Evolution of flowering plants

Amborella trichopoda, basal to all other flowering plants
(Wikimedia Commons)

Amborella is a sprawling shrub endemic to New Caledonia. This monotypic genus is basal to the angiosperms and sister to all other flowering plants. Now its mitochondrial and nuclear genomes have been sequenced and this is the subject of three papers in the current issue of Science (summarized here).

Amongst other things it addresses Darwin's "abominable mystery" - the question of why flowers suddenly proliferated on earth millions of years ago (discussed in this press release). It confirms, as had previously been suspected, that the evolution of flowering plants was preceded by a genome duplication.

Whole genome duplication has also played a significant role in the evolution of vertebrates (reviewed here). Tandem duplication of genes or groups of genes is common in the mammalian lineage and the basis for the evolution of placental hormones and fetal hemoglobins (my review here).

Footnote: In botany, placentation refers to the manner in which the ovules are attached within the ovary. It is an important taxonomic feature.

Placental gas exchange in ground squirrels

Golden-mantled ground squirrel (Callospermophilus lateralis)

(Wikipedia Commons)

Fetal blood tends to have a higher oxygen affinity than maternal blood. This aids oxygen transfer across the placenta. Some mammals (human, sheep) have a special fetal hemoglobin. In many others, hemoglobin is the same in fetus and mother, but in fetal blood it has increased affinity for oxygen because the red blood cells have a low content of DPG (here). This is the case in the few rodents studied so far.

Ground squirrels cannot use this trick. A new study (here) found that even adults have hemoglobin of high oxygen affinity and there is no effect of raising or lowering DPG.

Placenta of the golden-mantled ground squirrel from Carter and Enders (here)

© Carter and Enders 2004; Licensee Biomed Central Ltd.

So is oxygen transfer across the placenta of ground squirrels likely to be less efficient than, say, in a rat? Probably not. The same study established that an unusually large Bohr effect (defined here) aids unloading of oxygen to the tissues of ground squirrels. In any placenta there is a double Bohr effect because, as fetal blood takes up oxygen, it unloads carbon dioxide, while the opposite occurs in the maternal blood (discussed in detail here).

The new study concerns ground squirrels living at low and high altitude. The authors speculate that hemoglobin evolved to meet the demands of their fossorial life style. This in turn made it easier to expand into mountainous habitats. They did not consider the possible impact on reproduction - but perhaps they should.  

 

Transgenic monkeys

Common marmoset (Callithrix jacchus) Wikipedia Commons

A news article in Nature (here) tells how new gene-editing techniques offer the opportunity to create transgenic primates. The emphasis is on neuroscience and models of brain disease. But if transgenic lines are developed there should be placentas available for study.

Although work on rhesus macaques is mentioned, more progress has been made using marmosets. One advantage might be that marmosets usually carry twins so a colony could be built up quicker. These Neotropical primates have placentas that differ in several ways from human placenta.

Haematopoietic foci in the placenta of a marmoset

(Callithrix jacchus) from Carter and Mess (here)

© Museum für Naturkunde Berlin

As an example, the placenta is an important site of haematopoiesis. The conventional wisdom is that there is little or no trophoblast invasion, but this is one aspect that calls for reexamination. If marmosets begin to emerge as important disease models there will be a need to look more closely at their placentation.

Denisovans crossed the Wallace line

Wallacea is bordered to the west by the Wallace Line

and to the east by the Lydekker Line (Wikimedia Commons)

Denisovans were archaic hominins distinct from Neanderthals and modern humans (previous post). There is evidence for gene flow between all three populations and putatively a fourth. The greatest amount of introgressed Denisovan DNA is found in the aboriginal peoples of New Guinea and Australia (here).

This is remarkable for several reasons. Firstly, it is a long way from Denisova in Siberia to New Guinea. Secondly, there is no trace of Denisovan DNA in modern humans from mainland Asia or from Southeast Asia west of the Wallace Line. As pointed out in a recent essay (here), the most likely explanation is that Denisovans crossed the Wallace Line into Wallacea (see map) and that exchange of genes with modern humans occurred there. Traces of Denisovan DNA do occur in modern populations from Wallacea as well as further east to Polynesia and Fiji.

