Methylmalonyl Coenzyme A (CoA) Epimerase Deficiency, an Ultra-Rare Cause of Isolated Methylmalonic Aciduria With Predominant Neurological Features.

Methylmalonyl coenzyme A (CoA) epimerase (MCE) converts D-methylmalonyl-CoA into L-methylmalonyl CoA in the final common degradation pathway of valine, isoleucine, methionine, threonine, odd-chain fatty acids, and cholesterol side chains. Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where methylmalonic acid, methylcitrate, 3-hydroxypropionate, and propionylcarnitine are accumulated. We describe two novel pediatric patients and review the previously reported cases of MCE deficiency. Including our two novel patients, at least 24 cases of MCE deficiency have been described, with a broad clinical spectrum ranging from asymptomatic to severely neurologically impaired patients. Our patients are siblings of Arabic origin who presented with metabolic decompensation with coma and epilepsy during infancy. Methylmalonic aciduria was disclosed, L-methylmalonyl-CoA mutase deficiency was assumed, and they were treated accordingly. When first seen in our country, aged 10 and four years, respectively, both presented severe intellectual disability and spasticity. The younger had an ataxic gait, and the older was wheelchair-ridden. The study of the MMUT, MMAA, MMAB, and MMADHC genes was normal. Subsequently, the pathogenic variant c.139C>T (p.Arg47*) in the MCEE gene was identified in homozygosity in both patients, leading to the diagnosis of MCE deficiency (Online Mendelian Inheritance in Man (OMIM®) 251120, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, MD, USA). Most patients were homozygous for that variant (83% of the alleles). Correct diagnosis allowed treatment adequacy and genetic counseling. Methylmalonyl-CoA epimerase deficiency shares a similar biochemical profile with other rare genetic disorders. Patients present with overlapping clinical features with predominant neurological manifestations; genetic testing is indispensable for diagnosis. We found no association between genotype and biochemical and clinical phenotypes.

Not just in the past: Racist and sexist biases still permeate biology, anthropology, medicine, and education.

In the past decades, it has been increasingly recognized that some areas of science, such as anthropology, have been plagued by racist, Western-centric, and/or sexist biases. Unfortunately, an acculturation process to racism and sexism has been occurring for generations leading to systemic inequities that will take a long time to disappear. Here, we highlight the existence of current examples of racism, Western-centrism and sexism within: (1) the most popular anatomical atlases used in biological, anthropological and medical education; (2) prominent natural history museums and World Heritage Sites; (3) biological and anthropological scientific research publications; and (4) popular culture and influential children's books and educational materials concerning human biology and evolution.

Comparative cranio-mandibular myology of three species of Batoidea from the Southern Gulf of California, Mexico.

The mandibular apparatus of batoids (skates, electric rays, guitarfishes, stingrays, and sawfishes) is composed of a few skeletal elements to which the muscular bundles, responsible for all movements involved in the feeding mechanism, are inserted. The description of the different mandibular morphologies can help to understand the different feeding guilds in this group. In this study, we examined the cranio-mandibular myology of adult Rostroraja velezi, Narcine entemedor, and Zapteryx exasperata, three species of rays that coexist in the Southern Gulf of California, Mexico. This study described the muscles on the ventral and the dorsal surfaces for each species, identified the origins and insertions of these muscles, as well as the general characteristics of muscle morphology. There were 17 and 18 muscle bundles attached to the feeding apparatus, including five on the dorsal surface. Only the levator rostri, which elevates the rostrum during feeding, showed considerable differences in shape and size among species. The muscles of the adductor complex showed the greatest differences in size among the three species. N. entemedor presented the exclusive muscle X in the lower mandibular area and the extreme reduction of the coracohyoideus in the pharyngeal area derived from the absence of the basihyal cartilage. The information generated in our study supports the morphological specialization of electric rays (N. entemedor) for an almost exclusive suction feeding strategy.

Prospective study of loss of health-related quality adjusted life years in children and their families due to uncomplicated and hospitalised varicella.

INTRODUCTION AND AIMS: Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. METHODS: Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. RESULTS: Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9-2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3-6.1) and 1.3 days/primary carer (95 % CI 1.2-1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4-10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8-29.0) and 8.5 days/primary carer (95 % CI 7.4-9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. CONCLUSIONS: The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.

