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When and why did variations in placental structure and function evolve? Such questions cannot be addressed without a reliable version of mammalian phylogeny. Twenty-five years ago, the mammalian tree was reshaped by molecular phylogenetics. Soon it was shown, in contrast to prevailing theories, that the common ancestor of placental mammals had invasive placentation. Subsequently, evolution of many other features of extraembryonic membranes was addressed. This endeavour stimulated research to fill gaps in our knowledge of placental morphology. Last year the mammalian tree was again revised based on a large set of genomic data. With that in mind, this review provides an update on placentation in the nineteen orders of placental mammals, incorporating much recent data. The principal features such as shape, interdigitation, the interhaemal barrier and the yolk sac are summarized in synoptic tables. The evolution of placental traits and its timing is then explored by reference to the revised mammalian tree. Examples are the early appearance of epitheliochorial placentation in the common ancestor of artiodactyls, perissodactyls, pangolins and carnivores (with reversion to invasive forms in the latter) and later refinements such as the binucleate trophoblast cells and placentomes of ruminants. In primates, the intervillous space gradually evolved from the more basic labyrinth whereas trophoblast invasion of the decidua was a late development in humans and great apes. Only seldom can we glimpse the "why" of placental evolution. The best examples concern placental hormones, including some striking examples of convergent evolution such as the chorionic gonadotropins of primates and equids. In concluding, I review current ideas about what drives placental evolution and identify significant gaps in our knowledge of placentation, including several relevant to the evolution of placentation in primates. [Display omitted] • Placental evolution in mammals is interpreted from the newly revised phylogenomic tree. • Traits with a deep origin include the four-chambered allantoic sac of afrotherians • Traits with a late origin include the intervillous space of haplorrhine primates. • Some morphological traits can be linked to hormone secretion in ruminants, horses, rodents and primates. [ABSTRACT FROM AUTHOR]

Abstract Background Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey information to conspecifics by secreting a pallet of small volatile molecules produced by symbiotic bacteria. Because these glands are unique to carnivores, it is unclear how their secretions relate to those of other placental mammals that make use of different tissues and secretions for chemical communication. Here we analyse the anal sac glands of domestic dogs to verify the secretion of proteins and infer their evolutionary relationship to those involved in the chemical communication of non-carnivoran mammals. Results Proteomic analysis of anal sac gland secretions of 17 dogs revealed the consistently abundant presence of three related proteins. Homology searches against online databases indicate that these proteins are evolutionary related to ‘odorant binding proteins’ (OBPs) found in a wide range of mammalian secretions and known to contribute to chemical communication. Screening of the dog’s genome sequence show that the newly discovered OBPs are encoded by a single cluster of three genes in the pseudoautosomal region of the X-chromosome. Comparative genomic screening indicates that the same locus is shared by a wide range of placental mammals and that it originated at least before the radiation of extant placental orders. Phylogenetic analyses suggest a dynamic evolution of gene duplication and loss, resulting in large gene clusters in some placental taxa and recurrent loss of this locus in others. The homology of OBPs in canid anal sac glands and those found in other mammalian secretions implies that these proteins maintained a function in chemical communication throughout mammalian evolutionary history by multiple shifts in expression between secretory tissues involved in signal release and nasal mucosa involved in signal reception. Conclusions Our study elucidates a poorly understood part of the biology of a species that lives in close association with humans. In addition, it shows that the protein repertoire underlying chemical communication in mammals is more evolutionarily stable than the variation of involved glands and tissues would suggest.

The punctuated mode of evolution posits that evolution occurs in rare bursts of rapid evolutionary change followed by long periods of genetic stability (stasis). The accepted cause for the rapid changes in punctuated evolution is special ecological circumstances – selection forces brought about by changes in the environment. This article presents a complementary explanation for punctuated evolution by the rapid formation of genetic variants in animals and plants by the acquisition of microorganisms from the environment into microbiomes and microbial genes into host genomes by horizontal gene transfer. Several examples of major evolutionary events driven by microorganisms are discussed, including the formation of the first eukaryotic cell, the ability of some animals to digest cellulose and other plant cell-wall complex polysaccharides, dynamics of root system architecture, and the formation of placental mammals. These changes by cooperation were quantum leaps in the evolutionary development of complex bilolgical systems and can contribute to an understanding of the mechanisms underlying punctuated evolution.

