Placentation in sloths

Placenta and fetal membranes of Hoffmann's Two-toed
Sloth (Choloepus hoffmanni) from Turner 1872

Two recent papers cast light on the evolution of sloths. Delsuc and colleagues obtained mitochondrial genomes from living and extinct sloths (here) while Presslee and colleagues used proteomics to describe Type I collagen - likewise from extant and extinct species (here). They agree that notions of sloth evolution based on morphology need revision. 

It was confirmed that two-toed and three-toed sloths are not closely related and group with different forms of ground sloths. A third group with a suspensory life style was found to have diverged even earlier. These sloths crossed a land bridge to the Greater Antilles and went extinct just a few thousand years ago.

Interhaemal barrier of the pale-throated three-toed sloth
(Bradypus tridactylus) Courtesy of Allen C. Enders

Together with anteaters and armadillos, sloths belong to the ancient superorder Xenarthra. Armadillo placenta has been studied in some detail. It is villous haemochorial (discussed here). Anteater placentation is rather similar (previous post). Sloths are different. As shown by Turner, the placenta is lobulated in appearance. It is labyrinthinre and endotheliochorial (here).

Given current opinion on the relations between sloths (Folivora), anteaters (Vermilingua) and armadillos (Cingulata), parsimony dictates that their common ancestor would have had a villous haemochorial placenta. Thus the sloth placenta represents a derived state. The most recent common ancestor of two-toed and three-toed sloths lived >25 million years ago whereas sloths diverged from anteaters >50 mya. 

Lagoa Santa skulls still perplex Danes

Peter Wilhelm Lund (1801-1880)
Danish National Library (public domain)

When Peter Lund excavated human remains from Sumidouro Cave he was thoroughly perplexed. Not least because they were jumbled together with the bones of an extinct megafauna. This was in 1840 so well before Darwin had published On the Origin of Species (which cites Lund's work).

The skeletons were shipped to Copenhagen and examined there by several distinguished anthropologists (Lund never returned to Denmark). The consensus that arose was that "Lagoa Santa Man" was unrelated to present-day Native Americans. 

Springer 2017: ISBN 978-3-319-57465-3

Research and debate was renewed in the last century with new excavations in the caves near Lagoa Santa (now a suburb of Belo Horisonte). A key find was Luzia, a skull feared lost in the recent fire at the National Museum in Rio de Janeiro (previous post) (it survived but suffered heat damage). This skull was dated to 11,000 years ago.

Comparisons have been drawn between the features of the Lagoa Santa skulls and those of Australasian peoples such as Andaman Islanders. What can genomics tell us? A first set of clues hinted at an early wave of migrants designated "Population Y" who left a genetic signature that is strongest in some isolated Brazilian communities (see my review of David Reich). 

Skull from Sumidouro Cave excavated by Peter Lund

Now a Dane has ventured into the Lund Collection and extracted ancient DNA from a 10,400 year-old skull. The results appeared in Science last December (here). Eske Willeslev and his group found a clear Australasian genomic signature that was absent in other ancient remains from the Americas. They concluded this signal, "implies that an early group possessing it had disappeared or that a later-arriving group passed through North America without leaving any genetic trace." A conclusion echoed by the lead author, José Victor Moreno-Mayar, who simply said (here), "How did it get there? We have no idea."

It seems the Lagoa Santa remains are just as perplexing to Willerslev as they were to Lund and for a similar reason: they do not neatly fit into the scheme of things.

Postscript

The Willerslev paper is really worth reading. It builds on earlier work to confirm that Native Americans (other than Inuits) derived from a group that split from East Asians and resided in Beringia (Ancient Beringians). As they advanced into the Americas at the end of the Ice Age there was an early split into Northern (NNA) and Southern Native Americans (SNA). The SNA dispersed rapidly south of the remaining ice some 14,000 years ago. In a later phase there was admixture from a population in Mesoamerica that migrated both north and south. Another paper on ancient DNA from the Reich group also found evidence for rapid expansion into South America (here), but did not have Lagoa Santa in the data set.

