaic looking hominins in China not assigned to a species[16], but similar in brain capacity to modern humans and Neanderthals. We have no genetic information from either, but the former, due to its strategic location at the starting point of high levels of Denisovan DNA, and the latter, due to its evolutionary position and geographic location midway between the Altai and Flores, are both prime candidates for Denisovans.

We also have bones classified as Homo heidelbergensis (a.k.a. Homo rhodesiensis) that lived in Africa, Europe and western Asia between 600,000 and 200,000 years ago," which are both about right in terms of age to be an archaic species admixing with modern humans (somewhere, at least). And, we do have ancient DNA from H. heidelbergensis, which presents a complicated story. The mtDNA looked Denisovan,[17] but the nuclear DNA looked significantly more Neanderthal than Denisovan.[18] This "suggests the Neanderthal-Denisovan split happened before 430,000 years ago" (the date of the specimens from which the samples in Spain were taken). This fits with the notion that H. heidelbergensis is a parent clade to the Neanderthals and that Neanderthals and Denisovans are fairly closely related to each other (compared to modern humans and either Neanderthals or Denisovans). Homo heidelbergensis, or an immediate predecessor in Africa (or perhaps a slightly more remote predecessor like Homo ergaster), could also have been an ancestor (at least partially) of modern humans.

Friday, March 17, 2017

Is Poverty Point, Louisiana Evidence Of Complex Social Organization In Hunter-Gathers?

A short partially animated video by the maker of PhD Comics makes the case that Poverty Point, Louisiana is evidence of a far more sophisticated social organization in hunter-gatherers from 1200 BCE than is commonly assumed. 

Given the surprising short timeline of construction of the largest earth mound there (60-90 days which would have taken 1000 laborers plus supporters), I'm inclined to think that, like the pre-Neolithic temples of the Fertile Crescent like Göbekli Tepe, this may have been a periodic meet-up event of an extended clan of tribes a bit like a modern Olympics or extended family reunion. And, while individual mounds may have been built in one go, the entire cluster of mounds may have been built over the course of multiple generations taking centuries. The Wikipedia account of the Anatolian site below is strikingly similar to the one in the video about Poverty Point:
While the site formally belongs to the earliest Neolithic (PPNA), up to now no traces of domesticated plants or animals have been found. The inhabitants are assumed to have been hunters and gatherers who nevertheless lived in villages for at least part of the year. So far, very little evidence for residential use has been found. Through the radiocarbon method, the end of Layer III can be fixed at about 9000 BCE (see above) but it is believed that the elevated location may have functioned as a spiritual center by 11,000 BCE or even earlier, essentially at the very end of the Pleistocene
The surviving structures, then, not only predate pottery, metallurgy, and the invention of writing or the wheel, they were built before the so-called Neolithic Revolution, i.e., the beginning of agriculture and animal husbandry around 9000 BCE. But the construction of Göbekli Tepe implies organization of an advanced order not hitherto associated with Paleolithic, PPNA, or PPNB societies. 
Archaeologists estimate that up to 500 persons were required to extract the heavy pillars from local quarries and move them 100–500 meters (330–1,640 ft) to the site. The pillars weigh 10–20 metric tons (10–20 long tons; 11–22 short tons), with one still in the quarry weighing 50 tons. It has been suggested that an elite class of religious leaders supervised the work and later controlled whatever ceremonies took place. If so, this would be the oldest known evidence for a priestly caste—much earlier than such social distinctions developed elsewhere in the Near East.
Another possibility, but not really consistent with the lack of evidence of settlement and short time frame of construction locally, at least, would have been a somewhat sedentary lifestyle supported by fishing and proto-farming. But, fishing and proto-farming in the Mississippi Delta era could still have given rise to a larger community population that was relatively localized which would make mobilization of a community to build this monument more feasible. Indeed, it may have even been a Chalcolithic technology civilization. According to articles in Science which I summarized in a 2012 post at this site:
A little more than a thousand years later (flourishing 1600 BCE to 1000 BCE), however, a civilization that appears to be derived from this first wave of mound builders appears at Poverty Point, which is within a day's walk of the earlier sites in Louisiana. This urban center is much larger in scale, perhaps comparable to a medium sized archaic era Greek city state, and shows clear signs of a trade network that extends as far as Milwaukee, Wisconsin in the North and the Ozarks in the West. It used copper and engaged in fine stoneworking. Its trade network may have even extended farther still. The way that its structures are aligned with solstices and equinoxes, its burial practices, its pottery, and the arrangement of structures in the complex, appear to strongly echo and to probably be antecedent to the Mesoamerican civilizations of the Olmecs (from ca. 1200 BCE) . . .
Maize (and hence agriculture) had reached the American Southwest by about 2100 BCE via a highland route from a pre-Olmec civilization in Mexico (see also here). Domesticated pumpkins and gourds were present in Kentucky ca. 3000 BCE, and were independently domesticated in Northeast Mexico and the eastern United States. Given this data, I'm skeptical that Poverty Point was really, as the investigator in the video claims, a hunter-gatherer society. But, there are authoritative investigators of the site who have reached that conclusion.

Maize only reached the Eastern United States around 200 BCE, but the Eastern Agricultural Complex had independently domesticated other plants starting around 1800 BCE. These crops included squash (Cucurbita pepo var. ozarkana), little barley (Hordeum pusillum), goosefoot or lambsquarters (Chenopodium berlandieri), erect knotweed (Polygonum erectum), maygrass (Phalaris caroliniana), sumpweed or marsh elder (Iva annua), and sunflower (Helianthus annuus).
The plants are often divided into "oily" or "starchy" categories. Sunflower and sumpweed have edible seeds rich in oil. Erect knotweed and goosefoot, a leafy vegetable, are starches, as are maygrass and little barley, both of which are grasses that yield grains that may be ground to make flour.
It is plausible to me that non-specialist archaeologists at these sites may not have recognized Eastern Agricultural Complex crops as domesticated plants rather than as wild gathered crops, since most of the EAC crops were later replaced by the maize-bean-squash triad developed in Mexico. 