Abstract Background Besnoitia darlingi, B. neotomofelis and B. oryctofelisi are closely related coccidian parasites with felids as definitive hosts. These parasites use a variety of animal species as intermediate hosts. North American opossums (Didelphis virginiana), North American southern plains woodrats (Neotoma micropus) and South American domestic rabbits (Oryctolagus cuniculus) are intermediate hosts of B. darlingi, B. neotomofelis and B. oryctofelisi, respectively. Based on conserved regions in the internal transcribed spacer-1 (ITS1) sequence of the ribosomal DNA (rDNA), a real-time PCR for a sensitive detection of these Besnoitia spp. in tissues of intermediate hosts and faeces of definitive hosts has recently been established. Available sequence data suggest that species such as B. akodoni and B. jellisoni are also covered by this real-time PCR. It has been hypothesised that additional Besnoitia spp. exist worldwide that are closely related to B. darlingi or B. darlingi-like parasites (B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni). Also related, but not as closely, is B. besnoiti, the cause of bovine besnoitiosis. Methods Faecal samples from two free-ranging cheetahs (Acinonyx jubatus) from Namibia that had previously tested positive for coccidian parasites by coproscopy were used for this study. A conventional PCR verified the presence of coccidian parasite DNA. To clarify the identity of these coccidia, the faecal DNA samples were further characterised by species-specific PCRs and Sanger sequencing. Results One of the samples tested positive for B. darlingi or B. darlingi-like parasites by real-time PCR, while no other coccidian parasites, including Toxoplasma gondii, Hammondia hammondi, H. heydorni, B. besnoiti and Neospora caninum, were detected in the two samples. The rDNA of the B. darlingi-like parasite was amplified and partially sequenced. Comparison with existing sequences in GenBank revealed a close relationship to other Besnoitia spp., but also showed clear divergences. Conclusions Our results suggest that a so far unknown Besnoitia species exists in Namibian wildlife, which is closely related to B. darlingi, B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni. The cheetah appears to be the definitive host of this newly discovered parasite, while prey species of the cheetah may act as intermediate hosts.

Abstract Background One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. Results Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. Conclusions We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.

Background: Besnoitia darlingi, B. neotomofelis and B. oryctofelisi are closely related coccidian parasites with felids as definitive hosts. These parasites use a variety of animal species as intermediate hosts. North American opossums (Didelphis virginiana), North American southern plains woodrats (Neotoma micropus) and South American domestic rabbits (Oryctolagus cuniculus) are intermediate hosts of B. darlingi, B. neotomofelis and B. oryctofelisi, respectively. Based on conserved regions in the internal transcribed spacer-1 (ITS1) sequence of the ribosomal DNA (rDNA), a real-time PCR for a sensitive detection of these Besnoitia spp. in tissues of intermediate hosts and faeces of definitive hosts has recently been established. Available sequence data suggest that species such as B. akodoni and B. jellisoni are also covered by this real-time PCR. It has been hypothesised that additional Besnoitia spp. exist worldwide that are closely related to B. darlingi or B. darlingi-like parasites (B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni). Also related, but not as closely, is B. besnoiti, the cause of bovine besnoitiosis. Methods: Faecal samples from two free-ranging cheetahs (Acinonyx jubatus) from Namibia that had previously tested positive for coccidian parasites by coproscopy were used for this study. A conventional PCR verified the presence of coccidian parasite DNA. To clarify the identity of these coccidia, the faecal DNA samples were further characterised by species-specific PCRs and Sanger sequencing. Results: One of the samples tested positive for B. darlingi or B. darlingi-like parasites by real-time PCR, while no other coccidian parasites, including Toxoplasma gondii, Hammondia hammondi, H. heydorni, B. besnoiti and Neospora caninum, were detected in the two samples. The rDNA of the B. darlingi-like parasite was amplified and partially sequenced. Comparison with existing sequences in GenBank revealed a close relationship to other Besnoitia spp., but also showed clear divergences. Conclusions: Our results suggest that a so far unknown Besnoitia species exists in Namibian wildlife, which is closely related to B. darlingi, B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni. The cheetah appears to be the definitive host of this newly discovered parasite, while prey species of the cheetah may act as intermediate hosts. [ABSTRACT FROM AUTHOR]

Introduction: The chorioallantoic placenta is a specific organ for placental mammals. However, the adaptive events during its emergence are still poorly investigated.Methods: We scanned the chromosome X to detect the accelerated evolution in the ancestral lineage of placental mammals, and constructed 3D protein structure models of a candidate by homology modeling.Results: Eight branch-specific accelerated regions were identified. Five of these regions (P=5.61×10-11 ~ 9.03×10-8) are located in the five exons of Nik-related kinase (Nrk), which is essential in placenta development and fetoplacental induction of labor. Nrk belongs to the germinal center kinase-IV subfamily with the overall similar protein structure; however, a new exon emerged in ancestors of placental mammals and its sequence has been conserved since then. Structure modelling of NRK suggests that the accelerated exons and the placental-mammal-specific exon (as a new loop) could change the enzymatic activity and the structure of placental mammal NRK.Discussion: Since the new loop is surrounded by the accelerated protein regions, it is likely that the new loop occurred and shifted the function of NRK, and then the accelerated evolution of Nrk occurred to adapt the structure change caused by the new loop in the ancestral lineage of placental mammals. Overall, this work suggests that the fundamental process of placental development and fetoplacental induction of labor has been targeted by positive Darwinian selection. [ABSTRACT FROM AUTHOR]