Does that mean there was no contact between Denisovans and the ancestors of present day Asian populations? Not necessarily. Some Denisovan genes may have been retained east of the Wallace Line because they conferred resistance to disease (purifying selection). Further west Denisovan DNA may have been "overwritten" in the course of time.   

Do not marsupials have trophoblast?

Embryonic and trophoblastic areas of the marsupial

blastocyst as envisaged by Hartman 

In the final chapter of her book (previous post), Zofia Kielan-Jaworowska writes on placental mammals, "Their enormous success depends in the first place on the acquisition of the trophoblast, on the basis of which the placenta is formed." In contrast, "Without the trophoblast, marsupials are unable to prolong their gestation period and are born at an extremely early level of anatomical development." This view or a version of it seems to be shared by other zoologists. 

The souce of the misunderstanding can be traced to influential papers by Jason A. Lillegraven (e.g. here). The marsupial blastocyst lacks the inner cell mass of a placental mammal blastocyst. Early on, however, there are two distinct areas that often have been referred to as the embryonic and trophoblastic areas. Lillegraven argues, convincingly in my view, that the "embryonic area" is not equivalent to the inner cell mass and that a considerable portion of the "trophoblastic area" forms part of the developing embryo. In an anatomical sense the trophoblastic area is not the trophoblast as defined by Hubrecht (see previous post).

Nonetheless, Lillegraven also says, "But from a functional point of view (as applied to extra-embryonic parts of the conceptus having direct nutritive significance), the term "trophoblast" may be used to good advantage throughout the Amniota, whether development occurs within a shelled or a shell-free setting."

Thus marsupials do have trophoblast and of course they all have at least a yolk sac placenta and sometimes a chorioallantoic placenta to boot. As shown by Ulrich Zeller and Claudia Freyer (here) there are marsupials where the trophoblast forms  a syncytium and exhibits invasive properties.

As noted in a previous post, there are sound reasons for distinguishing between Eutheria and Placentalia but it is little wonder that marsupial specialists bridle at the term "placental mammals."  

Karl Bogislaus Reichert

Karl Bogislaus Reichert (1811-1883)

Crucial to our understanding of the evolution of mammals is the origin of the bones of the inner ear from what were elements of the jaw articulation in reptiles. This was worked out in 1837 by the German embryologist Karl Bogislaus Reichert. Zofia Kielan-Jaworowska (previous post) notes this is all the more remarkable in view of the primitive tools available at the time. Later Ernst Gaupp built on this work and the supposed origin of the inner ear bones is known as the Reichert-Gaupp theory.



Reichert's membrane (Rm) in the placenta of the capybara

From Kanashiro et al. Reprod Biol Endocrinol 2009; 7: 57 (here)

Students of the placenta will be more familiar with the name of Reichert through the eponymous membrane that lies between the trophoblast and the endoderm of the parietal yolk sac in rodents and insectivores. It was first described by Reichert in the guinea pig (Abh Akad Wissensch Berlin 1862; pp. 97-216).

In pursuit of early mammals

A multituberculate (Catopsbaatar) about to fall prey

to a dinosaur (Saurornithoides)

This fascinating book is the autobiography of the eminent paleontologist Zofia Kielan-Jaworowska and an introduction to the early history of mammals.

Her descriptions of the Polish-Mongolian expeditions in 1963-71 recount the daunting logistics of working in the Gobi Desert 1000 km from Ulaanbaatar and transporting back fossils weighing several tons. The excitement of the fossil hunt is apparent: "I turned the block over and was left speechless! I had in my hands an almost complete, beautifully preserved skull of a small dinosaur." With this as a starting point we follow Zofia Kielan-Jaworowska's subsequent career, which included eight years on the faculty of Oslo University. In 2002 she returned to Gobi with her grandaughter Zosia; ten years on Zosia checked the references for the current volume. 