Why Luzia was important

Cast of the skull known as Luzia as displayed at
National Museum of Natural History Washington DC
Photo by Ryan Somma CC BY-SA 2.0

Luzia was excavated from Lapa Vermelha, Minas Gerais, Brazil and was the oldest human fossil from South America. She was found in strata dated to 11,000 years ago. Whilst casts of the skull exist elsewhere the original was lost (at best severely damaged) in the catastrophic fire that destroyed the National Museum in Rio de Janeiro. 

Luzia Woman belonged to an ancient population formerly known as Lagõa Santa Man or Paleoamerind. The first to excavate such skulls was the Danish Naturalist Peter Lund, who found them as far back as 1840. Based on the classical craniometric criteria used by anthropologists until well into the twentieth century, this population clearly diverged from all others in North and South America.

Lagõa Santa skull excavated 1840 by Peter Wilhelm Lund

There is an interesting correlate in modern genomic data. David Reich and colleagues postulate an ancient Population Y corresponding to a genetic signal borne by the Surui people of the Amazon region (discussed here - see previous post for Reich's book where this is further discussed). The interesting thing about this signal is that it is shared with the faraway Andaman Islanders and natives of New Guinea and Australia.

We already know of two branches to the population that crossed the Bering Strait and peopled North and South America - thanks to work by Eske Willerslev's group (here). Was there a third branch that gave rise to the Paleoamerinds or even a separate and earlier migration?

To piece this together it would have been useful to extract ancient DNA from the Luzia skull. That had not been done prior to the fire. There are other skulls around including those excavated by Peter Lund and now housed in Copenhagen. They may yet yield new pieces to complete the puzzle.

Who We Are and How We Got Here

Oxford University Press 2018
ISBN 978-0-19-882125-0

In little more than a decade, studies of ancient DNA have transformed our knowledge of human history. A recurrent theme is the migration of people over long distances to mingle with and often to replace existing populations. Often the immigrants brought with them new technologies and languages. Although there are also examples of skills dispersing without migration (spread of the Beaker culture from Iberia) and succesive waves of migrants adopting local languages (southwest Pacific islands).

All this and much more is related in David Reich's new book. Although his prose is stilted at times, that is more than compensated by the breadth of material presented and by excellent diagrams. These include maps showing the probable origin, direction and timing of human migrations. 

Skull from Lapa Vermelha, Lagōa Santa, Brazil
Photo by Ryan Somma CC BY-SA 2.0

Although Reich delights in disproving established concepts, it is interesting to find that some long-standing ideas receive support. For example, there is a clear genomic evidence of two waves of migration into Central and Southern America. The first wave of migrants designated "Population Y" left a genetic signature that is strongest in some isolated Brazilian communities (Tupí). This finding lends support to the concept of an ancient people called Palaeoamericans by Neves (here) and named a century ago as Palaeo-Amerind by Haddon (previous post). These ideas were fostered by excavations at Lagõa Santa, Brazil, started 175 years ago by the Danish scientist Peter Lund and continued until this day.

Similarly, present day peoples of India derive much of their genetic makeup from two previous populations. One of these described as "Ancestral South Asians" bears a striking resemblance to the "Pre-Dravidians" postulated by Haddon.

There has been some animus engendered by Reich's book - exacerbated by an opinion piece he wrote for The New York Times. Part II of the book has chapters on the origins of Europeans, South Asians, Native Americans, East Asians and Africans. Inevitably this division reflects the broad racial categories of the past. The flight from racial stereotyping in the last 50 years is laudable, but a mist of political correctness can make recent studies hard to decipher. Reich's book disperses the mist and inevitably invites controversy. 

Przewalski's horse an also-ran

Przewalski's horse Photo by Claudia Feh

CC BY-SA 4.0 

Przewalski's horse has long been seen as the last population of wild horses. No more. A new attempt to find the origins of domestication using ancient DNA is full of surprises (here). 