Background: Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey information to conspecifcs by secreting a pallet of small volatile molecules produced by symbiotic bacteria. Because these glands are unique to carnivores, it is unclear how their secretions relate to those of other placental mammals that make use of diferent tissues and secretions for chemical communication. Here we analyse the anal sac glands of domestic dogs to verify the secretion of proteins and infer their evolutionary relationship to those involved in the chemical communication of non-carnivoran mammals. Results: Proteomic analysis of anal sac gland secretions of 17 dogs revealed the consistently abundant presence of three related proteins. Homology searches against online databases indicate that these proteins are evolutionary related to 'odorant binding proteins' (OBPs) found in a wide range of mammalian secretions and known to contribute to chemical communication. Screening of the dog's genome sequence show that the newly discovered OBPs are encoded by a single cluster of three genes in the pseudoautosomal region of the X-chromosome. Comparative genomic screening indicates that the same locus is shared by a wide range of placental mammals and that it originated at least before the radiation of extant placental orders. Phylogenetic analyses suggest a dynamic evolution of gene duplication and loss, resulting in large gene clusters in some placental taxa and recurrent loss of this locus in others. The homology of OBPs in canid anal sac glands and those found in other mammalian secretions implies that these proteins maintained a function in chemical communication throughout mammalian evolutionary history by multiple shifts in expression between secretory tissues involved in signal release and nasal mucosa involved in signal reception. Conclusions: Our study elucidates a poorly understood part of the biology of a species that lives in close association with humans. In addition, it shows that the protein repertoire underlying chemical communication in mammals is more evolutionarily stable than the variation of involved glands and tissues would suggest. [ABSTRACT FROM AUTHOR]

Immunoglobulins and T cell receptors (TCR) have obvious structural similarities as well as similar immunogenetic diversification and selection mechanisms. Nevertheless, the two receptor systems and the loci that encode them are distinct in humans and classical murine models, and the gene segments comprising each repertoire are mutually exclusive. Additionally, while both B and T cells employ recombination-activating genes (RAG) for primary diversification, immunoglobulins are afforded a supplementary set of activation-induced cytidine deaminase (AID)-mediated diversification tools. As the oldest-emerging vertebrates sharing the same adaptive B and T cell receptor systems as humans, extant cartilaginous fishes allow a potential view of the ancestral immune system. In this review, we discuss breakthroughs we have made in studies of nurse shark (Ginglymostoma cirratum) T cell receptors demonstrating substantial integration of loci and diversification mechanisms in primordial B and T cell repertoires. We survey these findings in this shark model where they were first described, while noting corroborating examples in other vertebrate groups. We also consider other examples where the gnathostome common ancestry of the B and T cell receptor systems have allowed dovetailing of genomic elements and AID-based diversification approaches for the TCR. The cartilaginous fish seem to have retained this T/B cell plasticity to a greater extent than more derived vertebrate groups, but representatives in all vertebrate taxa except bony fish and placental mammals show such plasticity. [ABSTRACT FROM AUTHOR]

Placental mammals present 180 million-year-old Y chromosomes that have retained a handful of dosage-sensitive genes. However, the expression evolution of Y-linked genes across placental groups has remained largely unexplored. Here, we expanded the number of Y gametolog sequences by analyzing ten additional species from previously unexplored groups. We detected seven remarkably conserved genes across 25 placental species with known Y repertoires. We then used RNA-seq data from 17 placental mammals to unveil the expression evolution of XY gametologs. We found that Y gametologs followed, on average, a 3-fold expression loss and that X gametologs also experienced some expression reduction, particularly in primates. Y gametologs gained testis specificity through an accelerated expression decay in somatic tissues. Moreover, despite the substantial expression decay of Y genes, the combined expression of XY gametologs in males is higher than that of both X gametologs in females. Finally, our work describes several features of the Y chromosome in the last common mammalian ancestor. [ABSTRACT FROM AUTHOR]