The second half of the book focuses on the evolution of mammals. It is restricted to the crown group that includes the living monotremes, marsupials and placentals and extinct groups with which they share a common ancestor. Arguably this includes the fossils of greatest interest to the general reader. For a more comprehensive treatment of the subject there is Mammals from the Age of Dinosaurs (2004) by Kielan-Jaworowska, Cifelli and Luo.

The new book contains potted biographies of many eminent vertebrate paleontologists, including some of the author's predecessors as well as recent stars such as Zhe-Xi Luo. It is richly illustrated with historical photos and line drawings of fossil mammals from the age of dinosaurs.

The spiny mouse

Spiny mouse (Acomys sp.) Wikimedia Commons

Despite its appearance the spiny mouse belongs to a different subfamily than the laboratory mouse. More importantly, it has a different reproductive strategy. Litter size is smaller and much of organ development occurs in utero resulting in the birth of precocial young. Thus it is a better model for late gestation in humans than the mouse, which has large litters and altricial young (see previous post).

At the same time, the laboratory species (Acomys cahirinus) is sufficiently close to mouse and rat that it is possible to develop primers based on the nucleotide sequences of mouse and rat genes (exemplified here). 

A group at Monash University has been using the spiny mouse in studies of fetal programming and sex-dependent effects of glucocorticoids on placental development (here). The spiny mouse holds great promise as a new model for placental and fetal development. Moreover, its potential for studies in a quite different area, tissue regeneration (here), means it is likely to be come more widely available as a laboratory animal.

Maureen Young 1915-2013



Maureen Young in Denmark 1989

Professor I. Maureen Young made an important contribution to our knowledge of amino acid transfer across the placenta and its role in fetal nutrition.

Maureen Young graduated from Bedford College for Women in 1938 and continued there as a demonstrator and assistant lecturer. During the Second World War the College evacuated to Cambridge where Maureen met Sir Joseph Barcroft. This was the start of a life long interest in fetal physiology (see her review of Barcroft's book here). In 1946 she moved to St. Thomas's Hospital Medical School. She was Professor of Perinatal Physiology there from 1976 until her retirement in 1982. She then settled at Toft in Cambridge.

Maureen was one of a generation of women who rose to the top in research often at great personal sacrifice. She wrote about some of the others in Women Physiologists (Portland Press 1993). At placenta meetings she was often to be found in the company of her American counterpart Elizabeth M. Ramsey (previous post).

Although international travel was eventually curtailed, Maureen continued to attend scientific meetings at Cambridge until well into her 95th year. She will be greatly missed. 

An ancient endogenous retrovirus

Classes of ERVs Wikimedia Commons

Endogenous retroviruses (ERVs) are genes of retroviral origin that have been incorporated into the genome. They include the syncytins expressed in the placentas of various mammals. Six are known so far and each represents a separate capture of a retroviral gene (see previous post). 

Now an ERV has been described that occurs in representatives of all four superordinal clades of placental mammal (here). In this case the gene is orthologous and thus represents a single integration event that must have predated the divergence of placental mammals in the Cretaceous (for possible dates see my recent post).

This work was published in a special issue of Phil Trans R Soc B on the theme "Paleovirology: insights from the genomic fossil record." Although sequence substitutions occur over time, an ERV is essentially a "fossil" record of a virus as it existed at the time of incorporation into the host genome. Thus the study of ERVs in various organisms (not just mammals) can provide insight into the long term history of viruses and virus-host interactions (see overview here).

In a historical overview of the field (here) Robin A. Weiss notes, "The advantage to the host of ERV protein expression is most dramatic in the evolution of the mammalian placenta." Incidentally, if you find the whole concept hard to swallow you are in good company as the early history of the field so clearly shows.

The Mammalian Ovary

Mossman and Duke 1973

It is now 40 years since publication of Harland Mossman's "other" book (previous post). It differs in many respects from the better known volume on fetal membranes. In particular it is richly illustrated with photomicrographs. Most of the specimens were in the collections of its authors. The Harland W. Mossman Collection is conserved at the University of Wisconsin Zoological Museum and there is a searchable data base (here).