Also, cooking in stone ovens seems inconsistent with a nomadic hunter-gatherer lifestyle.

It is notable that the construction of the Poverty Point mound is contemporaneous with the climate event that in Europe and the Near East led to a historical phenomena known as Bronze Age collapse. Perhaps the effects of that climate event in the Mississippi Delta area at the time spurred a fresh wave of religious devotion to assuage the gods.

Another reason to have particular interest is Poverty Point is that like Göbekli Tepe, in the Fertile Crescent, this seems to have been the point of genesis of a cultural movement that may be ancestral to a wave of agricultural development and organized civilization that spanned most of one continent and a healthy part of another in both cases. (Links to posts on subsequent possibly related civilizations in North America can be found in this post.)

In the chicken and egg problem of which came first, large scale organized religion, or modern civilization, both of these sites argue in favor of a religion first hypothesis.

LHCb Observes Five New Excited States Of A Known Heavy Baryon

Lubos Motl manages to muse poetic on the observation of five new excited neutral charmed omega baryon resonances at the LHCb experiment. I saw the paper when the pre-print was released earlier this week, and swiftly moved past it with a ho-hum. But, sometimes the most powerful stories are in the telling and not the conclusion, and Motl tells it well. (TD at Quantum Diaries Survivor tells much the same story.)

These particles should exist in the Standard Model and are predicted by QCD. They don't shake any of the known laws of physics.

The results will end up as official data points at the Particle Data Group's catalogue of experimental observations of hadrons (only the ground state and one lighter excited state of neutral charmed omega baryon had been observed until now) which are comparable to the long dull pages of data points in tables in the CRC Handbook of Chemistry and Physics about atoms and molecules. And, this will have value as long as it is easier to put data points in a table based upon experiments than it is to do the calculations from first principles needed to determine those values. (The stories linked to in the latest post at 4Gravitons gives us an inkling of hope that this might not always be the case for evermore, because research that would dramatically simplify QCD calculations if successful is continuing in earnest and making progress.)

The fact that there are five over a 119 MeV mass range is interesting for folks who don't have an intuition about how crowded the hadron mass spectrum is. The narrowness of the peaks in the chart reproduced above, called a "narrow width" means that they decay relatively slowly relative to particles with greater width. (They are still highly unstable, however, lasting only for a tiny fraction of a second.)

The naming conventions for hadrons like these is indeed unnaturally awkward. 

Also, while this is less of a big deal than it was in the early days of particle physics when people thought that all the new particles were fundamental, observing five new resonances for the first time in one experimental run is still better than par for the course in this field. It is certainly worth the self-congratulatory tweet from the lab that brought this to his attention.

UPDATE March 22, 2017: Two new papers make detailed theoretical interpretations of these five resonances: here and here.

Monday, March 13, 2017

Central African Hunter-Gatherer Ancient DNA Is Distinctive

Malawi is along the Great Rift Valley that divides Eastern and Central Africa. 
In 1950, J. Desmond Clark led excavations at a Later Stone Age rockshelter at Hora Mountain, a large inselberg overlooking a modern floodplain in the Mzimba District of northern Malawi. At the Hora 1 site, he recovered two human skeletons, one male and one female, along with a rich—but superficially described and undated—cultural sequence. In 2016, our renewed excavations recovered a wealth of lithic, faunal, and other materials such as mollusk shell beads and ochre. Our reexamination of the skeletons also produced the first ancient DNA from the central African region, which together with previous morphological analysis demonstrates that the LSA foragers of the area cannot be readily fit within the known genetic and phenotypic parameters of living foragers. The significance of the Hora 1 site was made further clear by the relocation of several previously known sites also at the mountain, the discovery of four new rock art sites, and the discovery of four very rich new archaeological sites in the mountains adjacent to the floodplain. Here, we describe our renewed work and how it fits with the original findings to offer unprecedented promise for understanding the lifeways of Holocene foragers in central Africa.
Jessica Thompson, et al., "The Forgotten Significance of the Later Stone Age Sites near Hora Mountain, Mzimba District, Malawi" (Forthcoming, SAA 2017 Conference Paper).

The late stone age site, most notably, precedes Bantu expansion.

This seems to be of a piece with the face that the substrate population in Mozambique (where Bantu populations have click consonants) likewise does not correspond to any modern African population. As previously noted at this blog in that link:
A 2010 article in the European Journal of Human Genetics found genetic traces of a substrate population in Mozambique that was an ancestral component distinct from any of the other ancestral populations of Africa. As the body text in that open access article explains (citations omitted):
The southeastern Bantu from Mozambique are remarkably differentiated from the western Niger-Congo speaking populations, such as the Mandenka and the Yoruba, and also differentiated from geographically closer Eastern Bantu samples, such as Luhya. 
These results suggest that the Bantu expansion of languages, which started ~5000 years ago at the present day border region of Nigeria and Cameroon, and was probably related to the spread of agriculture and the emergence of iron technology, was not a demographic homogeneous migration with population replacement in the southernmost part of the continent, but acquired more divergence, likely because of the integration of pre-Bantu people. 
The complexity of the expansion of Bantu languages to the south (with an eastern and a western route), might have produced differential degrees of assimilation of previous populations of hunter gatherers. This assimilation has been detected through uniparental markers because of the genetic comparison of nowadays hunter gatherers (Pygmies and Khoisan) with Bantu speaker agriculturalists. 
Nonetheless, the singularity of the southeastern population of Mozambique (poorly related to present Khoisan) could be attributed to a complete assimilation of ancient genetically differentiated populations (presently unknown) by Bantu speakers in southeastern Africa, without leaving any pre-Bantu population in the area to compare with.
In other words, there is genetic evidence that there was an entire "lost race" in Mozambique, distinct from Khoisans, Pygmies, East Africans and West Africans, with no pure blooded remaining members that disappeared when it was subsumed into the population of Bantus expanding into the area.