Mucopolysaccharidosis Type I: The Importance of Early Diagnosis for Adequate Treatment.

Mucopolysaccharidoses are rare lysosomal storage disorders in which glycosaminoglycans accumulate in tissues, causing multiorgan dysfunction. Mucopolysaccharidosis type I is an autosomal recessive disease caused by a deficiency of the enzyme alpha-L-iduronidase, resulting in the accumulation of dermatan and heparan sulfate. Early diagnosis is crucial for early treatment and improved outcomes. We report the case of a female child with classic clinical features who was diagnosed early which allowed hematopoietic stem cell transplantation and slowed disease progression. She presented at birth with linea alba and umbilical and inguinal hernias. Since the first months of life, she had recurrent respiratory infections. At nine months, a motor delay was noticed, and at 20 months, craniosynostosis was corrected with surgery. Coarse facial features, thoracolumbar kyphosis, and hepatomegaly prompted a urinary glycosaminoglycan study at 22 months, which showed elevated levels. Alfa-L-iduronidase activity in dried blood spot testing was low, compatible with mucopolysaccharidosis type I. Molecular testing of gene IDUA, performed for genetic counseling, revealed the pathogenic variants c.1205G>A (p.Trp402Ter) and c.1598C>G (p.Pro533Arg) in compound heterozygosity. At 26 months, her development quotient was average for her age. She started enzyme replacement therapy at 29 months and underwent hematopoietic stem cell transplantation at 33 months, which softened the coarse features, reduced respiratory infections, and improved hepatomegaly. However, at age five, her development quotient was 76 (mean = 100, standard deviation = 15). This intellectual impairment might have been prevented with an earlier diagnosis and treatment.

The arteries of the musculoskeletal system of siamangs, and a comparison with other hylobatids, greater apes, and humans.

Limited research on the gross anatomy of the blood vessels has been conducted on hylobatids, or lesser apes, so far. Here, we present a detailed study of the arteries of siamangs (Symphalangus) and compare our findings with data compiled from our previous studies as well as from the literature about other hylobatids, greater apes, and humans. In particular, a three-dimensional full-body computed tomography data set of a siamang neonate was analyzed in detail for this study, with notable findings in the head and neck, thorax, upper limb, abdomen and pelvis, and lower limb. Of the 62 arteries that we studied in detail, a total of 20 arteries that have never been described in detail in hylobatids are reported in this study. Key similarities to other apes differing from humans include the existence of a humeral common circumflex trunk and the origination of the dorsalis pedis from the posterior tibial artery or saphenous artery instead of the anterior tibial artery. Similarities to humans differing from other apes include the separation of the lingual and facial arteries and the origination of the profunda brachii from the brachial artery instead of the axillary artery. Our research and broader comparisons, therefore, contribute to knowledge about the soft tissues of hylobatids, other apes, and primates in general and facilitate a better understanding of the anatomical evolution and key differences and similarities among these taxa.

Comparative development of limb musculature in phylogenetically and ecologically divergent lizards.

BACKGROUND: Squamate reptiles (lizards, snakes, and amphisbaenians) exhibit incredible diversity in their locomotion, behavior, morphology, and ecological breadth. Although they often are used as models of locomotor diversity, surprisingly little attention has been given to muscle development in squamate reptiles. In fact, the most detailed examination was conducted almost 80 years ago and solely focused on the proximal limb regions. Herein, we present forelimb and hindlimb muscle morphogenesis data for three lizard species with different locomotion and feeding strategies: the desert grassland whiptail lizard, the central bearded dragon, and the veiled chameleon. This study fills critical gaps in our understanding of muscle morphogenesis in squamate reptiles and presents a comparative and temporospatial analysis of muscle development. RESULTS: Our results reveal a conserved pattern of early muscle development among lizards with different adult morphologies and ecologies. The variations that exist are concentrated in distal regions, particularly the specialized autopodia of chameleons, where differentiation of muscles associated with the digits is delayed. CONCLUSIONS: The chameleon autopod provides an example of major evolutionary modifications to the skeleton with only minor disruption of the conserved order and pattern of limb muscle development. This robustness of muscle patterning facilitates the evolution of extreme yet functional phenotypes.