The Botai Culture of Central Asia has been tied to domestication of horses some 5500 years ago. Ancient DNA was extracted from the bones of Botai horses and the genomes compared with those of other ancient and modern horses.

Cord at term of Przewalski's horse

From Benirschke Comparative Placentation

The first surprise was that Przewalski's horse clustered with the Botai horses. The inescapable conclusion is that Przewalski's is a feral population descended from those domesticated at Botai.

The second finding was that all other horses descend from a separate branch. This was foreshadowed in a previous study (previous post). The most parsimonious explanation is that there was a second centre of domestication yet to be identified.

Benirschke has several images of the placenta of Przewalski's horse (see also previous post).

Tree shrews move from branch to branch

Species tree by three coalescent-based approaches
from Esselstyn et al 2017 © The Author 2017

In an heroic effort to resolve some of the difficult nodes in the mammalian tree, Esselstyn et al. used data from published genomes and added new data for a total of 100 mammals. Focussing on ultraconserved elements, they analysed all this by a battery of techniques, These included the classical maximum likelihood (ML) on concatenated data and three coalescent-based approaches. How did they do?

The first problem was to resolve the root of the eutherian tree. Here they did rather well. Both the ML tree and two of the coalescent-based methods gave strong support to the Atlantogenata hypothesis, i.e. a sister relationship between Afrotheria (elephants, dugongs, tenrecs and hyraxes) and Xenarthra (sloths and armadillos) with a common ancestor basal to Boreoeutheria (all other eutherian mammals).

South American Tapir (Tapirus terrestris)

Photo by Bernard Dupont CC BY-SA 2.0

They did almost as well with the second problem: the sister group to horses, rhinos and tapirs (Perissodactyla). In most analyses the found Cetartiodactyla (cetaceans and even-toed ungulates) as sister to Perissodactyla. However, they could not rule out one of the alternative hypotheses, which had bats (Chiroptera) as the sister group.

Whereas horses and cetartiodactyls (including ruminants, pigs, dolphins) all have epitheliochorial placentation, no bat does, so I am happy with their majority finding!

Pen-tailed tree shrew (Ptilocercus lowii)

From Wolf 1848 via Wikipedia Commons

On the third thorny problem the exercise failed. Tree shrews used to be thought the closest relatives to primates but have been toppled from this position in favour of colugos (previous post). Because some previous studies did not even include colugos, the present authors sought a remedy in including two colugos and three tree shrews, including the pen-tailed tree shrew above. The hope was that high taxon coverage would give a sounder result. But they were forced to conclude that placement remains uncertain. Tree shrews may be sister to rodents and lagomorphs (Glires) or to colugos plus primates (Primatomorpha).

Fortunately they could confirm colugos as sister to primates, which was the basis for my recent paper with Andrea Mess on the evolution from labyrinthine to villous placentation (here).

Congratulations Camilla Whittington

Camilla Whittington with sea horses University of Sydney

Viviparity and pregnancy has evolved numerous times and Camilla Whittington has set herself the ambitious task to seek similarities in gene expression that support pregnancy in sea horses, viviparous lizards and marsupial mammals. Her paper on the transcriptome of the brood pouch of a male sea horse was highlighted in a previous post.

Now I am delighted to report that Camilla has been awarded a Fondation L'Oréal Women in Science Fellowship. It is good that this award exists and especially encouraging that research in comparative biology of pregnancy has become known to a wider public through the publicity surrounding Camilla's Award.

Sea horses from Camilla's web site

To learn more about Camilla's Work visit her web site. For hard science you can read about the comparative genomics of hormone signalling in the chorioallantoic membrane here.

Mammal tree of life still not resolved

Lesser hedgehog tenrec (Echinops telfairi)
A member of the superordinal clade Afrotheria
Photo by Wilfried Berns CC BY-SA

My studies of placental evolution were stimulated by the large-scale molecular phylogenetic analyses of mammals that appeared 15 years ago (e.g. here). Especially riveting was the revelation of four superordinal clades, among them Afrotheria. 