It has long been challenging to uncover the molecular mechanisms behind striking morphological innovations such as mammalian pregnancy. We studied the power of a robust comparative orthology pipeline based on gene synteny to address such problems. We inferred orthology relations between human genes and genes from each of 43 other vertebrate genomes, resulting in ∼18,000 orthologous pairs for each genome comparison. By identifying genes that first appear coincident with origin of the placental mammals, we hypothesized that we would define a subset of the genome enriched for genes that played a role in placental evolution. We thus pinpointed orthologs that appeared before and after the divergence of eutherian mammals from marsupials. Reinforcing previous work, we found instead that much of the genetic toolkit of mammalian pregnancy evolved through the repurposing of preexisting genes to new roles. These genes acquired regulatory controls for their novel roles from a group of regulatory genes, many of which did in fact originate at the appearance of the eutherians. Thus, orthologs appearing at the origin of the eutherians are enriched in functions such as transcriptional regulation by Krüppel-associated box-zinc-finger proteins, innate immune responses, keratinization, and the melanoma-associated antigen protein class. Because the cellular mechanisms of invasive placentae are similar to those of metastatic cancers, we then used our orthology inferences to explore the association between placenta invasion and cancer metastasis. Again echoing previous work, we find that genes that are phylogenetically older are more likely to be implicated in cancer development. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT) is a neurohypophyseal hormone that influences a wide range of affiliative behaviors, such as pair-bonding and infant care, across mammals. The effects of OXT depend significantly on an adequate interaction with its receptor, OXTR. OXTR belongs to the G-protein coupled receptor family. The extracellular N-terminal domain of OXTR interacts with the linear C-terminal tail of OXT and is required for OXT binding. Across mammalian species there is a genetic diversity in OXTR terminal sequence. Previous work on primates has shown an association between OXTR phylogeny and monogamy. However, it is not clear whether this variation coevolved with either mating system (monogamy) or infant care behaviors (such as allomaternal care). Here, we take a phylogenetic comparative and evolutionary modeling approach across a wide range of placental mammals (n = 60) to test whether OXTR N-terminal variants co-evolved with either monogamy or allomaternal care behaviors. Our results indicate that the diversity in OXTR N-terminal region is unlikely to provide the underlying genetic bases for variation in mating system and/or allomaternal behavior as we find no evidence for co-evolution between protein sequence and affiliative behaviors. Hence, the role played by OXT in influencing affiliative behaviors is unlikely to be mediated by the genetic diversity of its receptor. • Oxytocin is known to mediate affiliative behavior. Its action is mediated via its receptor (OXTR). • Across mammals there is considerable variation in OXTR sequence. • It is not known whether this variation is correlated with monogamy and/or parental behavior. • We show that there is no evidence for correlated evolution between OXTR and allomaternal care. • We also show that there is minimal evidence for correlated evolution between OXTR and monogamy. [ABSTRACT FROM AUTHOR]

There are numerous phylogenetic reconstruction methods and models available—but which should you use and why? Important considerations in phylogenetic analyses include data quality, structure, signal, alignment length and sampling. If poorly modelled, variation in rates of change across proteins and across lineages can lead to incorrect phylogeny reconstruction which can then lead to downstream misinterpretation of the underlying data. The risk of choosing and applying an inappropriate model can be reduced with some critical yet straightforward steps outlined in this paper. We use the question of the position of the root of placental mammals as our working example to illustrate the topological impact of model misspecification. Using this case study we focus on using models in a Bayesian framework and we outline the steps involved in identifying and assessing better fitting models for specific datasets.

1-5% of human blood T cells are Vγ9Vδ2 T cells whose T cell receptor (TCR) contain a TRGV9/TRGJP rearrangement and a TRDV2 comprising Vδ2-chain. They respond to phosphoantigens (PAgs) like isopentenyl pyrophosphate or (E)-4-hydroxy-3-methylbut- 2-enyl-pyrophosphate (HMBPP) in a butyrophilin 3 (BTN3)-dependent manner and may contribute to the control of mycobacterial infections. These cells were thought to be restricted to primates, but we demonstrated by analysis of genomic databases that TRGV9, TRDV2, and BTN3 genes coevolved and emerged together with placental mammals. Furthermore, we identified alpaca (Vicugna pacos) as species with typical Vγ9Vδ2 TCR rearrangements and currently aim to directly identify Vγ9Vδ2 T cells and BTN3. Other candidates to study this coevolution are the bottlenose dolphin (Tursiops truncatus) and the nine-banded armadillo (Dasypus novemcinctus) with genomic sequences encoding open reading frames for TRGV9, TRDV2, and the extracellular part of BTN3. Dolphins have been shown to express Vγ9- and Vδ2-like TCR chains and possess a predicted BTN3-like gene homologous to human BTN3A3. The other candidate, the armadillo, is of medical interest since it serves as a natural reservoir for Mycobacterium leprae. In this study, we analyzed the armadillo genome and found evidence for multiple non-functional BTN3 genes including genomic context which closely resembles the organization of the human, alpaca, and dolphin BTN3A3 loci. However, no BTN3 transcript could be detected in armadillo cDNA. Additionally, attempts to identify a functional TRGV9/TRGJP rearrangement via PCR failed. In contrast, complete TRDV2 gene segments preferentially rearranged with a TRDJ4 homolog were cloned and co-expressed with a human Vγ9-chain in murine hybridoma cells. These cells could be stimulated by immobilized anti-mouse CD3 antibody but not with human RAJI-RT1Bl cells and HMBPP. So far, the lack of expression of TRGV9 rearrangements and BTN3 renders the armadillo an unlikely candidate species for PAg-reactive Vγ9Vδ2 T cells. This is in line with the postulated coevolution of the three genes, where occurrence of Vγ9Vδ2 TCRs coincides with a functional BTN3 molecule. [ABSTRACT FROM AUTHOR]