Those Bantus had a linguistic and cultural legacy from a quite precisely identified small region near the coastal border of Nigeria and Cameroon, but had assimilated a mish mash of Africans peoples into their genetic melting pot, including the ancestral peoples of Mozambique, on their way to Southeast Africa.

Ancient Egyptian Elites Had Less Sub-Saharan Admixture Than Modern Egyptians

Egypt, located on the isthmus of Africa, is an ideal region to study historical population dynamics due to its geographic location and documented interactions with ancient civilizations in Africa, Asia, and Europe. Particularly, in the first millennium BCE Egypt endured foreign domination leading to growing numbers of foreigners living within its borders possibly contributing genetically to the local population. Here we [examine] mtDNA and nuclear DNA from mummified humans recovered from Middle Egypt that span around 1,300 years of ancient Egyptian history from the Third Intermediate to the Roman Period. Our analyses reveal that ancient Egyptians shared more Near Eastern ancestry than present-day Egyptians, who received additional Sub-Saharan admixture in more recent times. This analysis establishes ancient Egyptian mummies as a genetic source to study ancient human history and offers the perspective of deciphering Egypt’s past at a genome-wide level.
Krause et al., "Ancient Egyptian Mummy Genomes Suggest an Increase of Sub-Saharan African Ancestry in Post-Roman Periods" (Forthcoming Society for American Archaeology 2017 Conference Paper) Via Eurogenes.

I would suggest that pretty much anyone who's reading an SAA 2017 conference paper actually knows where Egypt is even without having it explained in the first sentence of the abstract to the paper.

I would also suggest that the remains of royal or aristocratic Egyptians that survive as mummies, particularly those following the Levantine derived Hyskos 15th Dynasty (ca. 1650 BCE to 1545 BCE) in the Third Intermediate period (ca. 1070 BCE to 664 BCE), and with the Eastern Mediterranean interchange enriched Roman period, may not be representative of the larger Egyptian population genetically, any more than the genetics of royal families in Europe were in the early modern and modern periods of European history when royals were frequently foreigners.

It could be that ancient Egyptians did indeed have less sub-Saharan admixture than they do in more recent times, but it would not be at all surprising to see a class differential in population genetics in Egypt in much the same way that we do in India.

Friday, March 10, 2017

Younger Dryas, North American Extinctions And End Of Clovis Culture Tied To ET Impact

Once again, climate and extraterrestrial impacts have proven to be powerful drivers of the course of history and prehistory.

About 20,000 years ago was the peak of the ice age called the Last Glacial Maximum (LGM). That ice age was winding down when all of the sudden the "Younger Dryas", "a climatic period of extreme cooling that began around 12,800 ago and lasted about 1,400 years", began. 

According to the lead author of a new study, Christopher Moore: "the Younger-Dryas coincides with the end of Clovis culture and the extinction of more than 35 species of ice-age animals. Moore says while evidence has shown that some of the animals were on the decline before Younger-Dryas, virtually none are found after it. Moore says that would indicate an extinction event for North America." The animals that went extinct included the mastodon, mammoth and saber-toothed tiger.

Now elevated platinum deposits at eleven Clovis archaeological sites and in the Greenland Ice sheet, all at the beginning of the Younger Dryas event suggest that "the most likely source of such platinum enrichment was from the impact of an extraterrestrial object," according to Moore, probably by a comet or asteroid about two-thirds of a mile in diameter. This would be much smaller than the CT boundary impact 65 million years ago that killed the dinosaurs, however, and no impact crater has been identified. According to the paper, these findings are corroborated previous study, Andronikov et al., that "investigated sediments from Belgium, the Netherlands, Lithuania, and NW Russia near Finland, reporting sharp YDB enrichment in Pt at the YD onset, as well as other meteoritic elements such as nickel, chromium, copper, and iridium."

The literature review explains that:
The Younger Dryas impact hypothesis proposed a causal link between a cosmic impact event and a) the onset of the YD climate cooling episode at ~12,800 calendar years BP, b) a peak in continental-scale biomass burning, c) extinction of more than 35 genera of North American Pleistocene megafauna, and d) the demise of the Paleoindian Clovis technocomplex. . . . Researchers have also hypothesized a human population decline or demographic shift immediately following the disappearance of the Clovis technocomplex at the YD onset.
There was already substantial evidence linking this to an extraterrestrial impact at a quite narrow and well defined point in time according to literature review:
In support of those links, several studies have reported an exotic assemblage of impact-related proxies in a widely-distributed layer at the YDB, dating to 12,800 ± 150 Cal B.P. Impact proxies reported for YDB sites include but are not limited to high-temperature iron and silica-rich magnetic spherules, nanodiamonds, aciniform carbon (soot), high-temperature melt-glass, and elevated, above-background concentrations of nickel, osmium, and iridium. . . . Another investigation demonstrated the synchroneity of the YDB layer throughout its geographic range based on Bayesian modeling of data from 23 stratigraphic sections and 354 dates from 12 countries. The modeled YDB age range is 12,835–12,735 Cal B.P. (at 95% probability).
The abstract and the citation to the paper are as follows:
Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.). In order to evaluate its geographic extent, fire-assay and inductively coupled plasma mass spectrometry (FA and ICP-MS) elemental analyses were performed on 11 widely separated archaeological bulk sedimentary sequences. We document discovery of a distinct Pt anomaly spread widely across North America and dating to the Younger Dryas (YD) onset. The apparent synchroneity of this widespread YDB Pt anomaly is consistent with Greenland Ice Sheet Project 2 (GISP2) data that indicated atmospheric input of platinum-rich dust. We expect the Pt anomaly to serve as a widely-distributed time marker horizon (datum) for identification and correlation of the onset of the YD climatic episode at 12,800 Cal B.P. This Pt datum will facilitate the dating and correlating of archaeological, paleontological, and paleoenvironmental data between sequences, especially those with limited age control.
Christopher R. Moore, et al., "Widespread platinum anomaly documented at the Younger Dryas onset in North American sedimentary sequences." 7 Scientific Reports 4403 (2017).