Hiding in Plain Sight-ancient Chinese anatomy.

For thousands of years, scientists have studied human anatomy by dissecting bodies. Our knowledge of their findings is limited, however, both by the subsequent loss of many of the oldest texts, and by a tendency toward a Eurocentric perspective in medicine. As a discipline, anatomy tends to be much more familiar with ancient Greek texts than with those from India, China, or Persia. Here, we show that the Mawangdui medical texts, entombed in the Mawangdui burial site in Changsha, China 168 BCE, are the oldest surviving anatomical atlas in the world. These medical texts both predate and inform the later acupuncture texts which have been the foundation for acupuncture practice in the subsequent two millennia. The skills necessary to interpret them are diverse, requiring the researcher firstly to read the original Chinese, and secondly to perform the anatomical investigations that allow a re-viewing of the structures that the texts refer to. Acupuncture meridians are considered to be esoteric in nature, but these texts are clearly descriptions of the physical body. As such, they represent a previously hidden chapter in the history of anatomy, and a new perspective on acupuncture.

Morphological variability of the plantaris muscle origin in human fetuses.

INTRODUCTION: The plantaris muscle (PM) is a small, fusiform muscle located between the gastrocnemius muscle (GM) and soleus muscle (SM). PM supports movements of the knee and ankle. This muscle presents a great variability, and also has a high clinical significance. Nevertheless, data concerns morphology and morphometry of the origin of PM in human fetuses are scarce. MATERIAL AND METHODS: Forty-seven spontaneously-aborted human fetuses (23 male, 24 female) aged 18-38 weeks of gestation were examined. The morphology and morphometry of the origin of PM were evaluated. RESULTS: PM was present in 74 lower limbs (78.7%), and absent on 20 limbs (21.3%). We distinguished VI types of the proximal attachment of PM. Belly width and thickness, as well as thickness of the tendon and MT junction differed significantly between types of PM origin. CONCLUSIONS: We distinguished six (I-VI) types of origin of PM in human fetuses. The most common type was type Ia, characterized by an attachment to the lateral head of GM, lateral femoral condyle and to the knee joint capsule. Our results of PM anatomical variation in fetuses will pave the way for detailed comparisons with studies carried out on adult cadavers.

Morphological variability of the fibularis longus tendon in human fetuses.

INTRODUCTION: The morphological variability of the fibularis longus tendon (FLT) in adults is well understood. However, no comprehensive classification exists in human fetuses. The goal of this study was to prepare the first comprehensive classification of the fibularis longus tendon based on its insertion in human fetuses. MATERIAL AND METHODS: Forty-seven spontaneously-aborted human fetuses were examined: 38 male, 56 female, a total of 94 lower limbs (Central European population). Age ranged from18-38 weeks of gestation at death. RESULTS: The classification comprised three types of FLT. The most common type was Type I (49%), characterized by the single distal attachment. This type was divided into two subtypes (A-B): A - the tendon inserts to the lateral tubercle of the base of the 1st metatarsal bone, B - the tendon inserts to the head of the 1st metatarsal bone. The second most type was Type II, characterized by a bifurcated distal attachment (24.5%). This type was divided into three subtypes (A-C): A - the main tendon inserts to the lateral tubercle of the base of the 1st metatarsal bone and the accessory band inserts to the medial cuneiform bone; B - the strong, main tendon inserts to both the base of the 1st metatarsal bone and medial cuneiform bone, including the first metatarsal-cuneiform joint, and the accessory bands inserts to the fourth interosseus dorsalis muscle; C - the main tendon inserts to the lateral tubercle of the base of the 1st metatarsal bone and the accessory band inserts to the first interosseus dorsalis muscle. The rarest type was Type III, characterized by a trifurcated distal attachment: the main tendon inserts to the lateral tubercle of the base of the 1st metatarsal bone and the first accessory band inserts to the medial cuneiform bone and the second accessory bands inserts to the first interosseus dorsalis muscle. The anterior frenular ligament was observed in 16% of all cases, and posterior frenular ligament in 6.4%. CONCLUSION: The FLT displays high morphological variability. The proposed classification consists of three main types, with Type I and Type II divided into sub-types; it also provides additional data regarding its accessory tendon bands.