An excellent review of the progress made in molecular phylogenetics and phylogenomics in the last 15 years recently appeared under the heading "Mammal madness" (by Foley, Springer and Teeling here). 

Competing hypotheses on the root of the mammalian tree
From Mess and Carter (here) based on Springer (Chapter here)



Some of the uncertainties arising from the earlier work remain. Most striking is the failure unequivocally to root the tree. The three competing hypotheses shown above are still in play. While consensus is tipping in favour of Model A above, retroposon analysis provides similar support for all three.

This is not all. There remains uncertainty about the branch order within Laurasiatheria, which includes bats, carnivores, pangolins and even- and odd-toed ungulates.

Such uncertainties make it difficult to plot the evolution of fetal membranes and placentation. Thus the likelihood that the common ancestor of extant eutherians had an endotheliochorial placenta is greater under Model A than the other two hypotheses (shown here).

Concatenation and coalescence

Analysis of large data sets involves some fancy statistics. Foley et al. give a fair account of the pitfalls in concatenation, used in all the early papers, and coalescence. Coalescent methods require much more computer time and are not applicable to large data sets unless short cuts are taken. So far this has not worked out too well.

An article just appeared in Cladistics (here), which seems to demand a "correction," in reality a retraction, of a paper in PNAS based on a coalescent approach. The authors doth protest too much, methinks. As Foley et al. point out, some pretty weird results appeared in the early days of DNA studies, too.

Morphology and molecules

The attitude of some researchers to morphological data could also be more generous. Attempts to integrate morphology and molecules, such as O'Leary et al. (previous post) do throw up some counterintuitive results. But there are examples where fossils have been useful in bolstering hypotheses based on molecular data - the position of whales is a case in point (previous post). Similarly, Afrotheria is not well supported by morphology, but we have published an apparent synapomorphy in the form of the allantoic sac (here).

Moreover fossil calibrations are the key to solving another conflict, which concerns the timing of ordinal diversification of mammals. Deservedly this is given close attention in Foley et al.'s excellent review. The sort of fossils we are talking about are too old to yield ancient DNA so we have only morphology to go on.

Foley et al. finish on an optimistic note and predict the next 20 years of phylogenetic research "should result in the resolution and dating of the mammal tree of life."

 



A colugo genome at last

Phylogenetic placement of colugos  (Scandentia) in the lineage of primates
From Mason et al. Sci Adv 2016 (here) CC BY-NC

Used to be that tree shrews (Scandentia) were regarded as the closest relatives to primates as cogently argued by Wilfrid Le Gros Clark. Molecular phylogenetics have brought that into question with some proposing colugos  or "flying lemurs" (Dermoptera) as a better alternative. But there have several competing hypotheses (see Martin). Choosing the right one has been difficult in the absence of a colugo genome.

Now that has been rectified in a comprehensive study by Mason and colleagues (here) who sequenced the genome of a Sunda colugo and compared it with genomes from 21 mammals. The result clearly came out in favour of colugos as the closest relatives to primates, supported by  20 shared indels and 16 shared retrotransposons.

There are many morphological similarities between tree shrews and colugos but the tree constructed by Mason et al. implies these are due to convergent evolution. Within Euarchontoglires they find tree shrews as the sister to Glires (rodents and lagomorphs).

Museomics and hidden biodiversity within colugos

Colugo fetus and placenta at term; ys = yolk sac;
pat = patagonium From Hubrecht 1894 (here)

Current reference works recognize no more than two species of colugo: Sunda Colugo (Galeopterus variegates) and the Phillipine Colugo (Cynocephalus volans). Mason et al. conclude that there may be as many as 6 Sundaic species and 2 Phillipine ones. They reached this conclusion by extracting DNA from museum specimens of known provenance. As an example, the Eastern and western populations on Borneo are highly divergent consistent with topographical features creating barriers to dispersal.

Currently we are re-examining the placenta and fetal membranes of colugos. We too have had to rely on museum specimens such as those collected by A.A.W. Hubrecht.

