The genomics of mimicry: Gene expression throughout development provides insights into convergent and divergent phenotypes in a Müllerian mimicry system.

A common goal in evolutionary biology is to discern the mechanisms that produce the astounding diversity of morphologies seen across the tree of life. Aposematic species, those with a conspicuous phenotype coupled with some form of defence, are excellent models to understand the link between vivid colour pattern variations, the natural selection shaping it, and the underlying genetic mechanisms underpinning this variation. Mimicry systems in which species share a conspicuous phenotype can provide an even better model for understanding the mechanisms of colour production in aposematic species, especially if comimics have divergent evolutionary histories. Here we investigate the genetic mechanisms by which mimicry is produced in poison frogs. We assembled a 6.02-Gbp genome with a contig N50 of 310 Kbp, a scaffold N50 of 390 Kbp and 85% of expected tetrapod genes. We leveraged this genome to conduct gene expression analyses throughout development of four colour morphs of Ranitomeya imitator and two colour morphs from both R. fantastica and R. variabilis which R. imitator mimics. We identified a large number of pigmentation and patterning genes differentially expressed throughout development, many of them related to melanophores/melanin, iridophore development and guanine synthesis. We also identify the pteridine synthesis pathway (including genes such as qdpr and xdh) as a key driver of the variation in colour between morphs of these species, and identify several plausible candidates for colouration in vertebrates (e.g. cd36, ep-cadherin and perlwapin). Finally, we hypothesise that keratin genes (e.g. krt8) are important for producing different structural colours within these frogs.

The complete sequence and comparative analysis of ape sex chromosomes.

Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements-owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.

The Complete Sequence and Comparative Analysis of Ape Sex Chromosomes.

Apes possess two sex chromosomes-the male-specific Y and the X shared by males and females. The Y chromosome is crucial for male reproduction, with deletions linked to infertility. The X chromosome carries genes vital for reproduction and cognition. Variation in mating patterns and brain function among great apes suggests corresponding differences in their sex chromosome structure and evolution. However, due to their highly repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the state-of-the-art experimental and computational methods developed for the telomere-to-telomere (T2T) human genome, we produced gapless, complete assemblies of the X and Y chromosomes for five great apes (chimpanzee, bonobo, gorilla, Bornean and Sumatran orangutans) and a lesser ape, the siamang gibbon. These assemblies completely resolved ampliconic, palindromic, and satellite sequences, including the entire centromeres, allowing us to untangle the intricacies of ape sex chromosome evolution. We found that, compared to the X, ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements. This divergence on the Y arises from the accumulation of lineage-specific ampliconic regions and palindromes (which are shared more broadly among species on the X) and from the abundance of transposable elements and satellites (which have a lower representation on the X). Our analysis of Y chromosome genes revealed lineage-specific expansions of multi-copy gene families and signatures of purifying selection. In summary, the Y exhibits dynamic evolution, while the X is more stable. Finally, mapping short-read sequencing data from >100 great ape individuals revealed the patterns of diversity and selection on their sex chromosomes, demonstrating the utility of these reference assemblies for studies of great ape evolution. These complete sex chromosome assemblies are expected to further inform conservation genetics of nonhuman apes, all of which are endangered species.

An unsupervised deep learning framework for predicting human essential genes from population and functional genomic data.

BACKGROUND: The ability to accurately predict essential genes intolerant to loss-of-function (LOF) mutations can dramatically improve the identification of disease-associated genes. Recently, there have been numerous computational methods developed to predict human essential genes from population genomic data. While the existing methods are highly predictive of essential genes of long length, they have limited power in pinpointing short essential genes due to the sparsity of polymorphisms in the human genome. RESULTS: Motivated by the premise that population and functional genomic data may provide complementary evidence for gene essentiality, here we present an evolution-based deep learning model, DeepLOF, to predict essential genes in an unsupervised manner. Unlike previous population genetic methods, DeepLOF utilizes a novel deep learning framework to integrate both population and functional genomic data, allowing us to pinpoint short essential genes that can hardly be predicted from population genomic data alone. Compared with previous methods, DeepLOF shows unmatched performance in predicting ClinGen haploinsufficient genes, mouse essential genes, and essential genes in human cell lines. Notably, at a false positive rate of 5%, DeepLOF detects 50% more ClinGen haploinsufficient genes than previous methods. Furthermore, DeepLOF discovers 109 novel essential genes that are too short to be identified by previous methods. CONCLUSION: The predictive power of DeepLOF shows that it is a compelling computational method to aid in the discovery of essential genes.

The genomics of mimicry: Gene expression throughout development provides insights into convergent and divergent phenotypes in a Müllerian mimicry system.

A common goal in evolutionary biology is to discern the mechanisms that produce the astounding diversity of morphologies seen across the tree of life. Aposematic species, those with a conspicuous phenotype coupled with some form of defence, are excellent models to understand the link between vivid colour pattern variations, the natural selection shaping it, and the underlying genetic mechanisms underpinning this variation. Mimicry systems in which multiple species share the same conspicuous phenotype can provide an even better model for understanding the mechanisms of colour production in aposematic species, especially if comimics have divergent evolutionary histories. Here we investigate the genetic mechanisms by which vivid colour and pattern are produced in a Müllerian mimicry complex of poison frogs. We did this by first assembling a high-quality de novo genome assembly for the mimic poison frog Ranitomeya imitator. This assembled genome is 6.8 Gbp in size, with a contig N50 of 300 Kbp R. imitator and two colour morphs from both Ranitomeya fantastica and R. variabilis which R. imitator mimics. We identified a large number of pigmentation and patterning genes that are differentially expressed throughout development, many of them related to melanocyte development, melanin synthesis, iridophore development and guanine synthesis. Polytypic differences within species may be the result of differences in expression and/or timing of expression, whereas convergence for colour pattern between species does not appear to be due to the same changes in gene expression. In addition, we identify the pteridine synthesis pathway (including genes such as qdpr and xdh) as a key driver of the variation in colour between morphs of these species. Finally, we hypothesize that genes in the keratin family are important for producing different structural colours within these frogs.

Signal, bias, and the role of transcriptome assembly quality in phylogenomic inference.

BACKGROUND: Phylogenomic approaches have great power to reconstruct evolutionary histories, however they rely on multi-step processes in which each stage has the potential to affect the accuracy of the final result. Many studies have empirically tested and established methodology for resolving robust phylogenies, including selecting appropriate evolutionary models, identifying orthologs, or isolating partitions with strong phylogenetic signal. However, few have investigated errors that may be initiated at earlier stages of the analysis. Biases introduced during the generation of the phylogenomic dataset itself could produce downstream effects on analyses of evolutionary history. Transcriptomes are widely used in phylogenomics studies, though there is little understanding of how a poor-quality assembly of these datasets could impact the accuracy of phylogenomic hypotheses. Here we examined how transcriptome assembly quality affects phylogenomic inferences by creating independent datasets from the same input data representing high-quality and low-quality transcriptome assembly outcomes. RESULTS: By studying the performance of phylogenomic datasets derived from alternative high- and low-quality assembly inputs in a controlled experiment, we show that high-quality transcriptomes produce richer phylogenomic datasets with a greater number of unique partitions than low-quality assemblies. High-quality assemblies also give rise to partitions that have lower alignment ambiguity and less compositional bias. In addition, high-quality partitions hold stronger phylogenetic signal than their low-quality transcriptome assembly counterparts in both concatenation- and coalescent-based analyses. CONCLUSIONS: Our findings demonstrate the importance of transcriptome assembly quality in phylogenomic analyses and suggest that a portion of the uncertainty observed in such studies could be alleviated at the assembly stage.