Inverted Neutrino Mass Hierarchy Strongly Disfavored

New evidence very strongly favor a "normal" neutrino mass hierarchy over an "inverted" neutrino mass hierarchy.  The inverted hierarchy is disfavored by this new evidence at a 93% confidence level.

This determination is reached using a methodology based upon the "coherent forward scattering of the neutrino beam with electrons in the Earth". This much more direct method of measuring the neutrino mass hierarchy is entirely independent of the other evidence strongly favoring a "normal" neutrino mass hierarchy over an inverted. 

The other main method that is used to determine the neutrino mass hierarchy compares the estimated sum of the masses of the three neutrino mass eigenstates based upon cosmology observations to the minimum masses of the sum in the "normal" and "inverted" mass hierarchy cases based upon differences between the mass eigenstates inferred from neutrino oscillation data.

The most recent results using that methodology exclude an inverted hierarchy with a confidence level that ranges from 64% to 96% depending upon the assumptions made in estimating this probability.

The fact that two independent experimental methods both strongly favor the normal hierarchy over the inverted one, makes the combined conclusion from this experimental data, that the neutrino hierarchy is very likely to be "normal" rather than "inverted" much more robust, and probably exclude the inverted hierarchy at a 95% confidence level or more.

The abstract to the paper and the citation to the pre-print are as follows:
Results are reported from an improved measurement of νμ→νe transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^20 protons-on-target 33 νe candidates were observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA νμ disappearance data and external constraints from reactor experiments on sin^2(2θ13), the hypothesis of inverted mass hierarchy with θ23 in the lower octant is disfavored at greater than 93% C.L. for all values of δCP.
P. Adamson, et al., "Constraints on oscillation parameters from νe appearance and νμ disappearance in NOvA" (March 9, 2017).

UPDATE March 13, 2017: Another study favors a normal over inverted hierarchy by a 42:1 ratio by combining cosmology and oscillation data. In more conventional terms, this is two-sigma evidence in favor of a normal hierarchy over an inverted one.

Yamna To Montenegro To Atlantic Bell Beaker?

As we wait on the brink of a huge amount of new ancient Bell Beaker DNA, everyone is scrambling to look at the archaeology that could predict those results and provide a coherent narrative that will be able to explain them.

Gruda Boljevića tumulus is one of the most interesting and most important archaeological sites of the Montenegrin Late Copper - Early Bronze age. It is also probably one of the most important archaeological sites found recently in Europe.

The reason why I believe that this tumulus is so important, is because it shows that the dolmen building, golden cross disc making culture which developed in Montenegro in the first half of the third millennium BC, has its direct cultural roots in Yamna culture of the Black Sea steppe. Why is this important? Because the gold cross discs found in this tumulus and other Montenegrian tumuluses are later found in Beaker culture sites in Ireland and Britan. And the Irish annals tell us that the Early Irish who brought with them metallurgy and gold migrated to Ireland from Russian steppe, via Balkans and then Iberia. Gruda Boljevića is the last and most important piece of evidence which confirms that the Irish annals contain not pseudo histories, but real histories which talk about events that happened in the 3rd millennium BC...

Monday, March 6, 2017

Still No Sign Of Neutrinoless Double Beta Decay

Another year, another more strict exclusion of neutrinoless double beta decay. The latest result doubles the duration of the exclusion from the last paper from GERDA, discussed here in a post made in the summer of 2015.  

The universe is roughly 1.4*10^9 years old, so the current limit from GERDA means that no more than one in 3.8*10^16 of hadrons that could have done so have actually experienced neutrinoless double beta decay since the formation of the universe. According to the new paper cite below:

"For light Majorana neutrino exchange and a nuclear matrix element range for 76Ge between 2.8 and 6.1, the Gerda half-life limit converts to mββ <0.15–0.33 eV (90 % C.L.)."

A good definition of mββ appears on page 2 of a 2015 paper on the topic together with some other very standard definitions of some other key terms:
We use mi (i = 1, 2, 3) to denote the masses of the neutrino mass eigenstates νi . We denote with 1 and 2 the eigenstates that are closest in mass; moreover, we take m2 > m1, so that ∆m2 21 is always positive, while the sign of ∆m2 31 discriminates between the normal (NH) and inverted (IH) hierarchies, for ∆m2 31 > or < 0, respectively. The neutrino mass eigenstates are related to the flavour eigenstates να (α = e, µ, τ ) through να = P i Uαiνi , where Uαi are the elements of the neutrino mixing matrix U, parameterized by the three mixing angles (θ12, θ23, θ13), one Dirac (δ) and two Majorana (α21, α31) CP-violating phases. Oscillation phenomena are insensitive to the two Majorana phases, that however affect lepton number-violating processes like 0ν2β decay. The different probes of the absolute scale of neutrino masses are sensitive to different combinations of the mass eigenvalues and of the elements of the mixing matrix. β decay experiments measure the squared effective electron neutrino mass m2 β ≡ P i |Uei| 2 m^2 i , while 0ν2β searches are sensitive to the effective Majorana mass mββ ≡ P i Uei^2 mi , where φ2 ≡ α21 and φ3 ≡ α31 − 2δ. Finally, cosmological observations probe, at least in a first approximation, the sum of neutrino masses Mν ≡ P i mi = m1 + m2 + m3.
At this blog, I usually refer to "the neutrino mixing matrix U" as the PMNS matrix.