The importance of museum collections has been highlighted before in this blog. It is nice that scientists other than morphologists have discovered their value and coined the term museomics for studies of DNA from ancient specimens. Those in the current study ranged from 28 to 121 years old. The oldest specimen from the Raffles Museum of Biodiversity Research is contemporaneous with those collected by Hubrecht for his study of the fetal membranes and now housed at Museum für Naturkunde in Berlin. 

Genome of the spotted gar

Spotted gar (Lepisosteus oculatus)
Brian Gratwicke  CC BY 2.5 (Wikimedia Commons)

Not all bony fish are teleosts. Teleostei is an infraclass of ray-finned fish (Actinopterygii) with bichirs, sturgeons and gars (some 50 species) all basal to to the more numerous teleosts (some 30,000 species). The phylogeny of bony fishes has been largely resolved by Near et al. (open access).

Alligator gar (Atractosteus spatula) Moon Lake, Mississippi. March 1910, Photographer D. Franklin,
American Museum of Natural History (public domain)

 

Romer's Man and the Vertebrates did not make much of garpikes, but did include a great photo (shown above) of the largest species. My yellowing copy predates the genetic code yet alone genomics.

What we now know is that teleosts are characterized by the Teleost Gene Duplication (TGD). This event was followed by rapid sequence evolution that may explain their success as a group. It can, however, make it difficult to identify orthologs to tetrapod genes and frustrate interpretation of data obtained in zebra fish (Danio rerio). To provide a bridge, Braasch et al. have sequenced and have just published the genome of the spotted gar (open access).

To my knowledge no living species of the gar family is viviparous.

The trouble with tree shrews

Pen-tailed tree shrew (Ptilocercus lowii)
By Joseph Wolf (1820 – 1899) [Public domain] via Wikimedia Commons

Tree shrews show so many resemblances to primates that the eminent anthropologist Wilfred Le Gros Clark included them in the same order. Molecular phylogenetics refuted this but placed them in the same clade or superorder (Euarchontoglires) as primates, colugos, rodents and lagomorphs. There has been much discussion about whether colugos (previous post) or tree shrews are the closest relatives to primates.

Just how troublesome tree shrews have become is highlighted by a new paper on mammalian evolution by Tarver et al. (here).  

Alternative roots to the mammalian tree from Mess & Carter (here)

In addition to Euarchontoglires, there are three major clades of placental mammals. But there has been considerable disagreement about how to root the tree with three hypotheses as shown above.

Tarver et al. attempted to resolve this using a huge amount of genomic data and more sophisticated modelling techniques. They argue convincingly for the hypothesis at the top of the diagram where Afrotheria and Xenarthra are sister groups in a clade called Atlantogenata.

But once again tree shrews caused trouble. In a consensus tree based on protein-coding genes, tree shrews were basal to Glires (rodents and lagomorphs). This is in agreement with another recent study (here). But in a separate data set based on genes for microRNA tree shrews were basal to all the other orders in Euarchontoglires. So much so that the clade itself collapsed as a valid taxon. Naughty tree shrews!

Placentation in several species of tree shrew was studied by Luckett (here) and later in Tupaia glis by Kaufmann (here and here). The placenta is labyrinthine and endotheliochorial. So far nobody has looked at a placenta from the pen-tailed tree shrew (pictured above). It occupies its own family and a new paper (here) characterizes it as a living fossil that has undergone little change since the Oligocene.

Incidentally, pen-tailed tree shrews have a large intake of fermented nectar from the bertram palm (described here); see this blog for "boozing tree shrews."

Sea squirts, lancelets and acorn worms

A sea squirt (Ciona intestinalis) - a member of Tunicata 
Wikimedia Commons uploaded by perezoso (GFDL)

Genomics has clarified our position in the tree of life. To explain this I need to define some taxonomic terms.

Phylum Chordata comprises three subphyla: Vertebrata (Craniata), Tunicata (Urochordata)and Cephalochordata. Tunicates include sea squirts  such as Ciona (pictured) above. A familiar cephalochordate is the lancelet Branchiostoma lanceolatum better known as Amphioxus (shown below).