The Visible Ape Project: A free, comprehensive, web-based anatomical atlas for scientists and veterinarians designed to raise public awareness about apes.

The Visible Ape Project (VAP) is a free online platform providing unprecedented access to a suite of resources designed to comprehensively illustrate and educate about the anatomy of our closest relatives, the apes. It contains photographs, magnetic resonance images, and computed tomography scans, as well as three-dimensional models that can be manipulated to explore homologies and variations in soft and hard tissues in hylobatids, orangutans, gorillas, chimpanzees, and bonobos. Based at Howard University, a historically black university, it aims to reach communities underrepresented in anthropology and evolutionary biology, providing educational materials appropriate for K-12 and college classrooms in both English and Spanish. Accordingly, VAP incorporates outreach activities to disseminate science and promote awareness of apes, forming partnerships with veterinarians and conservationists in Africa and Asia. In this paper, we present an introduction to the website to illustrate how this accessible, evolving resource can support evolutionary anthropology and related disciplines.

Anatomical comparison across heads, fore- and hindlimbs in mammals using network models.

Animal body parts evolve with variable degrees of integration that nonetheless yield functional adult phenotypes: but, how? The analysis of modularity with Anatomical Network Analysis (AnNA) is used to quantitatively determine phenotypic modules based on the physical connection among anatomical elements, an approach that is valuable to understand developmental and evolutionary constraints. We created anatomical network models of the head, forelimb, and hindlimb of two taxa considered to represent a 'generalized' eutherian (placental: mouse) and metatherian (marsupial: opossum) anatomical configuration and compared them with our species, which has a derived eutherian configuration. In these models, nodes represent anatomical units and links represent their physical connection. Here, we aimed to identify: (1) the commonalities and differences in modularity between species, (2) whether modules present a potential phylogenetic character, and (3) whether modules preferentially reflect either developmental or functional aspects of anatomy, or a mix of both. We predicted differences between networks of metatherian and eutherian mammals that would best be explained by functional constraints, versus by constraints of development and/or phylogeny. The topology of contacts between bones, muscles, and bones + muscles showed that, among all three species, skeletal networks were more similar than musculoskeletal networks. There was no clear indication that humans and mice are more alike when compared to the opossum overall, even though their musculoskeletal and skeletal networks of fore- and hindlimbs are slightly more similar. Differences were greatest among musculoskeletal networks of heads and next of forelimbs, which showed more variation than hindlimbs, supporting previous anatomical studies indicating that in general the configuration of the hindlimbs changes less across evolutionary history. Most observations regarding the anatomical networks seem to be best explained by function, but an exception is the adult opossum ear ossicles. These ear bones might form an independent module because the incus and malleus are involved in forming a functional primary jaw that enables the neonate to attach to the teat, where this newborn will complete its development. Additionally, the human data show a specialized digit 1 module (thumb/big toe) in both limb types, likely the result of functional and evolutionary pressures, as our ape ancestors had highly movable big toes and thumbs.

Not deconstructing serial homology, but instead, the a priori assumption that it generally involves ancestral anatomical similarity: An answer to Kuznetsov's paper.

I am very thankful to Kuznetsov for his comments on our recent paper about serial structures published in this journal. I hope this is just the beginning of a much wider, and holistic, discussion on the evolution of serial homologous structures, and of so-called "serial structures" in general, whether they are truly serial homologs or the secondary result of homoplasy. Strangely, Kuznetsov seems to have missed the main point of our paper, what is particularly puzzling as this point is clearly made in the very title of our paper. For instance, he states that "Siomava et al. claim that the serial homologues are false because they are ancestrally anisomeric (dissimilar)' and that" Siomava et al., (Siomava et al., Journal of Morphology, 2020, 281, 1110-1132) expected that if serial homology was true, then the serial homologs would be identical at the start and then only diverge. " However, our paper clearly did not state this. Instead, we stated that (a) serial homology is a real phenomenon, and (b) ancestral dissimilarity is actually likely the norm, and not the exception, within serial homology. In particular, our paper showed that, as clearly stated in its title and abstract, within the evolution of serial homologues these structures "many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism." Serial homology is therefore a genuine and much widespread phenomenon within the evolution of life in this planet. It is clearly one of the most important issues-and paradoxically one of the less understood, precisely because of the a priori acceptance of long-standing assumptions that have never been empirically tested, some of them repeated in Kuznetsov's paper-within macroevolution and comparative anatomy.