The quantity mββ is equal to the weighted average of the three neutrino mass eigenstates based upon the relative likelihood of an electron neutrino being in each of the mass eigenstates. This works out to approximately 0.6724 * Mv1+ 0.2916 * Mv2 +  0.0225 * Mv3, which the sum of the row of PMNS entries doesn't quite add to 1.0 as it should due to experimental uncertainties in the value of the respective entries. As I noted earlier this year the range of the three neutrino masses that would be consistent with experimental data is approximately as follows (with the location of each mass within the range being highly correlated with the other two and the sum):

Mv1 0-7.6 meV
Mv2 8.42-16.1 meV
Mv3 56.92-66.2 meV

For pro forma values of 1 meV, 10 meV and 58 meV, the value of mββ is (to spurious accuracy) equal to 4.8934. Put in more easily compatible terms mββ = 0.005 eV. So, GERDA and other neutrinoless double beta decay experiments need to be about 30 times more precise before they have any hope of meaningfully determine the Majorana neutrino mass of the neutrinos from neutrinoless double beta decay.
In fact, cosmology data and neutrino oscillation data implies that it is very likely that mββ <0.15, so the experimental data don't yet rule out a Majorana neutrino. 

But, GERDA's sensitivity is expected to increase by a factor of five over the remainder of its current experimental run over the next few years, and the combination of GERDA's results with other experiments also tweaks down the upper threshold. So, we may be just a few years away from being able to resolve the Majorana v. Dirac neutrino mass debate (or at least, from being able to rule out the most straightforward Majorana neutrino mass models). 
The Standard Model of particle physics cannot explain the dominance of matter over anti-matter in our Universe. In many model extensions this is a very natural consequence of neutrinos being their own anti-particles (Majorana particles) which implies that a lepton number violating radioactive decay named neutrinoless double beta (0νββ) decay should exist. The detection of this extremely rare hypothetical process requires utmost suppression of any kind of backgrounds. 
The GERDA collaboration searches for 0νββ decay of 76Ge (76Ge→76Se+2e−) by operating bare detectors made from germanium with enriched 76Ge fraction in liquid argon. Here, we report on first data of GERDA Phase II. A background level of ≈10−3 cts/(keV⋅kg⋅yr) has been achieved which is the world-best if weighted by the narrow energy-signal region of germanium detectors. Combining Phase I and II data we find no signal and deduce a new lower limit for the half-life of 5.3⋅10^25 yr at 90 % C.L. Our sensitivity of 4.0⋅10^25 yr is competitive with the one of experiments with significantly larger isotope mass.  
GERDA is the first 0νββ experiment that will be background-free up to its design exposure. This progress relies on a novel active veto system, the superior germanium detector energy resolution and the improved background recognition of our new detectors. The unique discovery potential of an essentially background-free search for 0νββ decay motivates a larger germanium experiment with higher sensitivity.

Human Evolution In One Chart

From here.

Friday, March 3, 2017

Two 105 to 120 ky BP Skulls From China

A new paper in the journal Science examines two skulls from 105,000 to 120,000 years ago from China. It note similarities to both Neanderthals and early modern humans in East Asia.  The authors call it "archaic Homo" without clearly venturing a hypothesis on a species.

Notably, the skulls are associated lithic technology (i.e. stone age tools) that is Middle Paleolithic, a phrase that would usually be used to describe Mousterian industry which is associated with Neanderthals. But, I have never heard of Mousterian industry this far east and it isn't clear what the authors mean by that description. On the other hand, there are bone tools present, which is usually a litmus test for the presence of modern humans rather than archaic hominins.

The use of the word "human" in the paper is slippery (as best I can tell, referring generally to members of the genus Homo rather than to Homo sapiens sapiens, i.e. anatomically modern humans) as in the following passage from a blog that appears to be quoting or paraphrasing the paper:
The layer contains a Middle Paleolithic lithic industry, along with bone tools on diaphyseal splinters, and it has produced a consistent series of optically stimulated luminescence (OSL) ages, placing the human remains at about 105,000 to 125,000 years, and the overlying layers have provided ages of about 100,000 and 90,000 years. The human crania are therefore securely dated to marine isotope stage (MIS) 5, within MIS 5e or 5d. 
The Xuchang early Late Pleistocene archaic human crania exhibit a mosaic morphological pattern. They exhibit features that are ancestral and reminiscent particularly of early Middle Pleistocene eastern Eurasian humans, and derived and shared by earlier Late Pleistocene humans elsewhere, whether morphologically archaic or modern. 
In common with other early Late Pleistocene humans (whether morphologically archaic or modern), they share neurocranial expansion and gracilization. The endocranial volume (ECV) of Xuchang 1, about 1800 cm3, is at the high end of Neandertal and early modern human variation, and its neurocranium closely approximates the shape of those of Middle Pleistocene humans, especially eastern Eurasians. 
In combination with these derived and ancestral features, the Xuchang crania also display two complexes that primarily align them with the Neandertals. They share occipital (suprainiac and nuchal torus) and temporal labyrinthine (semicircular canal) morphology with the Neandertals.
The paradigm in this area is that modern humans arrive in East Asia in the Upper Paleolithic, and that prior to that Homo Erectus is the only well described hominin species in Asia. So, it appears that the reference to similarities to "early Middle Pleistocene eastern Eurasian humans" is to similarities to East Asian Homo Erectus. Similarly, the phrase "Middle Pleistocene humans, especially eastern Eurasians" is clear as mud, as there are not other well documented anatomically modern humans in the Middle Pleistocene in eastern Eurasia, but it isn't clear what archaic hominin species is being referenced either.