Kenneth L. Duke was an alumnus of Brigham Young University at Provo, Utah. On retiring from Duke University he sent his collection there. Mercifully it has remained intact although it has not been catalogued. Much of the material will be from Duke's yearly field trips to The Great Basin but there is also material from South East Asia. There are placentas from some species including the Philippine colugo.

Comparative Morphology of the Mammalian Ovary takes as a starting point the red squirrel (Tamiasciurus hudsonicus) before dealing with a number of topics across the full range of mammals. For individual taxa the synoptic tables at the back of the book are unsurpassed as a source. The footnotes to these tables indicate where they rely on Duke's Collection now at BYU.

Disclosure: I am adjunct curator of The Harland W. Mossman Collection.    

Alternative views on the origin of placentals

The first placental mammal

From O'Leary et al. Science 2013; 339: 662-7

Reprinted with permission from AAAS

Hot on the heels of the controversy about crown mammals comes a dust up over crown placentals. This time in Science and in response to an important paper by O'Leary et al. that combined morphological and molecular data (see previous post). One conclusion in that paper (here) was that ordinal diversification of placentals occurred after the Cretaceous-Paleogene boundary (Explosive Model, cf. Wednesday's post).

This has elicited a response from an eminent group of molecular phylogeneticists (Springer et al. here). Their best estimate of the origin of placentals (here) posits a common ancestor 100 Mya with most orders arising in the Cretaceous (Long Fuse Model). They contend that that molecular phylogenies are more reliable than phenome-based (morphological) phylogenies even when they imply ghost lineages (i.e. with no fossil record).

In their rebuttal, O'Leary et al. (here) note that molecular phylogenetics has failed to resolve the basal split in Placentalia (see here) or to establish a sister taxon for primates. Thousands of nonplacental Cretaceous fossils are known so why are placentals absent? 

A seemingly weightier point made by Springer et al. is that ordinal diversification over a short time span in the early Paleocene implies high substitution rates. Maybe so respond O'Leary et al. Let's redo our tree but impose average substitution rates as a limitation. The result is to extend the origin of orders past the K-Pg boundary but only by some 6 My. That puts the common ancestor at 70 Mya which is still 30 My later than the molecular estimate.

New fossils support alternative views of mammalian evolution

Alternative interpretations of early mammalian history

Reproduced with permission by Macmillan Publisher Ltd.

from Cifelli and Davis (here) copyright 2013

Crown Mammalia are the extant monotremes, marsupials and placentals together with all extinct species with which they share a common ancestor. It is widely accepted that they include the multituberculates that became extinct in the Oligocene.

Two well preserved Jurassic fossils from another group of mammaliforms, the haramiyids, are described in the current issue of Nature. In one paper (here) the fossil form (Arboroharamiya jenkinsi) is found to group with the multituberculates and thus within Crown Mammalia. Since the haramyids have a deep fossil record this pushes the common ancestor of crown mammals back into the Late Triassic.

The second analysis (here) of a different fossil (Megaconus mammaliaformis) places haramiyids outside crown placentals, which thus can retain a Jurassic origin.

An accompanying commentary (here) notes that a Triassic origin is in accordance with the "long fuse" hypothesis of mammalian evolution whereas a Jurassic origin better corresponds to the "explosive" hypothesis. These authors tend to favour the conclusion based on Megaconus as it is a more complete fossil and the counterparts of the middle ear bones remain attached to the mandible, differing in this respect from extant mammals and multituberculates.

Placentation in colugos

Colugo fetus near term from Hubrecht (1919)

Colugos (once known as flying lemurs) are of interest because of their close relationship to primates. Dermoptera (colugos), Scandentia (tree shrews) and Primates group together as Euarchonta.

Dilated maternal blood spaces in a colugo placenta

Hill Collection micrograph courtesy of Allen C. Enders

Their placentation is of interest because it seems to be intermediate between a labyrinthine and villous form. Starck referred to it as a Zwischenform and Wislocki compared it to the trabecular placenta of Neotropical primates. This not withstanding, we still lack a complete description of the term placenta. Mossman (previous post) could not reconcile his own observations with unpublished drawings by Luckett and urged further study. 