Amphioxus or Branchiostoma lanceolatum
(c) Virginia Gewin here (CC-BY-SA 3.0)

Amphioxus has long been used to exemplify the general plan of chordate organization and lancelets used to be regarded as the closest relatives to vertebrates. The genomic evidence, however, has tunicates like the sea squirts as sister group to vertebrates with cephalochordates as a deeper branch. Additional support is given by conserved molecular signatures (here).

Chordates belong in the Superphylum Deuterostomia (brilliantly reviewed by Lowe et al. here) along with Phylum Hemichordata and Phylum Echinodermata. Echinoderms are richly represented in the fossil record and the five extant classes include sea urchins, sea cucumbers and starfish. Hemichordates include the acorn worms for which two genomes just became available (here and here).

Acorn Worms (Hemichordata: Enteropneusta)
from Spengel 1883 (public domain)

One of many findings was a cluster of six genes that are conserved across chordates and implicated in patterning of gill slits. This is significant because gill slits were an innovation in the deuterostome lineage (although secondarily lost in echinoderms).

Relationships between deuterostome phyla were largely worked out through their embryology, an example being the erection of Chordata by Haeckel. Understanding the genes involved in developmental processes remains a focus in working out our evolutionary history (see the review by Lowe et al. mentioned above).

Clan of the cave bear: researching ancient DNA

Reconstruction of a cave bear (Ursus spelaeus)
Uploaded by Sergiodlarosa to Wikimedia Commons (CC)

The proceedings of a Royal Society discussion meeting on ancient DNA have just been published (here). Three reviews in particular captured my interest.

Ancient DNA: the first three decades by Hagelberg, Hofreiter and Keyser (here) is a lucid account of the history of the field (a major advance was shotgun sequencing as applied to the cave bear). It highlights not only high profile papers from Nature and Science (some of them reviewed in my blog), but also gives credit to important follow up studies from specialist journals. A very useful ressource indeed!

Ancient genomics by Der Sarkissian et al. (here) is from the renowned Centre for GeoGenetics in Copenhagen. This review is especially strong on the technical advances in the field and even includes a user's manual. With the techniques initially available it would have required 180 kg of material and 130 million amplicons to generate a first draft of the cave bear genome. A lot has happened since then. They conclude that even "Looking back 5 years, no one could have predicted the current state of current genomics."

Almost 20 years of Neanderthal palaeogenetics by Sánchez-Quinto and Lalueza-Fox (here) does a remarkably good job of surveying what has been learned from the DNA of Neanderthals from various geographical locations. It covers more than just their relations to and interbreeding with Denisovans and modern humans (previous post). A great deal can be inferred about their demographics, population size and ultimate extinction.

ISBN 0-517-54202-1

 The title of this post is of course an homage to the fiction of Jean M. Auel. The clan of the cave bear are Neanderthals who interact (and interbreed) with modern humans. First published in 1980 it far anticipated the scientific evidence given in the above reviews.

A. C. Haddon

Mask of turtle shell plates made by Torres Strait Islander and described by A. C. Haddon
Creative Commons (CC BY-NC-SA 4.0) The Trustees of the British Museum

Alfred Cort Haddon was a marine zoologist who  morphed into an eminent ethnologist and anthropologist after joining an expedition to the Torres Strait in 1898.

The Torres Strait Islanders are a Melanesian people distinct from the Aborigines of mainland Australia. Haddon collected their artefacts avidly -- convinced that their culture would soon be repressed by zealous missionaries. I had an opportunity to view some of these artefacts on a recent visit to the Queensland Museum in Brisbane. Haddon donated also to the British Museum, but the bulk of his Collection is now in the Museum of Anthropology and Archaeology at Cambridge University.

