Thousands of exoplanets are known to orbit nearby stars. Plans for the next generation of space-based and ground-based telescopes are fueling the anticipation that a precious few habitable planets can be identified in the coming decade. Even more highly anticipated is the chance to find signs of life on these habitable planets by way of biosignature gases. But which gases should we search for? Although a few biosignature gases are prominent in Earth's atmospheric spectrum (O ₂ , CH ₄ , N ₂ O), others have been considered as being produced at or able to accumulate to higher levels on exo-Earths ( e.g. , dimethyl sulfide and CH ₃ Cl). Life on Earth produces thousands of different gases (although most in very small quantities). Some might be produced and/or accumulate in an exo-Earth atmosphere to high levels, depending on the exo-Earth ecology and surface and atmospheric chemistry. To maximize our chances of recognizing biosignature gases, we promote the concept that all stable and potentially volatile molecules should initially be considered as viable biosignature gases. We present a new approach to the subject of biosignature gases by systematically constructing lists of volatile molecules in different categories. An exhaustive list up to six non-H atoms is presented, totaling about 14,000 molecules. About 2500 of these are CNOPSH compounds. An approach for extending the list to larger molecules is described. We further show that about one-fourth of CNOPSH molecules (again, up to N = 6 non-H atoms) are known to be produced by life on Earth. The list can be used to study classes of chemicals that might be potential biosignature gases, considering their accumulation and possible false positives on exoplanets with atmospheres and surface environments different from Earth's. The list can also be used for terrestrial biochemistry applications, some examples of which are provided. We provide an online community usage database to serve as a registry for volatile molecules including biogenic compounds. Key Words: Astrobiology—Atmospheric gases—Biosignatures—Exoplanets. Astrobiology 16, 465–485.

A long-term goal of exoplanet studies is the identification and detection of biosignature gases. Beyond the most discussed biosignature gas O₂, only a handful of gases have been considered in detail. In this study, we evaluate phosphine (PH₃). On Earth, PH₃ is associated with anaerobic ecosystems, and as such, it is a potential biosignature gas in anoxic exoplanets. We simulate the atmospheres of habitable terrestrial planets with CO₂- and H₂-dominated atmospheres and find that PH₃ can accumulate to detectable concentrations on planets with surface production fluxes of 10¹⁰ to 10¹⁴ cm⁻² s⁻¹ (corresponding to surface concentrations of 10s of ppb to 100s of ppm), depending on atmospheric composition and ultraviolet (UV) irradiation. While high, the surface flux values are comparable to the global terrestrial production rate of methane or CH₄ (10¹¹ cm⁻² s⁻¹) and below the maximum local terrestrial PH₃ production rate (10¹⁴ cm⁻² s⁻¹). As with other gases, PH₃ can more readily accumulate on low-UV planets, for example, planets orbiting quiet M dwarfs or with a photochemically generated UV shield. PH₃ has three strong spectral features such that in any atmosphere scenario one of the three will be unique compared with other dominant spectroscopic molecules. Phosphine's weakness as a biosignature gas is its high reactivity, requiring high outgassing rates for detectability. We calculate that tens of hours of JWST (James Webb Space Telescope) time are required for a potential detection of PH₃. Yet, because PH₃ is spectrally active in the same wavelength regions as other atmospherically important molecules (such as H₂O and CH₄), searches for PH₃ can be carried out at no additional observational cost to searches for other molecular species relevant to characterizing exoplanet habitability. Phosphine is a promising biosignature gas, as it has no known abiotic false positives on terrestrial planets from any source that could generate the high fluxes required for detection.

Little is known about the function of α-N methylation, an unusual post-translational modification in which the amino-terminal residues of proteins are methylated. One known example is that α-N methylation of the Ran guanine nucleotide-exchange factor RCC1 is required for its association with chromatin. More than 30 years ago, it was suggested that a eukaryotic α-N-specific methyltransferase might exist, and now one has been found in HeLa cells. Schaner et al. describe the first known α-N-methyltransferase, named N-terminal RCC1 methyltransferase (NRMT). They identify the NRMT recognition sequence and several new methylation targets, including the tumour suppressor proteins SET and retinoblastoma protein (Rb). A requirement for α-N-methylation is also shown in normal bipolar spindle formation and chromosome segregation. α-N-methylation is an unusual post-translational modification in which the amino-terminal residues of proteins are methylated. One example is the Ran guanine nucleotide-exchange factor, RCC1, which requires methylation for its association with chromatin. These authors describe the first α-N-methyltransferase, named N-terminal RCC1 methyltransferase (NRMT). They identify the NRMT recognition sequence and several new methylation targets, and demonstrate the importance of α-N-methylation for normal bipolar spindle formation and chromosome segregation. The post-translational methylation of α-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function or enzymology of this modification. Several other bacterial and eukaryotic proteins have since been shown to be α-N-methylated3,4,5,6,7,8,9,10. However, the Ran guanine nucleotide-exchange factor, RCC1, is the only protein for which any biological function of α-N-methylation has been identified3,11. Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects3,11, but further characterization of this modification has been hindered by ignorance of the responsible methyltransferase. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys, indicating that they may be targets of the same, unknown enzyme3,12. The initiating Met is cleaved, and the exposed α-amino group is mono-, di- or trimethylated. Here we report the discovery of the first α-N-methyltransferase, which we named N-terminal RCC1 methyltransferase (NRMT). Substrate docking and mutational analysis of RCC1 defined the NRMT recognition sequence and enabled the identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB. Knockdown of NRMT recapitulates the multi-spindle phenotype seen with methylation-defective RCC1 mutants3, demonstrating the importance of α-N-methylation for normal bipolar spindle formation and chromosome segregation.

Centromeres are chromosomal loci required for accurate segregation of sister chromatids during mitosis. The location of the centromere on the chromosome is not dependent on DNA sequence, but rather it is epigenetically specified by the histone H3 variant centromere protein A (CENP-A). The N-terminal tail of CENP-A is highly divergent from other H3 variants. Canonical histone N termini are hotspots of conserved posttranslational modification; however, no broadly conserved modifications of the vertebrate CENP-A tail have been previously observed. Here, we report three posttranslational modifications on human CENP-A N termini using high-resolution MS: trimethylation of Gly1 and phosphorylation of Ser16 and Ser18. Our results demonstrate that CENP-A is subjected to constitutive initiating methionine removal, similar to other H3 variants. The nascent N-terminal residue Gly1 becomes trimethylated on the α-amino group. We demonstrate that the N-terminal RCC1 methyltransferase is capable of modifying the CENP-A N terminus. Methylation occurs in the prenucleosomal form and marks the majority of CENP-A nucleosomes. Serine 16 and 18 become phosphorylated in prenucleosomal CENP-A and are phosphorylated on asynchronous and mitotic nucleosomal CENP-A and are important for chromosome segregation during mitosis. The double phosphorylation motif forms a salt-bridged secondary structure and causes CENP-A N-terminal tails to form intramolecular associations. Analytical ultracentrifugation of phospho-mimetic CENP-A nucleosome arrays demonstrates that phosphorylation results in greater intranucleosome associations and counteracts the hyperoligomerized state exhibited by unmodified CENP-A nucleosome arrays. Our studies have revealed that the major modifications on the N-terminal tail of CENP-A alter the physical properties of the chromatin fiber at the centromere.