The timing of the placental mammal radiation has been the focus of debate over the efficacy of competing methods for establishing evolutionary timescales. Molecular clock analyses estimate that placental mammals originated before the Cretaceous-Paleogene (K-Pg) mass extinction, anywhere from the Late Cretaceous to the Jurassic. However, the absence of definitive fossils of placentals before the K-Pg boundary is compatible with a post-Cretaceous origin. Nevertheless, lineage divergence must occur before it can be manifest phenotypically in descendent lineages. This, combined with the non-uniformity of the rock and fossil records, requires the fossil record to be interpreted rather than read literally. To achieve this, we introduce an extended Bayesian Brownian bridge model that estimates the age of origination and, where applicable, extinction through a probabilistic interpretation of the fossil record. The model estimates the origination of placentals in the Late Cretaceous, with ordinal crown groups originating at or after the K-Pg boundary. The results reduce the plausible interval for placental mammal origination to the younger range of molecular clock estimates. Our findings support both the Long Fuse and Soft Explosive models of placental mammal diversification, indicating that the placentals originated shortly prior to the K-Pg mass extinction. The origination of many modern mammal lineages overlapped with and followed the K-Pg mass extinction. • The Bayesian Brownian bridge model estimates clade ages based on the fossil record • The model shows that placental mammals originated in the Cretaceous • Diversification of placental orders occurred after the K-Pg mass extinction • Clade age estimates can be obtained without molecular data or phylogenetic models Carlisle et al. use a Bayesian model to estimate the age of the origin of placental mammals based on the stratigraphic ranges and diversity of fossil and living taxa. The results point to a Late Cretaceous origin for placental mammals, in agreement with recent molecular timescales, with ordinal crown groups originating at or after the K-Pg boundary. [ABSTRACT FROM AUTHOR]

Gonads are very peculiar organs given their bipotential competence. Indeed, early differentiating genital ridges evolve into either of 2 very distinct organs: the testis or the ovary. Accumulating evidence now demonstrates that both genetic pathways must repress the other in order for the organs to differentiate properly, meaning that if this repression is disrupted or attenuated, the other pathway may completely or partially be expressed, leading to disorders of sex development. Among these disorders are the cases of XY male-tofemale and XX female-to-male sex reversals as well as true hermaphrodites, in which there is a discrepancy between the chromosomal and gonadal sex. Here, we review known cases of XY and XX sex reversals described in mammals, focusing mostly on domestic animals where sex reversal pathologies occur and on wild species in which deviations from the usual XX/XY system have been documented. [ABSTRACT FROM AUTHOR]

The Mass, Metabolism and Length Explanation (MMLE) was advanced in 1984 to explain the relationship between metabolic rate and body mass for birds and mammals. This paper reports on a modernized version of MMLE. MMLE deterministically computes the absolute value of Basal Metabolic Rate (BMR) and body mass for individual animals. MMLE is thus distinct from other examinations of these topics that use species-averaged data to estimate the parameters in a statistically best fit power law relationship such as BMR = a(bodymass)b. Beginning with the proposition that BMR is proportional to the number of mitochondria in an animal, two primary equations are derived that compute BMR and body mass as functions of an individual animal’s characteristic length and sturdiness factor. The characteristic length is a measureable skeletal length associated with an animal’s means of propulsion. The sturdiness factor expresses how sturdy or gracile an animal is. Eight other parameters occur in the equations that vary little among animals in the same phylogenetic group. The present paper modernizes MMLE by explicitly treating Froude and Strouhal dynamic similarity of mammals’ skeletal musculature, revising the treatment of BMR and using new data to estimate numerical values for the parameters that occur in the equations. A mass and length data set with 575 entries from the orders Rodentia, Chiroptera, Artiodactyla, Carnivora, Perissodactyla and Proboscidea is used. A BMR and mass data set with 436 entries from the orders Rodentia, Chiroptera, Artiodactyla and Carnivora is also used. With the estimated parameter values MMLE can calculate characteristic length and sturdiness factor values so that every BMR and mass datum from the BMR and mass data set can be computed exactly. Furthermore MMLE can calculate characteristic length and sturdiness factor values so that every body mass and length datum from the mass and length data set can be computed exactly. Whether or not MMLE can calculate a sturdiness factor value so that an individual animal’s BMR and body mass can be simultaneously computed given its characteristic length awaits analysis of a data set that simultaneously reports all three of these items for individual animals. However for many of the addressed MMLE homogeneous groups, MMLE can predict the exponent obtained by regression analysis of the BMR and mass data using the exponent obtained by regression analysis of the mass and length data. This argues that MMLE may be able to accurately simultaneously compute BMR and mass for an individual animal.