Alfred Cort Haddon (1855-1940)
The Wellcome Museum, Wellcome Images (CC BY 4.0)

Haddon's Collection was key to a 2011 study that examined the origin of the Australian Aborigines (here). A genomic sequence was obtained from a hair sample that had been collected in the 1920s as Haddon passed through Golden Ridge, near Kalgoorlie, Western Australia. Ethical concerns about using this material were allayed when it could be shown, with the aid of contemporary newspaper reports, that the sample was donated voluntarily. The main finding was that Aborigines are descendents of a human dispersal out of Africa that was separate and much earlier than that giving rise to present day Asians.



Cambridge University Press 1924 (Second and Revised Edition)

Human genomics has greatly improved our understanding of the migrations that gave rise to modern peoples. Haddon would have been fascinated. He did what he could with the tools then available to him and summarized them in the above book. The title was not as controversial at the time as it might be considered today.

Domestication of horses

Przewalski's horse - no longer seen to be a direct
ancestor of domestic breeds. Photo by Chinneeb (CC)
 

A large consortium has just reported on the genome of horses (Equus caballus) from the Siberian permafrost (here). The two specimens were estimated to be 16 and 42 thousand years old. Thus they were from before the start of domestication as known from the archeological evidence.

Horse phylogenetic relationships from Schubert et al. (here)
(c) The Authors

The phylogenetic analysis showed as expected that the ancient specimens (purple) are basal to all living members of the E. caballus species. However, while most genes present in domesticated breeds were found in the ancient genomes, many were missing from the Przewalski horse genome. It is perhaps a distant cousin rather than a direct ancestor of the domesticated horse (see commentary here).

Section through umbilical cord of Przewalski's horse
From the Benirschke web site (here)

So there have been two paths of selection: one through selective breeding (resulting in both desirable and deleterious traits) and the other through natural selection resulting in Przewalski's horse.

 

Placenta and implantation site of Przewalski's horse.
From the Benirschke web site (here)

These conclusions are in line with those made after sequencing the genome of a really old horse from the Middle Pleistocene (see previous post).

A Denisovan signature in modern Tibetans

Tibetan family attending a horse festival (CC) Antoine Taveneaux 

Tibetans are adapted to life at high altitude. Compared to more recent arrivals, notably Han Chinese, they have much lower rates of fetal growth restriction and fewer pregnancy complications (reviewed here).

For non-adapted populations, long-term residence and high altitude can lead to chronic mountain sickness, which is characterized by high levels of haemoglobin. However, the erythropoietic response to low ambient oxygen is blunted in Tibetans. Recent studies have ascribed this to a variant allele of EPAS1, the gene that encodes hypoxia-inducible factor 2alpha (HIF2a) (here).

In the current issue of Nature, Huerta-Sanchez and others confirmed that the gene had a highly unusual haplotype in Tibetans (here). It occurred rarely in Han Chinese and was entirely absent in a larger set of worldwide populations. Interestingly, however, it could be detected in the genome af an ancient hominin population, the Denisovans (see previous post). The conclusion drawn is that the EPAS1 haplotype of Tibetans derives from admixture between modern humans and Denisovans.  

Placental hormones and syncytins in the blind mole rat

A blind mole rat Spalax ehrenbergi
(Wikimedia Commons)

Mole rats (Spalacidae) occupy a basal position in the superfamily Muroidea. The blind mole rats, Spalax spp., are highly adapted to a subterranean lifestyle. They are resistant to both spontaneous cancer and carcinogens. For all these reasons they are widely studied and now we have a description of the genome of one species S. galili and the placental transcriptome both of that species and of S. carmeli (here).

Placental hormones

Placental-specific genes known from mouse and rat (Muridae) include cathepsins, placental lactogens (derived through duplication of the prolactin gene) and pregnancy-specific glycoproteins (reviewed here). Orthologues of many of these genes were present in Spalax and given the basal position of Spalacidae this indicates they had started to diversify in the last common ancestor of the muroid rodents.

Syncytins

Syncytins are endogenous retroviral envelope proteins thought to be essential for the formation of syncytiotrophoblast (previous post). Two such genes are known from mouse, rat (Muridae) and hamster (Cricetidae). Both are present in the Spalax genome although only Synb was confirmed in the placental transcriptome. This extends the timing of the env gene capture further back in time to an estimated 45 Mya.

