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Diving and dietary adaptations in sperm whales. The loss of AMPD3 (red, Supplementary Fig. 19) is likely an adaptation to the extreme diving ability of sperm whales. AMPD3 deaminates adenosine monophosphate (AMP) to inosine monophosphate (IMP) in erythrocytes. AMPD3 loss increases the level of ATP (an allosteric hemoglobin effector), which facilitates O 2 release, as illustrated by the O 2-hemoglobin dissociation curve (wildtype, black; AMPD3 knockout, red 28 ). In contrast, the loss of the vitamin A synthesizing enzyme BCO1 (blue, Supplementary Fig. 20) in sperm whales is likely a consequence of relaxed selection after sperm whales adapted to their specialized diet that mainly consists of vitamin A-rich but beta-carotene poor squid. The absence of its substrate (beta-carotene) likely made this enzyme obsolete, leading to the loss of BCO1
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Identifying the genomic changes that underlie phenotypic adaptations is a key challenge in evolutionary biology and genomics. Loss of protein-coding genes is one type of genomic change with the potential to affect phenotypic evolution. Here, we develop a genomics approach to accurately detect gene losses and investigate their importance for adaptiv...
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... contrast, if the gene loss event is a consequence of relaxed selection following an adaptation, we expect that knock- out phenotypes and molecular function do not have a causal relationship to the adaptive phenotype or that the gene was lost after the evolution of this phenotype. By making use of existing gene knockouts in mouse or loss-of-function mutations in human individuals and by dating gene loss events, we discovered a number of previously unknown gene losses ( Supplementary Fig. 13 and Supplementary Table 4), some of which may have contributed to morphological, physiological, and metabolic adaptations in mammals, while others are likely a consequence of adaptive evolution. ...
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... erythrocyte ATP level by threefold 28 . Since ATP is an allosteric effector that stabilizes O 2 -unloaded hemoglobin in vertebrates, the loss of AMPD3 results in a reduced O 2 affinity of hemoglobin 28 . This is probably adaptive for long-diving sperm whales as a lower affinity facilitates O 2 release from hemoglobin to the O 2 -depleted tissue ( Fig. 3 and Supplementary Note 2). Remarkably, crocodiles that can stay submerged for over an hour also show a reduced O 2 affinity of hemoglobin; however, this reduction is mediated by bicarbonate ions (HCO 3 − ) instead of ATP 29 . Thus, the loss of AMPD3 could be a novel adaptive mechanism to improve O 2 transport from blood to tissue in a ...
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... a consequence of a dietary specialization. Sperm whales feed predominantly on squid that contain no or very little beta- carotene, but are rich in vitamin A. This likely explains why the sperm whale is the only mammal in our data set that has lost the BCO1 gene, which encodes an enzyme that cleaves beta-carotene into retinal (a form of vitamin A) (Fig. 3 Supplementary Fig. 19) is likely an adaptation to the extreme diving ability of sperm whales. AMPD3 deaminates adenosine monophosphate (AMP) to inosine monophosphate (IMP) in erythrocytes. AMPD3 loss increases the level of ATP (an allosteric hemoglobin effector), which facilitates O 2 release, as illustrated by the O 2 -hemoglobin ...
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... a proof of concept, we searched for genes that are lost in four mammals that independently lost tooth enamel (Fig. 5a) and identified previously known losses of the tooth-specific genes MMP20 and C4orf26 15 that are essential for enamel formation (Fig. 5b, Supplementary Note 6, and Supplementary Table 6). As a novel result, we detected the convergent loss of ACP4 ( Fig. 5b and Supplementary Fig. 33), a gene that is associated with the enamel disorder amelogenesis imperfecta 46 . This shows that a genome-wide search can identify known and novel gene losses that are involved in the independent loss of enamel. ...