Deconstructing the long-standing a priori assumption that serial homology generally involves ancestral similarity followed by anatomical divergence.

It has long been assumed that serial homologues are ancestrally similar-polysomerism resulting from a "duplication" or "repetition" of forms-and then often diverge-anisomerism, for example, as they become adapted to perform different tasks as is the case with the forelimb and hind limbs of humans. However, such an assumption, with crucial implications for comparative, evolutionary, and developmental biology, and for evolutionary developmental biology, has in general not really been tested by a broad analysis of the available empirical data. Perhaps not surprisingly, more recent anatomical comparisons, as well as molecular knowledge of how, for example, serial appendicular structures are patterned along with different anteroposterior regions of the body axis of bilateral animals, and how "homologous" patterning domains do not necessarily mark "homologous" morphological domains, are putting in question this paradigm. In fact, apart from showing that many so-called "serial homologues" might not be similar at all, recent works have shown that in at least some cases some "serial" structures are indeed more similar to each other in derived taxa than in phylogenetically more ancestral ones, as pointed out by authors such as Owen. In this article, we are taking a step back to question whether such assumptions are actually correct at all, in the first place. In particular, we review other cases of so-called "serial homologues" such as insect wings, arthropod walking appendages, Dipteran thoracic bristles, and the vertebrae, ribs, teeth, myomeres, feathers, and hairs of chordate animals. We show that: (a) there are almost never cases of true ancestral similarity; (b) in evolution, such structures-for example, vertebra-and/or their subparts-for example, "transverse processes"-many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism.

Cranial or postcranial-Dual origin of the pectoral appendage of vertebrates combining the fin-fold and gill-arch theories?

Two main theories have been used to explain the origin of pectoral and pelvic appendages. The "fin-fold theory" proposes that they evolved from a trunk bilateral fin fold, while Gegenbaur's theory assumes they derived from the head branchial arches. However, none of these theories has been fully supported. The "fin-fold" theory is mainly often accepted due to some existing developmental data, but recent developmental studies have revived Gegenbaur's theory by revealing common mechanisms underlying the patterning of branchial arches and paired appendages. Here I review developmental data and many others lines of evidence, which lead to a crucial question: might the apparent contradictions between the two theories be explained by a dual origin of the pectoral appendage, that is, the pectoral girdle and fin/limb being mainly related to the head and trunk, respectively? If this is so then (a) the pectoral and pelvic girdles would not be serial homologues; (b) the term "developmental serial homologues" could only potentially be applied to the pectoral and pelvic fins/limbs. Fascinatingly, in a way this would be similar to what Owen had already suggested, more than 170 years ago: that the pectoral and pelvic girdles are mainly related to the head and trunk, respectively.

Comparative anatomy of the fin muscles of non-sarcopterygian fishes, with notes on homology and evolution.

Limited gross anatomical information about the muscles of fins, in particular those of the median fins, creates substantial gaps in the comparative anatomy, homologies, and evolution of these muscles across fishes. The scarcity of data also makes it difficult to interpret results obtained in developmental studies done in model organisms, such as zebrafish. To overcome these gaps, we provide descriptions of the configuration of all appendicular muscles of Amia, median fins of Polypterus, and the dorsal and anal fins of Lepisosteus and Chondrostei. The musculature of other species, including sharks and sturgeons, is also revised. We describe muscles that were previously overlooked, report sexual dimorphism in the muscles of the anal fin of Polypterus, and reveal muscle variations within Polypterus males. Species dissected for the present study thus represent all major non-sarcopterygian extant clades of gnathostomes, i.e. Chondrichthyes, Polypteriformes, Chondrostei, Lepisosteiformes, Amiiformes and Teleostei. Moreover, we compare our observations with the relatively few works that have provided information about muscles of at least some fins of these taxa in order to provide a broad discussion on - and detailed schemes showing - the major evolutionary patterns within the appendicular musculature of these fishes. Such discussion provides an opportunity for a more comprehensive understanding of appendicular evolution and fish evolution in particular and of gnathostome and morphological evolution in general.

