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Sequencing multiple species that share the same ecological niche may be a new frontier for genomic studies. While such studies should shed light on molecular convergence, genomic-level analyses have been unsuccessful, due mainly to the absence of empirical controls. Woody plant species that colonized the global tropical coasts, collectively referred to as mangroves, are ideal for convergence studies. Here, we sequenced the genomes/transcriptomes of 16 species belonging in three major mangrove clades. To detect convergence in a large phylogeny, a CCS+ model is implemented, extending the more limited CCS method (convergence at conservative sites). Using the empirical control for reference, the CCS+ model reduces the noises drastically, thus permitting the identification of 73 convergent genes with Ptrue (probability of true convergence) > 0.9. Products of the convergent genes tend to be on the plasma membrane associated with salinity tolerance. Importantly, convergence is more often manifested at a higher level than at amino-acid (AA) sites. Relative to >50 plant species, mangroves strongly prefer 4 AAs and avoid 5 others across the genome. AA substitutions between mangrove species strongly reflect these tendencies. In conclusion, the selection of taxa, the number of species and, in particular, the empirical control are all crucial for detecting genome-wide convergence. We believe this large study of mangroves is the first successful attempt at detecting genome-wide site convergence.

The biological species concept (BSC) is the cornerstone of neo-Darwinian thinking. In BSC, species do not exchange genes either during or after speciation. However, as gene flow during speciation is increasingly being reported in a substantial literature, it seems time to reassess the revered, but often doubted, BSC. Contrary to the common perception, BSC should expect substantial gene flow at the onset of speciation, not least because geographical isolation develops gradually. Although BSC does not stipulate how speciation begins, it does require a sustained period of isolation for speciation to complete its course. Evidence against BSC must demonstrate that the observed gene flow does not merely occur at the onset of speciation but continues until its completion. Importantly, recent genomic analyses cannot reject this more realistic version of BSC, although future analyses may still prove it wrong. The ultimate acceptance or rejection of BSC is not merely about a historical debate; rather, it is about the fundamental nature of species – are species (and, hence, divergent adaptations) driven by a relatively small number of genes, or by thousands of them? Many levels of biology, ranging from taxonomy to biodiversity, depend on this resolution.

Structural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%–1.53%) compared to other East Asian genomes (0.70%–0.98%), reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a 662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

Food web and gene regulatory networks (GRNs) are large biological networks, both of which can be analyzed using the May–Wigner theory. According to the theory, networks as large as mammalian GRNs would require dedicated gene products for stabilization. We propose that microRNAs (miRNAs) are those products. More than 30% of genes are repressed by miRNAs, but most repressions are too weak to have a phenotypic consequence. The theory shows that (i) weak repressions cumulatively enhance the stability of GRNs, and (ii) broad and weak repressions confer greater stability than a few strong ones. Hence, the diffuse actions of miRNAs in mammalian cells appear to function mainly in stabilizing GRNs. The postulated link between mRNA repression and GRN stability can be seen in a different light in yeast, which do not have miRNAs. Yeast cells rely on non-specific RNA nucleases to strongly degrade mRNAs for GRN stability. The strategy is suited to GRNs of small and rapidly dividing yeast cells, but not the larger mammalian cells. In conclusion, the May–Wigner theory, supplanting the analysis of small motifs, provides a mathematical solution to GRN stability, thus linking miRNAs explicitly to ‘developmental canalization’.

Colorectal cancer is one of the most common malignancies and is the second leading cause of cancer death worldwide. Generally, there are three categories of colorectal cancer development mechanism—genetic, epigenetic and aberrant immunological signaling pathways—all of which may be initiated by an imbalanced gut microbiota. Epigenetic modifications enable host cells to change gene expression without modifying the gene sequence. The microbiota can interact with the host genome dynamically through the interface presented by epigenetic modifications. In particular, bacterially derived short-chain fatty acids have been identified as one clear link in the interaction of the microbiota with host epigenetic pathways. This review discusses recent findings relating to the cross talk between the microbiota and epigenetic modifications in colorectal cancer.

The human retina is a complex neural tissue that detects light and sends visual information to the brain. However, the molecular and cellular processes that underlie aging primate retina remain unclear. Here, we provide a comprehensive transcriptomic atlas based on 119,520 single cells of the foveal and peripheral retina of humans and macaques covering different ages. The molecular features of retinal cells differed between the two species, suggesting the distinct regional and species specializations of the human and macaque retinae. In addition, human retinal aging occurred in a region- and cell-type- specific manner. Aging of human retina exhibited a foveal to peripheral gradient. MYO9A− rods and a horizontal cell subtype were greatly reduced in aging retina, indicating their vulnerability to aging. Moreover, we generated a dataset showing the cell-type- and region- specific gene expression associated with 55 types of human retinal disease, which provides a foundation to understand the molecular and cellular mechanisms underlying human retinal diseases. Together, these datasets are valuable for understanding the molecular characteristics of primate retina, as well as the molecular regulation of aging progression and related diseases.

As far as we know, animal development is a process that is unique to our planet. That does not mean, however, that development beyond our realm is impossible. As it starts to become feasible for us to look to the sky for another place to call home, we may start to appreciate the gravity of this question. In this issue, Lei et al. investigate for the first time the repercussions of space travel on the first decisions made by mouse embryos. Developing a novel micro-incubator, capable of automatic micrography and fixation, harboring some 3400 two-cell embryos, they investigate the consequences of development after being projected into the stratosphere in the SJ-10 satellite [1].