Hubrecht (previous post) accumulated 182 uteri of the Sunda colugo (Galeopterus variegatus). His thorough description of early fetal development, published posthumously (Verhandelingen der Koninklijke Akademie van Wetenschappen 1919), stopped at the establishment of the definitive placenta. J. P. Hill collected specimens of the Sunda colugo and the Philippine colugo (Cynocephalus volans) but did not describe them. Nor did Amoroso (previous post) who apparently borrowed most of Hill's slides. The time is ripe for a thorough study of colugo placentation.

Exosomes

Endosomal pathways from Danzer et al. (here) © 2012 Danzer et al.

Exosomes are tiny vesicles (50-100 nm) released from living cells. They represent a hitherto overlooked route of intercellular communication. Exosomes were the focus of a symposium at the CTR Annual Meeting at Cambridge earlier this month.

The precursors to exosomes are intralumenal vesicles (ILVs), which are found in multivesicular bodies (MVBs) or "late endosomes." ILVs are formed by invagination of the outer membrane of the MVB. Thus initially they contain cytosol. However, the ILV outer membrane can be restructured by a scramblase and both proteins and lipids can be sorted into the ILVs before they are released as exosomes. Recently the focus has been on the direction of microRNAs into exosomes. The argument convincingly presented at Cambridge was that exosomes once released act as carriers to take proteins, lipids and RNAs to target cells. Their contents are released to the target cell following fusion of the exosome with its plasma membrane or uptake of the complete exosome. One of the speakers at Cambridge was Michel Record whose previous review (here) can be recommended. 

Multivesicular bodies are a prominent feature of the guinea placenta (here). They are associated with a system capable of taking up maternal proteins and transporting them to the fetal circulation. The potential role of exosomes in this context deserves to be explored. Could they be involved in the transfer of intact maternal antibodies that confers passive immunity on the fetus?

Amo's chapter on placentation

Amo Cambridge 1972

Emmanuel Ciprian Amoroso FRS (Amo) is best remembered for his monumental chapter on Placentation written for the 1952 edition of Marshall's Physiology of Reproduction edited by A. S. Parkes (Volume II pages 127-309).

Amo was born in Trinidad and graduated in medicine from the National University of Ireland. He then spent 1930-32 in Germany and his knowledge of the German literature (almost unread in the English speaking world) was one reason his chapter was so important.

Amo then came to University College London where he completed his Ph.D. under the auspices of J. P. Hill. From there he moved to the Royal Veterinary College where he was Professor of Veterinary Physiology from 1950 to his retirement in 1968. Amo was a mentor for many scientists with distinguished careers. He continued in this role on retirement when he found a new home at the Institute of Animal Physiology at Babraham near Cambridge. He died in 1982.

An engaging account of Amo's life was written by R. V. Short (here). The true monument remains his chapter which has a place of honour on my bookshelf.

How large were the first placentals?

Dinosaurs and insectivores

Colbert (1955) Evolution of the Vertebrates

Were the first placentals (mammals other than marsupials and monotremes) tiny animals living in the shadow of the dinosaurs? The idea predates cladistics and molecular phylogenetics (see above). Most fossils from the Mesozoic are indeed small.

A recent study (here) took another approach based on the fact that there is a faster divergence in GC3 in long-lived species than in short-lived ones (GC3 is the percentage of guanine and cytosine at the third position of gene codons). Body size correlates to longevity.

The authors constructed a tree based on the genomes of 33 placentals with two marsupials and a monotreme as outgroups. They then estimated the ancestral GC3 at each node of the tree including the most recent common ancestor of placentals. From this last value they could estimate the longevity and body mass of early placentals. The surprising result was they had a life span above 25 years and a body mass above 1 kg (less if arboreal).