Evolution of Hindlimb Muscle Anatomy Across the Tetrapod Water-to-Land Transition, Including Comparisons With Forelimb Anatomy.

Tetrapod limbs are a key innovation implicated in the evolutionary success of the clade. Although musculoskeletal evolution of the pectoral appendage across the fins-to-limbs transition is fairly well documented, that of the pelvic appendage is much less so. The skeletal elements of the pelvic appendage in some tetrapodomorph fish and the earliest tetrapods are relatively smaller and/or qualitatively less similar to those of crown tetrapods than those of the pectoral appendage. However, comparative and developmental works have suggested that the musculature of the tetrapod forelimb and hindlimb was initially very similar, constituting a "similarity bottleneck" at the fins-to-limbs transition. Here, we used extant phylogenetic bracketing and phylogenetic character optimization to reconstruct pelvic appendicular muscle anatomy in several key taxa spanning the fins-to-limbs and water-to-land transitions. Our results support the hypothesis that transformation of the pelvic appendages from fin-like to limb-like lagged behind that of the pectoral appendages. Compared to similar reconstructions of the pectoral appendages, the pelvic appendages of the earliest tetrapods had fewer muscles, particularly in the distal limb (shank). In addition, our results suggest that the first tetrapods had a greater number of muscle-muscle topological correspondences between the pectoral and pelvic appendages than tetrapodomorph fish had. However, ancestral crown-group tetrapods appear to have had an even greater number of similar muscles (both in terms of number and as a percentage of the total number of muscles), indicating that the main topological similarity bottleneck between the paired appendages may have occurred at the origin of the tetrapod crown group. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 303:218-234, 2020. © 2018 American Association for Anatomy.

Human enhancement: Genetic engineering and evolution.

Genetic engineering opens new possibilities for biomedical enhancement requiring ethical, societal and practical considerations to evaluate its implications for human biology, human evolution and our natural environment. In this Commentary, we consider human enhancement, and in particular, we explore genetic enhancement in an evolutionary context. In summarizing key open questions, we highlight the importance of acknowledging multiple effects (pleiotropy) and complex epigenetic interactions among genotype, phenotype and ecology, and the need to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). We also propose that a practicable distinction between 'therapy' and 'enhancement' may need to be drawn and effectively implemented in future regulations. Overall, we suggest that it is essential for ethical, philosophical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines. Lay Summary: This Commentary explores genetic enhancement in an evolutionary context. We highlight the multiple effects associated with germline heritable genetic intervention, the need to consider the unit of impact to human populations and their natural environment, and propose that a practicable distinction between 'therapy' and 'enhancement' is needed.

Development of human limb muscles based on whole-mount immunostaining and the links between ontogeny and evolution.

We provide the first detailed ontogenetic analysis of human limb muscles using whole-mount immunostaining. We compare our observations with the few earlier studies that have focused on the development of these muscles, and with data available on limb evolution, variations and pathologies. Our study confirms the transient presence of several atavistic muscles - present in our ancestors but normally absent from the adult human - during normal embryonic human development, and reveals the existence of others not previously described in human embryos. These atavistic muscles are found both as rare variations in the adult population and as anomalies in human congenital malformations, reinforcing the idea that such variations/anomalies can be related to delayed or arrested development. We further show that there is a striking difference in the developmental order of muscle appearance in the upper versus lower limbs, reinforcing the idea that the similarity between various distal upper versus lower limb muscles of tetrapod adults may be derived.

Evolution of facial muscle anatomy in dogs.

Domestication shaped wolves into dogs and transformed both their behavior and their anatomy. Here we show that, in only 33,000 y, domestication transformed the facial muscle anatomy of dogs specifically for facial communication with humans. Based on dissections of dog and wolf heads, we show that the levator anguli oculi medialis, a muscle responsible for raising the inner eyebrow intensely, is uniformly present in dogs but not in wolves. Behavioral data, collected from dogs and wolves, show that dogs produce the eyebrow movement significantly more often and with higher intensity than wolves do, with highest-intensity movements produced exclusively by dogs. Interestingly, this movement increases paedomorphism and resembles an expression that humans produce when sad, so its production in dogs may trigger a nurturing response in humans. We hypothesize that dogs with expressive eyebrows had a selection advantage and that "puppy dog eyes" are the result of selection based on humans' preferences.