Background: Primary sex determination in placental mammals is a very well studied developmental process. Here, we aim to investigate the currently established scenario and to assess its adequacy to fully recover the observed phenotypes, in the wild type and perturbed situations. Computational modelling allows clarifying network dynamics, elucidating crucial temporal constrains as well as interplay between core regulatory modules. Results: Relying on a comprehensive revision of the literature, we define a logical model that integrates the current knowledge of the regulatory network controlling this developmental process. Our analysis indicates the necessity for some genes to operate at distinct functional thresholds and for specific developmental conditions to ensure the reproducibility of the sexual pathways followed by bi-potential gonads developing into either testes or ovaries. Our model thus allows studying the dynamics of wild type and mutant XX and XY gonads. Furthermore, the model analysis reveals that the gonad sexual fate results from the operation of two sub-networks associated respectively with an initiation and a maintenance phases. At the core of the process is the resolution of two connected feedback loops: the mutual inhibition of Sox9 and ß-catenin at the initiation phase, which in turn affects the mutual inhibition between Dmrt1 and Foxl2, at the maintenance phase. Three developmental signals related to the temporal activity of those sub-networks are required: a signal that determines Sry activation, marking the beginning of the initiation phase, and two further signals that define the transition from the initiation to the maintenance phases, by inhibiting the Wnt4 signalling pathway on the one hand, and by activating Foxl2 on the other hand. Conclusions: Our model reproduces a wide range of experimental data reported for the development of wild type and mutant gonads. It also provides a formal support to crucial aspects of the gonad sexual development and predicts gonadal phenotypes for mutations not tested yet. [ABSTRACT FROM AUTHOR]

We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5 million years ago. [ABSTRACT FROM AUTHOR]

Although great progress has been made in resolving the relationships of placental mammals, the position of several clades in Laurasiatheria remain controversial. In this study, we performed a phylogenetic analysis of 97 orthologs (46,152 bp) for 15 taxa, representing all laurasiatherian orders. Additionally, phylogenetic trees of laurasiatherian mammals with draft genome sequences were reconstructed based on 1608 exons (2,175,102 bp). Our reconstructions resolve the interordinal relationships within Laurasiatheria and corroborate the clades Scrotifera, Fereuungulata, and Cetartiodactyla. Furthermore, we tested alternative topologies within Laurasiatheria, and among alternatives for the phylogenetic position of Perissodactyla, a sister-group relationship with Cetartiodactyla receives the highest support. Thus, Pegasoferae (Perissodactyla + Carnivora + Pholidota + Chiroptera) does not appear to be a natural group. Divergence time estimates from these genes were compared with published estimates for splits within Laurasiatheria. Our estimates were similar to those of several studies and suggest that the divergences among these orders occurred within just a few million years. [ABSTRACT FROM PUBLISHER]

The flash electroretinogram (ERG) was used to characterize the scotopic retinal function in a marsupial. Key parameter values of the a- and b-waves of adult male sugar gliders, Petaurus breviceps breviceps, elicited with ganzfeld flashes were determined under dark- and light-adapted conditions. Using standard histological methods, the thicknesses of the major layers of the retina were assessed to provide insight into the nature of the ERG responses. The ERG and histological results were compared to corresponding data for placental C57Bl/6 mice to establish whether the functional retinal specialization that underlies scotopic visual function in a marsupial parallels that of a placental mouse. The sensitivity of the a- wave assessed with the Lamb and Pugh (Invest Ophthalmol Vis Sci 47:5138-5152, ) 'model' and that of the b-wave assessed with standard methods were lower in the sugar glider compared to the mouse. The thickness of the sugar glider retina was two-third of that of the mouse. The high-intensity flash ERG of the sugar glider substantially differed in shape from that of the mouse reflecting perhaps structural and functional differences between the two species at the level of the inner retina. [ABSTRACT FROM AUTHOR]