Globin genes

Beta globin genes code for the two chains of haemoglobin molecules. One of them HBG is expressed in the embryo of most mammals but in the fetal haemoglobin of higher primates (discussed here). The HBG of Spalax shows evidence of rapid sequence evolution under positive selection. It is not clear to what extent this affects its affinity for oxygen.

Horses from the permafrost and beyond

Remarkably it has proven possible to sequence the genome of a Middle Pleistocene horse from a bone preserved for 700,000 years in the Canadian permafrost (summary and links here). Comparison with the genomes of modern horses and a more recent fossil yielded several interesting results. Among them, Przewalski's horse was shown to be a wild subspecies uncontaminated by domestic breeds.

Placenta and implantation site of Przewalski's horse

From the Benirschke web site (here)

Przewalski's horse was once listed as extinct in the wild but a successful captive breeding and release program has changed its status to endangered. There are several images of the placenta of Przewalski's horse on Benirschke's web site (see previous post). The equine placenta is epitheliochorial and has microcotyledons as pictured above.

Soft tissues usually are not preserved for posterity but a putative placenta accompanies a Middle Eocene fossil of the equid genus Propalaeotherium (cited here).

More news from Denisova

Denisova Cave, Altai Mountains, Siberia

ЧуваевНиколай at ru.Wikipedia

At various times the Denisova Cave has been occupied by modern humans, Neanderthals and the eponymous Denisovans. For the latter we have too few bones to reconstruct a skeleton yet enough DNA to explore the genome (here). The results indicate that there was gene flow between Denisovans and modern humans as previously shown for Neanderthals.

In a preliminary report (here) we learn that a group led by Svante Pääbo has sequenced the genome of the Neanderthals that lived at Denisova. They were a population distinct from those in Croatia and the Caucasus (for which there also is genomic data). Interbreeding between humans and Neanderthals is more likely to have occurred in the Caucasus than at Denisova.

Intriguingly, however, the study found evidence of interbreeding between the local Neanderthals and the Denisovans and - even more remarkably - evidence of contribution to the Denisovan gene pool of yet another hominin.

Possible significance for human reproduction

The highly polymorphic HLA class-I antigens (HLA-A, -B and -C) play important roles in the immune response to infection as well as in reproduction. A previous study (here) showed that interbreeding with archaic populations, and subsequent conservation by natural selection, has made a significant contribution to the HLA system in human populations outside Africa.

Some of the introgressed HLA allotypes code for proteins that are ligands for killer-cell immunoglobulin-like receptors (KIRs) including ones thought to be important in relation to human reproductive failure (here).

Work is in train to align the genomes of the chimpanzee, Neanderthals, Denisovans and modern humans. The secrets revealed by the remains from Denisova may ultimately contribute to our understanding of human reproduction.

Genome of the Coelacanth

West Indian Ocean coelacanth (Latimeria chalumnae) Wikimedia Commons

I remember how exciting it was when the second specimen of a coelacanth was caught in 1952. This "living fossil" was widely reported in the newspapers. Perhaps it was a formative moment.

Now the coelacanth genome has been sequenced and annotated (here).

The coelocanth is oviviviparous. Five fully developed young with attached yolk sacs were found in the right oviduct of a female specimen at the American Museum of Natural History (here). There was no indication of placentation but it is but a short step from ovoviviparity to placental viviparity - the more critical step being evolution of intromission.

The new report applied phylogenomics to look for genes that might have been significant in the transition from water to land. A number of developmental genes present in the coelocanth were lost in tetrapods. However, Hox genes, which determine overall body plan, were well conserved. An interesting exception was Hoxa14 and hereby hangs a tale. A conserved non-coding element associated with Hoxa14 in the coelacanth (HA14E1) was retained in tetrapods. It is speculated that it might have been recruited to coordinate nearby genes (Hoxa13, Hoxa11 and Hoxa10) that are critical in formation of mammalian fetal membranes.