But, the size of the brain case at 1800 cubic centimeters is too big to be a conventional Homo Erectus which is the only species well documented to exist that far East at that time, although it would be consistent with either Neanderthals or anatomically modern humans.

There are clear examples of Neanderthals in northern Asia as far as the Altai mountains, and there are examples of Neanderthals in southern Asia are far as Pakistan. But there has never been any clear archaeological evidence for Neanderthals at any time in India, Southeast Asia or East Asia.

There is Denisovan DNA in Melanesians and aboriginal Australians and Negritos from the Philippines, as well as very low level in mainland Asians and in island Southeast Asia west of the Wallace line of uncertain provenance. And, of course, we have ancient Denisovan DNA from a Siberian cave near the far eastern extent of Neanderthal expansion (Altai Neanderthals also show traces of modern human admixture dating to 100,000 years ago). But, we have only a tooth, a pinky bone and some DNA from the Denisovans which tells us that they were a sister clade to Neanderthals with Neanderthal admixture of their own that existed at about the right time to have affinity with these old skulls from China, but little more. This could be a Denisovan skull, but we wouldn't know without extracting ancient DNA from it (according to prefatory material in Science "the investigators have not extracted DNA" from the Chinese skulls.)


Are these skulls from early anatomically modern humans who were part of a first, almost failed wave of modern humans and has significant archaic hominin admixture?

Or, are these skulls misdated? 

Or, are these skulls from archaic hominins who were present in Asia after Homo Erectus and before anatomically modern humans, of a species not well characterized until now that might or might not be Denisovans?

Did this species, whatever it is, replace Homo Erectus in Asia?

Is this a new kind of lithic and bone industry, or does it correspond to an existing one?

Without Answers

John Hawks tweets that he doesn't think that they are Denisovan skulls. I'm not so confident. There is more commentary on this issue in prefatory material from Science which notes that:
The skulls lack faces and jaws. But they include enough undistorted pieces for the team to note a close resemblance to Ne­andertals. One cranium has a huge brain volume of 1800 cubic centimeters—on the upper end for both Neandertals and moderns—plus a Neandertal-like hollow in a bone on the back of its skull. Both cra­nia have prominent brow ridges and inner ear bones that resemble those of Neander­tals but are distinct from our own species, Homo sapiens. . . . 
However, the crania also differ from the western Neandertals of Europe and the Middle East. They have thinner brow ridges and less robust skull bones, similar to early modern humans and some other Asian fossils. “They are not Neandertals in the full sense,” says co-author Erik Trinkaus, a paleoanthropologist at Washington Univer­sity in St. Louis in Missouri. 
The skulls do share traits with some other fossils in east Asia dating from 600,000 to 100,000 years ago that also defy easy classification, says paleoanthropologist Rick Potts of the Smithsonian Na­tional Museum of Natural History in Washington, D.C. Those features include a broad cranial base where the skull sits atop the spinal column and a low, flat plateau along the top of the skull. The Lingjing crania also resemble another archaic early human skull that dates to 100,000 years ago from Xujiayao in China’s Nihewan Ba­sin 850 kilometers to the north, according to co-author Xiu-Jie Wu, a paleoanthropologist at IVPP. 
Nor are the new fossils late-occurring representatives of other archaic humans such as H. erectus or H. heidelbergensis, two species that were ancestral to Nean­dertals and modern humans. The skulls are too lightly built and their brains are too big, according to the paper. 
Wu thinks those fossils and the new skulls “are a kind of unknown or new ar­chaic human that survived on in East Asia to 100,000 years ago.” Based on similari­ties to some other Asian fossils, she and her colleagues think the new crania repre­sent regional members of a population in eastern Asia who passed local traits down through the generations in what the re­searchers call regional continuity. At the same time, resemblances to both Nean­dertals and modern humans suggest that these archaic Asians mixed at least at low levels with other archaic people.
To other experts, the Denisovans fit that description: They are roughly dated to ap­proximately 100,000 to 50,000 years ago, and their DNA shows that after hundreds of thousands of years of isolation, they mixed both with Neandertals and early modern humans. “This is exactly what the DNA tells us when one tries to make sense of the Denisova discoveries,” says paleoanthropologist Jean-Jacques Hublin of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “These Chinese fossils are in the right place at the right time, with the right features.”
This paper does not provide a conclusive answer one way or the other to these question and, if anything, it seems to obscure that statements that is does make with ambiguous terminology.

A Bridge Too Far - Some Tetraquarks Are Impossible

QCD Qualitatively Permits Composite Particles With More Than Three Quarks (Background)

In Quantum Chromodynamics (QCD) (which is widely believed to be a complete theory of the strong force, although calculations with it can only be done in approximate form) composite particles called hadrons made of two, three, four, five, sex or more quarks are not qualitatively ruled out.

In practice, almost all composite particles produced, even in very high energy experiments, involve two quark composite particles called mesons, or three quark composite particles called baryons. (The only form of "free" quark observed outside a composite particle is the top quark which generally decays via the weak force before it has time to form any kind of composite particle.)

There are quite a few composite particle resonances that are hard to characterize in a simple constituent quark model including only mesons and baryons, however, and a considerable share of research in experimental QCD is devoted to understanding these anomalous resonances.