Looking at mammals as a whole (not just eutherians/placentals and metatherians/marsupials), the fossil record offers several examples of medium to large mammals such as Sinocondon from the Jurassic and Repenomamus from the Early Cretaceous (elegantly reviewed by Luo here). It is not beyond the bounds of possibility that the most recent common ancestor of placentals was in a similar size range.

Ossification patterns and the phylogeny of mammals

Afrotherian embryos. Reproduced from Hautier et al. (here)

© 2013 The Authors

High resolution X-ray microtomography is among new methods available to comparative anatomists. It enables non-invasive imaging of museum specimens and subsequent 3D visualisation of the tissues. One field where it has been applied is to study the sequence in which bones become ossified during embryonic and fetal development.

An obvious requirement is that developmental series are available as for the African elephant (here) and tail-less tenrec (here). A new study from the Department of Zoology at Cambridge (here) analyzes data from a wider range of afrotherians. It then compares ossification patterns in "southern" mammals (Afrotheria and Xenarthra) and "northern" mammals (Laurasiatheria  and Euarchontoglires).

The "northern" mammals share a common ancestor (together constituting Boreoeutheria). There is little variability in developmental sequences between species available for study. In contrast both groups of "southern" mammals exhibit shifts in ossification sequences. At first sight this might seem to argue for a common ancestor for Afrotheria and Xenarthra. However, the shifts are different in the two clades and this could argue against a common ancestry.

The data are intriguing as we still lack certainty about the root of the tree. This is largely because the four major clades diverged so rapidly early in the history of placental mammals. Even phylogenomics has yielded conflicting results (discussed here).

Placentation in the koala

Koala (Phascolarctos cinereus) 

Photo by David Iliff. License: CC-BY-SA 3.0

The koala (Phascolarctos cinereus) is a member of Vombatidae and its fetal membranes resemble those of the wombats (previous post).

Fetal membranes of the koala from Caldwell (1884)

In fact adherence of the allantois to the chorion was first described for this marsupial (here). Richard Semon soon suggested that this combination of yolk sac and simple chorioallantoic placentation was present in the common ancestor of marsupials and placentals. In other marsupials the chorioallantoic placenta was lost (bandicoot placentation had not then been described); in placentals the chorioallantoic placenta was elaborated and the yolk sac reduced or lost. In recent times this idea was revived by Freyer, Zeller and Renfree (here).

There is little of recent date though the koala is included in a review by Hughes (here) as well as a later book chapter. Based in part on the Hill Collection it includes histology of the yolk sac placenta and gross morphology of the chorioallantoic placenta.

Updated 17 July 2013

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).

How wombats do it

Rossetti lamenting the death of his wombat

Wombat husbandry has improved since Rossetti's time, but wombats are still difficult to breed in captivity.The northern hairy-nosed wombat Lasiorhinus krefftii is among the rarest species of mammal and a captive breeding program might be needed to save it from extinction. A timely review (here) summarizes what we know and still need to learn about wombat reproduction.

Fetal membranes of the long-nosed bandicoot Perameles

nasuta from Hill (1897) redrawn by Amoroso

Wombats and their close relative the koala Phascolarctos cinereus have a chorioallantoic placenta as well as the yolk sac placenta characteristic of marsupials (previous post). In this respect they resemble the bandicoots. J. P. Hill described placentation in the Southern brown bandicoot in 1895 and two years later published a detailed description for the long-nosed bandicoot (here). As wombats and bandicots are not closely related, this might be an instance of convergent evolution. Although it has also been argued (here) that a chorioallantoic placenta was present in the common ancestor of marsupials and lost in the remaining lineages.

Our knowledge of placentation in wombats relies on specimens of Vombatus ursinus collected by Hill in 1899-1901 and conserved as part of The Hubrecht Collection at Museum für Naturkunde in Berlin. These specimens have been described by Hughes and Green (In: Wells RT, Pridmore PA Wombats Chipping Norton NSW: Surrey Beatty & Sons, 1998).