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... the scales of these two species have different developmental origins (made of keratin in pangolins and bone in armadillos), it is unlikely to find gene losses that play a causal role in scale formation; instead, forward genomics may identify genes that are lost as a consequence of scale evolution, which could reveal unknown aspects related to body armor. Surprisingly, we found that both scaly mammals are the only species in our data set that have lost the DDB2 gene (Fig. 5, Supplementary Note 7, Supplementary Fig. 34, and Supplemen- tary Table 7). DDB2 detects pyrimidine dimers caused by UV light and triggers nucleotide excision DNA repair 47 . ...
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... loss of the same gene could contribute to similar phenotypic adaptations shared between two lineages. Searching for gene losses shared between the fully aquatic cetacean and manatee lineages revealed KLK8, a gene loss that correlates with skin and neuroanatomical differences of aquatic mammals 50 . In addition, we discovered the loss of MMP12 (Fig. 5, Supplementary Note 8, Supplementary Fig. 35, and Supplementary Table 8), which provides the first insights into the molecular mechanism underlying a unique breathing adaptation. The so-called "explosive exhalation" allows cetaceans and manatees to renew ~90% of the air in a single breath 51 , and is advantageous for fully aquatic mammals by clearing the blow- hole/nostrils ...
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... In 4 contrast to TGM4, which is also absent in the closest land-dwelling relatives of cetaceans (Fig. 4A), 5 TGM3, TGM5, TGM6 and TGM7 have been lost specifically in cetaceans. The loss of TGM5 was 6 reported previously (Sharma et al. 2018). Detailed sequence analysis of TGM6 showed that, besides 7 other mutations, a frameshift mutation in exon 5 is shared among all cetaceans investigated (Fig. 4B), 8 ...
Transglutaminases (TGMs) cross-link proteins by introducing covalent bonds between glutamine and lysine residues. These cross-links are essential for epithelial cornification which enables tetrapods to live on land. Here, we investigated which evolutionary adaptations of vertebrates were associated with specific changes in the family of TGM genes. We determined the catalog of TGMs in the main clades of vertebrates, performed a comprehensive phylogenetic analysis of TGMs, and localized the distribution of selected TGMs in tissues. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM, with orthologs being expressed in the cornified teeth of the lamprey, a basal vertebrate. Gene duplications led to the origin of TGM10 in stem vertebrates, the origin of TGM2 in jawed vertebrates, and an increasing number of epithelium-associated TGM genes in the lineage leading to terrestrial vertebrates. TGM9 is expressed in the epithelial egg tooth, and its evolutionary origin in stem amniotes coincided with the evolution of embryonic development in eggs that are surrounded by a protective shell. Conversely, viviparous mammals have lost both the epithelial egg tooth and TGM9. TGM3 and TGM6 evolved as regulators of cornification in hair follicles and underwent pseudogenization upon the evolutionary loss of hair in cetaceans. Taken together, this study reveals the gain and loss of vertebrate TGM genes in association with the evolution of cornified skin appendages and suggests an important role of TGM9 in the evolution of amniotes.
... By linking the physiological tolerance of organisms to evolutionary and biogeographic processes, researchers have found that AANAT duplication and loss occurred in the middle Eocene when a more seasonal climate emerged [24,59]. Based on the potential causal relationship between genetic and phenotypic adaptation [60], we hypothesized that the adaptive evolution of AANAT may be linked to its adjustment of hibernation rhythms. ...
Arylalkylamine N-acetyltransferase (AANAT) is a crucial rate-limiting enzyme in the synthesis of melatonin. AANAT has been confirmed to be independently duplicated and inactivated in different animal taxa in order to adapt to the environment. However, the evolutionary forces associated with having a single copy of AANAT remain unclear. The greater horseshoe bat has a single copy of AANAT but exhibits different hibernation rhythms in various populations. We analyzed the adaptive evolution at the gene and protein levels of AANAT from three distinct genetic lineages in China: northeast (NE), central east (CE), and southwest (SW). The results revealed greater genetic diversity in the AANAT loci of the NE and CE lineage populations that have longer hibernation times, and there were two positive selection loci. The catalytic capacity of AANAT in the Liaoning population that underwent positive selection was significantly higher than that of the Yunnan population (p < 0.05). This difference may be related to the lower proportion of α helix and the variation in two interface residues. The adaptive evolution of AANAT was significantly correlated with climate and environment (p < 0.05). After controlling for geographical factors (latitude and altitude), the evolution of AANAT by the negative temperature factor was represented by the monthly mean temperature (r = −0.6, p < 0.05). The results identified the gene level variation, functional adaptation, and evolutionary driving factors of AANAT, provide an important foundation for further understanding the adaptive evolution of the single copy of AANAT in pteropods, and may offer evidence for adaptive hibernation rhythms in bats.