For example, there is not a consensus understanding regarding how scalar and axial vector mesons arise and what the nature of their internal structure consists of within the QCD community. There is also a continued failure to experiment to disclose any really definitive examples of "glueballs" which are predicted to exist by QCD, despite decades of searching for them.

A pair of two quark mesons can develop a bond similar to the bond between atoms in a molecule to each other, which is called a "meson molecule". The resonances most convincingly characterized as meson molecules include X(3872), Zb(10610) and Zb(10650) in the bottomonium sector, and Zc(3900) (discovered at the BES III experiment in 2013) and Zc(4020/4025) in the charmonium sector. 

There have been only a few definitive experimental observations of true tetraquarks (as opposed to mere "meson molecules") which have a strong force bond that connects each of the four quarks to each other: the Zc(4430) confirmed to be a tetraquark the LHCb experiment in 2014 after being first observed by the Belle collaboration in 2007, is the most convincing candidate. This tetraquark observations does seem to be the real deal.

But, it and other strong tetraquark candidates such as X(4274), X(4500) and X(4700) announced by the LHCb in June of 2016 involve at least some lighter quarks. (The DZero experiment at Fermilab announced that the X(5568) resonance is also a tetraquark in February of 2016, but this finding is in doubt because it has not been confirmed by the LHCb even though it should have been visible at the LHCb by now given the amount of data that the LHCb experiment has collected if it is real.)

Experimental hints of pentaquarks have remained elusively experimentally insignificant for decades, from 1976 through the present, although five quark meson-baryon molecules have been observed, probably including some of the spin combinations of resonances known as Pc(4380)+ and Pc(4450)seen as the LHCb experiment, including particularly the spin 3/2 version of the heavier of the two resonances. The most promising candidate for a pentaquark to date is a spin 5/2 version of the hadron called Pc(4380)+, observed in 2015, but it has only been observed by one experiment in one production channel, so it isn't impossible to rule out some sort of seriously systemic error.

But, just as top quark hadrons aren't qualitatively ruled out by QCD even though they are quantitatively incapable of forming bound states (or at a minimum, extremely unlikely to form bound states, which if formed would be shorter lived than any other kind of hadron, even at extremely high energies such as those of the current run of the LHC), the fact that QCD qualitatively allows tetraquarks or higher order composite QCD particles does not mean that they are quantitatively possible.

Four Charm Quark Tetraquarks And Four Bottom Quark Tetraquarks Are Impossible; But Two Charm Quark and Two Bottom Quark Tetraquarks Might Be Possible

A rigorous but not absolutely comprehensive set of QCD calculations suggest that composite particles made of four charm quarks, and composite particles made of four bottom quarks (i.e. fully-heavy tetraquarks) are "unbound". In other words, the strong force mediated by gluons isn't strong enough to hold them together confined in a composite particle, although a bound composite particle made of two charm quarks and two bottom quarks might just barely be possible.

In other words, unless something subtle but important has been left out of the calculation, these fully-heavy tetraquarks are theoretically impossible.

The study hedges that it might have missed a subtle point because there have been some experimental observations which could hint at the existence of fully heavy tetraquarks, although these data points are very tentative and don't amount to a confirmed observation of them.

Generally, a particle is not considered discovered by particle physicists until we have five sigma evidence for it in an experiment, which has not yet happened in the case of any fully heavy tetraquarks.

The abstract of the paper and it citation are as follows:
Multiquark states have been advocated to explain recent experimental data in the heavy-light sector, and there are already speculations about multiquarks containing only heavy quarks and antiquarks. With a rigorous treatment of the four-body problem in current quark models, full-charm (ccc¯c¯) and full-beauty (bbb¯b¯) tetraquarks are found to be unbound. Thus their stability should rely on more subtle effects that are not included in the simple picture of constituent quarks. The case of (bcb¯c¯) might be more favorable if the naive color-additive model of confinement is replaced by a string-inspired interaction.
Jean-Marc Richard, et al., "String dynamics and metastability of fully-heavy tetraquarks" (March 2, 2017).

Analysis And Other Likely Implications Of The Study

Naively, this is a pretty surprising result.

In theory, because gluons are massless, like photons (although they appear to acquire mass dynamically), so they should have an infinite range. And, if gluons had an infinite range, adding more quarks to the mix, even heavy ones, wouldn't obviously overcome the ability of the strong force to bind them. But, given that in practice the strong force is a short range force, because gluons, like quarks, are always bound into hadrons (so "free gluons" are not observed), this is somewhat less surprising.

The reasons that the phenomena of confinement arises are theoretically rich, but heuristically, it has a lot to do with the fact that the strong force gets stronger with distance and energy scale, before it gets weaker again. At short ranges, quarks and gluons are "asymptotically free" (although whether the strength of the strong force trends all of the way down to zero (a "trivial infrared fixed point") or instead to a low but non-zero strength (a "non-trivial infrared fixed point"), in the limit as it approaches zero distance/momentum transfer, is an open question in QCD.

It is likely that the result from this most recent study would generalize to higher order heavy pentaquarks and hexaquarks, etc. as well. So, while QCD may allow for hadrons other than mesons and baryons, the number of composite particles that QCD allows with more than three constituent quarks is finite and quite possibly rather small. The heaviest possible tetraquark probably has a mass on the order of 16 GeV or less, if the result from this most recent study is correct, rather than the mass in excess of 22 GeV that we would expect for a four bottom quark tetraquark.

Indeed, the threshold for pentaquarks and hexaquarks would very plausibly arise with a less massive set of quarks than in the tetraquark case, because there are more quarks involved overall.