An aquatic past for elephants

Endotheliochorial placenta of the Amazonian manatee

Fetal (fc) and maternal (mc) capillaries are present

The closest relatives to elephants are the dugong and manatees. Placentation in the African elephant Loxodonta africana has been well studied (reviewed here). We were able to show strong resemblances in the placenta and fetal membranes between the elephant and the Amazonian manatee Trichecus inunguis (here).

This hoax photo of the Loch Ness monster

is thought to be an elephant swimming

It has long been suspected that the ancestor of proboscideans was aquatic or semi-aquatic (here). Clues include the presence of nephrostomes in the mesonephros of the fetus (here). Now support comes from an unexpected quarter: myoglobin.

Diving mammals such as whales and seals have high amounts of myoglobin in their muscles to act as a source of oxygen during prolonged submersion. A new study (here) shows that in such species there is an increase in surface charge of the molecule to prevent dimerization occurring at high concentrations of myoglobin. This molecular signature was also found in sirenians and proboscideans. The analysis included two extinct species: the woolly mammoth (previous post) and Steller's sea cow. A phylogenetic analysis suggested that substitutions contributing to increased surface charge on myoglobin occurred in the common ancestor of sea cows, elephants and hyraxes (paenungulates). The conclusion drawn is that this ancestor may have been semiaquatic.

How we do it

The subtitle of this new book is The Evolution and Future of Human Reproduction. Nobody is better qualified to discuss that than Bob Martin, an anthropologist based at Chicago's Field Museum. Although written for a general audience, there is no attempt to dumb down the material.

Human reproduction has many unique features even in relation to other primates and this book provides a comprehensive overview and the necessary evolutionary context. It is useful background for scientists who might be steeped in particular aspects (such as placentation) but not in others (menstruation or lactation). For readers stimulated to explore further there are excellent scientific reviews by the same author (e.g. here and here). 

Embryos and ancestors in deep time

I read Gavin de Beer's monograph while still at school. Scornful of Haeckel's idea that ontogeny recapitulates phylogeny, de Beer details the several ways in which embryonic development is modified during the evolution of new species. The book remains a useful reference source for concepts like neotony and paedomorphosis.

Fifty years on, I was delighted to read this new monograph by Marcelo Sánchez-Villagra. He is a paleontologist and gives fascinating examples from the fossil record. Developmental series of extinct species are relatively rare, but much can be induced from studies of bone and tooth structure. Modern and non-invasive imaging techniques are able to yield new information from rare specimens diligently guarded by museum curators. Phylogenetic bracketing (as of non-avian dinosaurs between crocodiles and birds) is another approach from which we can infer developmental processes in extinct lineages. It then becomes possible to speculate on the role of the Hox family of regulatory genes and draw on other data from molecular biology.

There is of course much here on the evolution of viviparity and placentation and on reproductive strategies. The fossil record has much to teach us here (see my paper here).

De Beer was scathing about Haeckel because his ideas had stood in the way of experimental embryology. Sánchez is kinder, recalling that more Europeans learned about evolution from the writings of Haeckel than of Darwin. His own view is summed up as "ontogeny does not usually recapitulate phylogeny."

The focus of this book is sharpest in the opening chapters and I would have liked to have seen the threads drawn together in a concluding chapter. It is nonetheless a good read and never gets bogged down in technicalities.

The primrose way

Space-filling model of the hydrogen sulfide molecule (Ben Mills)

Hydrogen sulfide (H₂S) is a signaling molecule in the brain and cardiovascular system. The antihypertensive effect of garlic has been attributed to the generation of H₂S from its contained polysulphides (reviewed here).

A recent study (here) indicates that H₂S may play a role in regulating blood flow on the fetal side of human placenta. One of the enzymes that generates H₂S (CSE) is found in the smooth muscle layer of stem villus arteries. Moreover it was shown using the H₂S donor NaHS that the molecule is able to dilate the fetal placental circulation. Because the placenta lacks innervation, signaling molecules like H₂S are likely to be important in the regulation of blood flow. The study found evidence that CSE expression is decreased in pathological pregnancies such as preeclampsia and fetal growth restriction.