Noisy data, especially in combination with misalignment and model misspecification can have an adverse effect on phylogeny reconstruction; however, effective methods to identify such data are few. One particularly important class of noisy data is saturated positions. To avoid potential errors related to saturation in phylogenomic analyses, we present an automated procedure involving the step-wise removal of the most variable positions in a given data set coupled with a stopping criterion derived from correlation analyses of pairwise ML distances calculated from the deleted (saturated) and the remaining (conserved) subsets of the alignment. Through a comparison with existing methods, we demonstrate both the effectiveness of our proposed procedure for identifying noisy data and the effect of the removal of such data using a well-publicized case study involving placental mammals. At the least, our procedure will identify data sets requiring greater data exploration, and we recommend its use to investigate the effect on phylogenetic analyses of removing subsets of variable positions exhibiting weak or no correlation to the rest of the alignment. However, we would argue that this procedure, by identifying and removing noisy data, facilitates the construction of more accurate phylogenies by, for example, ameliorating potential long-branch attraction artefacts. [ABSTRACT FROM AUTHOR]

This paper presents a brief review of recent advances in the classification of mammals at higher levels using fossils and molecular clocks. It also discusses latest fossil discoveries from the Cretaceous — Eocene (66–55 m.y.) rocks of India and their relevance to our current understanding of placental mammal origins and diversifications. [ABSTRACT FROM AUTHOR]

Abstract: A rich source of material for comparative studies of the placenta is the collections made by pioneers in the field such as H.W. Mossman, A.A.W. Hubrecht and J.P. Hill. This overview gives a brief description of collections known to be available and information on how each can be accessed. Included are some of the major series of human and animal embryos, such as the Boyd and Carnegie collections, as these also house placental material. [Copyright &y& Elsevier]

The phylogenetic positions of the 4 clades, Euarchontoglires, Laurasiatheria, Afrotheria, and Xenarthra, have been major issues in the recent discussion of basal relationships among placental mammals. However, despite considerable efforts these relationships, crucial to the understanding of eutherian evolution and biogeography, have remained essentially unresolved. Euarchontoglires and Laurasiatheria are generally joined into a common clade (Boreoeutheria), whereas the position of Afrotheria and Xenarthra relative to Boreoeutheria has been equivocal in spite of the use of comprehensive amounts of nuclear encoded sequences or the application of genome-level characters such as retroposons. The probable reason for this uncertainty is that the divergences took place long time ago and within a narrow temporal window, leaving only short common branches. With the aim of further examining basal eutherian relationships, we have collected conserved protein-coding sequences from 11 placental mammals, a marsupial and a bird, whose nuclear genomes have been largely sequenced. The length of the alignment of homologous sequences representing each individual species is 2,168,859 nt. This number of sites, representing 2840 protein-coding genes, exceeds by a considerable margin that of any previous study. The phylogenetic analysis joined Xenarthra and Afrotheria on a common branch, Atlantogenata. This topology was found to fit the data significantly better than the alternative trees. [ABSTRACT FROM PUBLISHER]

Abstract: Sex determination in vertebrates is accomplished through a highly conserved genetic pathway. But surprisingly, the downstream events may be activated by a variety of triggers, including sex determining genes and environmental cues. Amongst species with genetic sex determination, the sex determining gene is anything but conserved, and the chromosomes that bear this master switch subscribe to special rules of evolution and function. In mammals, with a few notable exceptions, female are homogametic (XX) and males have a single X and a small, heterochromatic and gene poor Y that bears a male dominant sex determining gene SRY. The bird sex chromosome system is the converse in that females are the heterogametic sex (ZW) and males the homogametic sex (ZZ). There is no SRY in birds, and the dosage-sensitive Z-borne DMRT1 gene is a credible candidate sex determining gene. Different sex determining switches seem therefore to have evolved independently in different lineages, although the complex sex chromosomes of the platypus offer us tantalizing clues that the mammal XY system may have evolved directly from an ancient reptile ZW system. In this review we will discuss the organization and evolution of the sex chromosomes across a broad range of mammals, and speculate on how the Y chromosome, and SRY, evolved. [Copyright &y& Elsevier]

Abstract: The genomic database for a marsupial, the opossum Monodelphis domestica, is highly advanced. This allowed a complete analysis of the keratin I and keratin II gene cluster with some 30 genes in each cluster as well as a comparison with the human keratin clusters. Human and marsupial keratin gene clusters have an astonishingly similar organization. As placental mammals and marsupials are sister groups a corresponding organization is also expected for the archetype mammal. Since hair is a mammalian acquisition the following features of the cluster refer to its origin. In both clusters hair keratin genes arose at an interior position. While we do not know from which epithelial keratin genes the first hair keratins type-I and -II genes evolved, subsequent gene duplications gave rise to a subdomain of the clusters with many neighboring hair keratin genes. A second subdomain accounts in both clusters for 4 neighboring genes encoding the keratins of the inner root sheath (irs) keratins. Finally the hair keratin gene subdomain in the type-I gene cluster is interrupted after the second gene by a region encoding numerous genes for the high/ultrahigh sulfur hair keratin-associated proteins (KAPs). We also propose a tentative synteny relation of opossum and human genes based on maximal sequence conservation of the encoded keratins. The keratin gene clusters of the opossum seem to lack pseudogenes and display a slightly increased number of genes. Opossum keratin genes are usually longer than their human counterparts and also show longer intergenic distances. [Copyright &y& Elsevier]