Similarly, while QCD allows for "excited states" of even its more ordinary hadrons, at some point there is so much energy in the system that it too becomes unbound as such highly energetic quarks form a quark-gluon plasma instead.

Thus, it should be theoretically possible to make a finite list of all possible composite particles bound by the strong force including all excited states, at some point (i.e. in a matter or years or a decade, not many decades or centuries), from first principles calculations.

The Relatively Narrow Hadron Mass Spectrum

The spectrum of composite particles that are not mere hadron molecules is crowded into quite a narrow mass range of about two orders of magnitude, compared to the fundamental particles whose masses span at least eleven orders of magnitude (from the lightest neutrino to the top quark). The greater range is both because the top quark and massive fundamental bosons are very heavy, and because the neutrinos, the electron, and the light quarks are very light. 

The lightest hadron is roughly 0.14 GeV and the heaviest observed hadron is about 11 GeV, a span of two orders of magnitude. The heaviest theoretically possible tetraquark would be about 22 GeV, and the heaviest theoretically possible pentaquark would be about 27 GeV (193 times as heavy as the lightest one, but still much less than the weak force bosons, the Higgs boson and the top quark). If the result of this most recent paper is correct and can be extrapolated more broadly, the heaviest possible hadron of any kind might be 16 GeV (115 times as heavy as the lighest one).

Observed mesons range from 0.13957 GeV (the charged pion) to 11.02 GeV (unclassified forms of bottomonium) (which is close to the theoretical maximum for a meson). The heaviest observed meson without bottom quarks has a mass of under 4.7 GeV, and the theoretical maximum mass of a meson without bottom quarks is probably under 5 GeV.

Observed baryons range from 0.938 GeV (the proton) to resonances (not all fully classified according to the properties and structure) of up to 5.946 GeV (e.g. the bottom Xi), although heavier baryon resonances up to about 15-16 GeV are theoretically possible. The heaviest theoretically possible baryon without bottom quarks would have a mass of under 8 GeV.

* As noted above, the heaviest confirmed or unconfirmed potential exotic hadron resonance observed is less than 5.6 GeV, even though the theoretical maximum is about 16 GeV for tetraquarks if the result from the most recent study is correct and about 22 GeV for tetraquarks if it is incorrect, with the theoretical maximum for pentaquarks and other exotic quarks being even higher. The heaviest possible tetraquark without bottom quarks if this result is correct would be about 10 GeV. 

* The lightest possible tetraquark would hinge on the interpretation given to some scalar meson resonances, some of which are interpreted by some physicists as tetraquarks and some of which has masses as low as 0.5 GeV, although there is no consensus on this point, the lightest really solid candidate has a mass of 3.9 GeV.

* Hypothetical glueballs are predicted to fall in the mass range from 1 to 5 GeV.

Experimental Implications For Hadron Physics

One of the collateral consequences of this narrow theoretically possible mass range is that even a much more powerful collider than the LHC would not be expected to discover many new hadrons simply because it is more energetic. And, the fact that we have built the LHC and created collisions are far more powerful than necessary to create the heaviest hadrons QCD predicts that they should be, without seeing any hadron resonances heavier than QCD predicts that they should be, also confirms that our model appears to be valid over a very great range of validity.

The challenge involved in creating and observing new hadrons largely involves more clever designs for colliders and detectors (e.g. in the GlueX experiment at Jefferson Labs) rather than more raw power.

Unless one is chasing the chimera of a T meson or top eta meson or theta meson (the names for hypothetical hadrons that include a top quark), more power, per se, isn't particularly helpful and can even be a problem, because it creates more noise which makes it harder to distinguish distinct hadron resonances from each other from the resulting jumble.

When it comes to hadron physics we need better experiments, not necessarily bigger ones.

QCD Still Works

In other QCD news, a retrospective analysis of data from one of the Tevatron experiments (which finished collecting data years ago) confirms that the predictions of QCD are matched in detail by experiment in measurements of subset of photons emitted from proton-proton collisions, which are not a kind of measurement that was used to devise QCD in the first place and which involves a highly complex set of underlying calculations.

So, far all its stumbles, for example, in describing some of the more exotic parts of the hadron spectrum, QCD has to be very close to a true descriptions of reality, even if the way that it is operationalized right now is not quite perfect and stumbles now and then.

The abstract and paper are as follows:
A measurement of the inclusive production cross section of isolated prompt photons in proton-antiproton collisions at center-of-mass energy s√=1.96TeV is presented. The results are obtained using the full Run II data sample collected with the Collider Detector at the Fermilab Tevatron, which corresponds to an integrated luminosity of 9.5fb−1. The cross section is measured as a function of photon transverse energy, EγT, in the range 30<EγT<500GeV and in the pseudorapidity region |ηγ|<1.0. The results are compared with predictions from parton-shower Monte Carlo models at leading order in quantum chromodynamics (QCD) and from next-to-leading order perturbative QCD calculations. The latter show good agreement with the measured cross section.
CDF Collaboration, "Measurement of the inclusive-isolated prompt-photon cross section in pp¯ collisions using the full CDF data set" (March 2, 2017).

A Footnote On Author Credits In Article Citations

I heartily endorse the practice of crediting papers in the particle physics field and other fields where stable collaborations of large numbers of people contribute to a corporate collaboration author, such as in the paper above, possibly with a corresponding author who writes up the paper and takes responsibility for it even though others were critical in doing the work, as opposed to the older practice of publishing papers with hundreds of authors who often didn't read the paper (even if they were given an opportunity to) and made a more generalized contribution to the collaboration.

Better still is the rare but worthwhile practice which I have seen in only a handful of papers, of stating in the abstract or introduction to the paper which author was the primary contributor to which part of the total paper.