... doi: bioRxiv preprint (Rutherford and Lindquist, 1998) and Arabidopsis (Queitsch et al., 2002). Similarly, the loss of AMPD3 in sperm whales may have allowed for the evolution of long-diving times, while the loss of SLC22A12 (URAT1), SLC2A9 (GLUT9), and SLC22A6 (OAT1) may have facilitated the evolution of fruit-based diet in bats (Sharma et al., 2018). Thus, gene loss can reveal previous hidden morphological variation and break ancestral developmental constraints, leading to the evolution of novel phenotypes (Montrose et al., 2024b). ...
... The copyright holder for this preprint (which this version posted https://doi.org/10.1101https://doi.org/10. /2024 of Dollo parsimony is to minimize the number of 1→0 reversions, which is the ideal model for reconstructing the evolution of gene loss events across a phylogeny because, once lost, a homologous gene can never reevolve (Sharma et al., 2018). Branch support was assessed with 100 bootstrap replicates and a parsimony variant of the Shimodaira-Hasegawa (SH) test that compared the parsimony score of the inferred most parsimonious tree to one in which each branch was individually collapsed to a polytomy. ...
Gene loss can promote phenotypic differences between species, for example, if a gene constrains phenotypic variation in a trait, its loss allows for the evolution of a greater range of variation or even new phenotypes. Here, we explore the contribution of gene loss to the evolution of large bodies and augmented cancer resistance in elephants. We used genomes from 17 Afrotherian and Xenarthran species to identify lost genes, i.e., genes that have pseudogenized or been completely lost, and Dollo parsimony to reconstruct the evolutionary history of gene loss across species. We unexpectedly discovered a burst of gene losses in the Afrotherian stem lineage and found that the loss of genes with functions in regulated necrotic cell death modes was pervasive in elephants, hyraxes, and sea cows ( Paenungulata ). Among the lost genes are MLKL and RIPK3 , which mediate necroptosis, and sensors that activate inflammasomes to induce pyroptosis, including AIM2 , MEFV , NLRC4 , NLRP1 , and NLRP6 . These data suggest that the mechanisms that regulate necrosis and pyroptosis are either extremely derived or potentially lost in these lineages, which may contribute to the repeated evolution of large bodies and cancer resistance in Paenungulates as well as susceptibility to pathogen infection.
... Our findings provide direct evidence that a change in regulation, specifically the reduction in GAO expression, leads to the abolishment of costunolide biosynthesis. Importantly, a natural loss-of-function event is an essential part of the evolutionary landscape; however, previous investigations have primarily focused on the loss of protein-coding genes (Olson, 1999;Sharma et al., 2018;Hecker et al., 2019;Xu and Guo, 2020). Our study highlights that variations in the non-coding upstream region can also result in a reduction of gene expression and loss of function. ...
Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one.
... This was likely due to the loss or the modification of some genes or of gene networks utilized in marine animals for tissue and organ regeneration (Alibardi, 2022(Alibardi, , 2023a(Alibardi, , 2023b(Alibardi, , 2023c. Gene loss is one among other mechanisms that can determine new forms of adaptations, including in mammals (Sharma et al., 2018). ...