Kelner and Dulbecco first reported in the 1940s and 1950s the reversal of ultraviolet damage in bacteria and phage by illumination with visible light. The first publications, reprinted here, represented the discovery of a widespread repair mechanism that was named “photoreactivation” (PHR), that directly reversed photoproducts to their individual pyrimidine components. Between them, these pioneers demonstrated that photoreactivation had a cellular basis, could be defined by wavelength optima indicating specific molecular photoreceptors, and had a widespread phyletic distribution except for its absence from placental mammals. [Copyright &y& Elsevier]

Any substantial change in brain size requires a change in the number of neurons and their supporting elements in the brain, which in turn requires an alteration in either the rate, or the duration of neurogenesis. The schedule of neurogenesis is surprisingly stable in mammalian brains, and increases in the duration of neurogenesis have predictable outcomes: late-generated structures become disproportionately large. The olfactory bulb and associated limbic structures may deviate in some species from this general brain enlargement: in the rhesus monkey, reduction of limbic system size appears to be produced by an advance in the onset of terminal neurogenesis in limbic system structures. Not only neurogenesis but also many other features of neural maturation such as process extension and retraction, follow the same schedule with the same predictability. Although the underlying order of event onset remains the same for all of the mammals we have yet studied, changes in overall rate of neural maturation distinguish related subclasses, such as marsupial and placental mammals, and changes in duration of neurodevelopment distinguish species within subclasses. A substantial part of the regularity of event sequence in neurogenesis can be related directly to the two dimensions of the neuraxis in a recently proposed prosomeric segmentation of the forebrain [Rubenstein et al., Science, 266: 578, 1994]. Both the spatial and temporal organization of development have been highly conserved in mammalian brain evolution, showing strong constraint on the types of brain adaptations possible. The neural mechanisms for integrative behaviors may become localized to those locations that have enough plasticity in neuron number to support them. [ABSTRACT FROM AUTHOR]

A recent paper by a science journalist in Nature shows major errors in understanding phylogenies, in this case of placental mammals. The underlying unrooted tree is probably correct, but the placement of the root just reflects a well-known error from the acceleration in the rate of evolution among some myomorph rodents. [ABSTRACT FROM PUBLISHER]

• Positive selection is identified in 14 sites of LAMP2 in placental mammals. • The positively selected sites appear in the N-domain and hinge domain of LAMP2. • A hotspot for positive selection is detected in the 135–144 codons interval. • Higher rate of evolution in LAMP2 in mega-bats is estimated compared to the rest of the phylogeny. Autophagy is the cellular process of removal of misfolded or damaged macromolecules and organelles. Experimental studies have demonstrated autophagy as a major mechanism of lifespan extension in long-lived mammals such as bats and mole rat rodents. Moreover, the role of this biological process has been well documented in protection against age-associated diseases and viral infection. However, studies on the molecular adaptive changes of autophagy factors during evolution are scarce. Here, we conducted a bioinformatics study of the molecular evolution of the Lysosomal Associated Membrane Protein 2 (LAMP2), as a rate-limiting factor in the lysosomal degradation stage of autophagy (the communal step of two of autophagy types: macroautophagy and chaperone-mediated). Analyzing LAMP2 across placental mammals, our phylogenetic-based maximum likelihood analyses indicate that the majority of the coding sites undergo purifying selection. However, around 27% of sites display a relaxation of purifying constraints (average ω = 0.42128), among which, 14 particular sites undergo positive selection (ω > 1). These sites are mostly located in the first luminal domain of LAMP2 (N-domain), with a hotspot region in the 135–144 codons interval. Therefore, the N-domain may account for the functional diversity and regulation of LAMP2. In addition, the identified positive selection sites could act as key regulatory sites in the LAMP2 function. On the other hand, testing the rate of evolution in LAMP2 along different clades of placental mammals revealed a relatively relaxed evolution in LAMP2 along megabats' clade. It is not clear yet whether an expedited evolution of LAMP2 in megabats has contributed to their reported up-regulation of autophagy. Finally, our data indicate positive selection sites along the ancestral branch of the clades of rodents, mouse-related rodents, and mole-rats; and suggest the potentially important regulatory role of these sites in LAMP2. Identifying the residues under positive selection, our findings pave the way for future experimental investigations to define how these selective substitutions have functionally affected autophagy. [ABSTRACT FROM AUTHOR]