H₂S is involved in oxygen sensing in the carotid body (here) and one wonders if it might perform a similar role in the placenta.

The origin of apes



The Rift Valley Kenya (Wikimedia Commons)

Trees based on molecular data often predict divergence points at odds with the fossil record. Thus the divergence between Old World monkeys (Cercopithecoidea) and apes (Hominoidea) has been dated to 25-30 Mya, implying a long ghost lineage for both superfamilies. New fossils from the East African Rift have now closed the gap (here). One (Nsungwepithecus gunnelli) is a cercopithecoid. The other (Rukwapithecus fleaglei) shares dental features with Miocene and extant hominoids that are not present in cercopithecoids.

Pregnant uterus of Hylobates agilis (rafflei) showing the decidua

capsularis (d.c.) reproduced by Hill (here) from Selenka

Implantation is superficial in Old World monkeys, whereas interstitial implantation occurs in all living apes including gibbons. This was shown more than a century ago by Emil Selenka. The illustration above is of Hylobates rafflei named in honour of Stamford Raffles (previous post) but now subsumed in H. agilis.

Trophoblast invasion by the interstitial route occurs neither in Old World monkeys nor in gibbons so post dates the origin of apes. This key feature of human placentation is shared by gorilla and chimpanzee (discussed here). No information is available for orang utan.

Placentation in the Laotian rock rat

The Laotian rock rat Laonastes aenigmamus
From Nicolas et al. 2012 (here)

Discovered in 1997, this rodent belongs to the family Diatomyidae that was thought to have died out in the late Miocene (background here). Molecular data place it basal to hystricognath rodents such as the guinea pig and capybara.

Cross section through the rock rat uterus, placenta and fetal membranes

Reproduced from Carter et al. © (2013) with permission from Elsevier 

The internal structure of the placenta was rather simple with a separate labyrinth and spongy zone. In contrast, the hystricognath placenta is highly folded with lobules of labyrinth separated by interlobular areas of spongiotrophoblast.

Thin section through the exchange area of a rock rat placenta

Reproduced from Carter et al. © (2013) with permission from Elsevier 

The interhemal barrier was hemodichorial, i.e. with two trophoblast layers. The maternal blood spaces (mbs) were lined by syncytiotrophoblast (syn tr) and below this was a layer of cytotrophoblast (ctr). This pattern is different from all other rodents that have been studied so far.

Some distinctive features of hystricognath placentation, such as the subplacenta, were not found in the Laotian rock rat. On the other hand this species does resemble hystricognaths in giving birth to a single precocial pup.

Disclosure: I am lead author of this paper and must acknowledge my colleagues Jean-Pierre Hugot (Paris), Allen C. Enders (Davis), Carolyn J. P. Jones (Manchester) and Par Kham Keovichit (Vientine).

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.

Elizabeth Maplesden Ramsey

Elizabeth Ramsey lecturing at Rotterdam in 1980

A legend in her lifetime Elizabeth Ramsey was always kind to young investigators and an inspiration to women scientists. She wrote a slim volume on The Placenta of Laboratory Animals and Man that offers valuable insight into the realm of comparative placentation. 

Twenty years have passed since her death. As a researcher Elizabeth is best remembered for two things. At the very start of her career as a pathologist she discovered a very early human implantation site, the Yale embryo. This marked the start of her affiliation with the Carnegie Institution of Washington from 1934 until well beyond her retirement.

Corrosion cast of vessels in a rhesus monkey placenta. Maternal spiral artery red and fetal vessels white. The handwriting is Elizabeth Ramsey's

Second she studied the maternal placental circulation in the rhesus monkey and other primates beginning with 3D wax reconstructions of the blood vessels and proceeding through corrosion casts (above) to visualization of the blood flow by cineradioangiography. An appreciation of this work in its historical context has been written by Larry D. Longo and Giacomo Meschia (here).

My personal debt to Elizabeth dates back half a century when I was an undergraduate. In reply to my letter she sent many words of encouragement and reprints of her papers. It was typical of her generosity.