Regeneration varies largely among metazoans. Aside molecular processes, this epiphenomenon depends on the biological complexity and evolutive history of each species during the adaptation to their specific environment. While most species adapted to marine or freshwater conditions can extensively regenerate, those adapted to terrestrial conditions and parasitism lost the ability to regenerate. They are mainly represented from ascelmintes evolving eutely and numerous arthropods and amniotes. High regeneration can only occur in water‐adapted species and requires high tissue hydration, indirect development through metamorphosis and often also presence of asexual propagation. Metamorphosis allows the anatomical‐physiological transformation of a larva in an adult through an initial destructive phase followed by a constructive (regenerative) phase. Invertebrates and vertebrates that possess genomes including metamorphic genes can re‐utilize in part or largely similar genes for the regeneration of lost organs. I submit that during land adaptation in both invertebrates and vertebrates the initial larval stages and metamorphosis were lost or altered as some key genes, including those for telomerases, could no longer be expressed in the dry environment. Consequently, also the initial regenerative ability was lost while other epiphenomena were gained, including complex immunity and behaviour but also an evident process of ageing.
... Therefore, chemicals, such as alkaloids and terpenoids, in C. subcordata may be the main mechanism for disease defense on tropical coral islands, and MAPK may have reduced their role in defense. Keeping the balance between gene family expansion and contraction, which maintains the balanced allocation of energy sources, has also been observed in previous studies [52][53][54]. Considering no relevant studies have been carried out regarding C. subcordata, future studies are needed to confirm this in a laboratory setting. ...
Cordia subcordata trees or shrubs, belonging to the Boraginaceae family, have strong resistance and have adapted to their habitat on a tropical coral island in China, but the lack of genome information regarding its genetic background is unclear. In this study, the genome was assembled using both short/long whole genome sequencing reads and Hi–C reads. The assembled genome was 475.3 Mb, with 468.7 Mb (99.22%) of the sequences assembled into 16 chromosomes. Repeat sequences accounted for 54.41% of the assembled genome. A total of 26,615 genes were predicted, and 25,730 genes were functionally annotated using different annotation databases. Based on its genome and the other 17 species, phylogenetic analysis using 336 single-copy genes obtained from ortholog analysis showed that C. subcordata was a sister to Coffea eugenioides, and the divergence time was estimated to be 77 MYA between the two species. Gene family evolution analysis indicated that the significantly expanded gene families were functionally related to chemical defenses against diseases. These results can provide a reference to a deeper understanding of the genetic background of C. subcordata and can be helpful in exploring its adaptation mechanism on tropical coral islands in the future.
... Convergent evolution is a central theme in the history of life on Earth [1,2], and the products of convergence comprise a natural laboratory, complete with replicated experiments, for elucidating regions of the genome that underlie specific phenotypic traits [3][4][5]. Numerous definitions of convergent evolution have been proposed, but at their core, most center on the independent evolution of similar traits in multiple lineages [6]. Examples include the adaptive radiation of cichlid fishes that has resulted in multiple instances of convergence in body and trophic morphology [7]; the convergent evolution of fusiform bodies with similar control surfaces (i.e., fins, flippers, flukes) in various sharks, ichthyosaurs, and cetaceans [8]; convergence of elaborate territorial displays in Anolis lizards on different islands in the Caribbean [9]; and the classic case of convergent morphological evolution between assorted placental and marsupial mammals that includes wolves and thylacines, cats and quolls, anteaters and numbats, mice and marsupial mice, and between placental moles (golden moles, eulipotyphlan moles) and marsupial moles [1,10] ( Figure 1). ...
Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia’s aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis.
... Lachner et al. (2017) showed that cetaceans lack keratinocyte-differentiationassociated genes, including interleukin genes (IL36A, IL36B, IL37, IL37L, and IL38) and gasdermin genes (GSDMA, GSDMB, and GSDMC). Similarly, Sharma et al. (2018) found that cetaceans have lost hair-and epidermis-related genes such as desmoglein 4 (DSG4), desmocollin 1 (DSC1), transglutaminase 5 (TGM5), and GSDMA, and that arachidonate lipoxygenase 3 (ALOXE3), an important gene for skin barrier function, was lost after the splitting of the baleen and toothed whale lineages. Ehrlich et al. (2019) demonstrated that cetaceans have lost keratin 1 (KRT1) and keratin 10 (KRT10), which are crucial components of the cytoskeleton in the outer layers of the epidermis in terrestrial mammals. ...
Hair-related genes in mammals play important roles in the development and maintenance of hair and other keratinous structures in mammals. The peptidyl arginine deiminase 3 (PADI3) gene encodes an enzyme that catalyzes the conversion of arginine residues to citrulline. The S100 calcium binding protein A3 (S100A3) gene encodes a protein that is highly expressed in the hair cuticle and contains arginine residues that are converted to citrullines by PADI enzymes. In this study, we investigated the pseudogenization events of PADI3 and S100A3 in cetaceans and Hippopotamus amphibius. We found that PADI3 underwent three independent pseudogenization events during cetacean evolution, in baleen whales, toothed cetaceans other than Physeter catodon, and P. catodon. Notably, the entire PADI3 gene is absent in the baleen whales. Pseudogenization of S100A3 occurred independently in cetaceans and H. amphibius. Interestingly, we found that in cetaceans S100A3 underwent pseudogenization before PADI3, suggesting that differential selection pressures were acting on the two genes. Our findings provide valuable insights into the molecular evolution of these genes in cetaceans and hippopotamuses, highlighting their importance for understanding the evolution of hair-related genes.
... On the contrary, gene loss has been identified as an important feature throughout eukaryotic evolution, particularly during the origin of major lineages including animals and fungi (Fern andez & Gabald on, 2020;Guijarro-Clarke et al., 2020;Ocaña-Pallar es et al., 2022;Mer enyi et al., 2023). Predominantly, gene loss is considered a neutral process under the 'use it or lose it' model, in which genes that are no longer required are lost following the relaxation of selection (Albalat & Cañestro, 2016;Sharma et al., 2018). Conversely, it has also been argued that gene loss may facilitate adaptive evolution through a 'less is more' model (Albalat & Cañestro, 2016), where selection may promote the loss of genes associated with streamlining and simplification. ...
... The extent to which reduction is a neutral or adaptive process remains unclear and polarising the order of trait and gene loss may not be possible. Across eukaryotes, most gene loss events do not carry a strong functional signal, indicative of a neutral process (Domazet-Lo so et al., 2022) and in animal gene loss was seen to occur following a relaxation in selection (Sharma et al., 2018), although it has been proposed that gene loss in mycoheterotrophic orchids is proceeding faster than expected under a neutral process . Dynamics of gene family evolution in eukaryotes support a model of genome evolution, whereby genomic complexity evolved first, followed by lineagespecific reduction through gene loss as lineages evolve greater specialisation (Domazet-Lo so et al., 2022). ...
Plant evolution has been characterised by a series of major novelties in their vegetative and reproductive traits that have led to greater complexity. Underpinning this diversification has been the evolution of the genome. When viewed at the scale of the plant kingdom, plant genome evolution has been punctuated by conspicuous instances of gene and whole‐genome duplication, horizontal gene transfer and extensive gene loss. The periods of dynamic genome evolution often coincide with the evolution of key traits, demonstrating the coevolution of plant genomes and phenotypes at a macroevolutionary scale. Conventionally, plant complexity and diversity have been considered through the lens of gene duplication and the role of gene loss in plant evolution remains comparatively unexplored. However, in light of reductive evolution across multiple plant lineages, the association between gene loss and plant phenotypic diversity warrants greater attention.
... Our study identified nine members of the TLR family in silver pomfret: Patlr1, Patlr2, Patlr3, Patlr5, Patlr7, Patlr8, Patlr9, Patlr14 and Patlr21. Gene duplication is believed to have contributed significantly to biological diversity [44], while gene loss has been shown to be a universal source of genetic variation that aids adaptation [45]; V [46]. Both processes are critical in gene family formation and species evolution. ...
