We've had "dark matter," the "dark web" and now, (gasp) "The Dark Proteome."

[NNadir]

I came across this paper and found some of the locutions therein both amusing in interesting. (I love subjects involving terms about which I know nothing.)

Intrinsically Disordered Proteins: Critical Components of the Wetware Prakash Kulkarni, Supriyo Bhattacharya, Srisairam Achuthan, Amita Behal, Mohit Kumar Jolly, Sourabh Kotnala, Atish Mohanty, Govindan Rangarajan, Ravi Salgia, and Vladimir Uversky Chemical Reviews 2022 122 (6), 6614-6633.

It contains this language:

1.1. Dark Matter in Biology

The plethora of proteins from all of the extinct and extant organisms is defined as the protein universe, a concept introduced by István Ladunga in the 1990s. (1) While a significant fraction of the protein universe is well-studied and the structures of thousands of proteins have been determined, the nature of the remainder of this universe remains poorly understood. The latter fraction of proteins with unknown structures is referred to as the dark proteome, which is a constituent of the biological dark matter. (2) Indeed, significant fractions of the proteomes of archaea and bacteria, and almost half of the eukaryotic and viral proteomes, are estimated to be dark. (3) Like the dark matter in the physical universe, the dark matter in biology is not easily detectable by the traditional approaches of structural biology. However, the dark matter is essential to life, is involved in performing functions that are perceptible, and complements the functions performed by their ordered (visible) counterparts.

Several computational studies on the molecular evolution of the protein universe (3?6) suggest that the protein universe is expanding, and proteins with common ancestors billions of years ago are diverging in their molecular composition. (7) Further, they also reveal that, within the dark proteome, even the foldable domains have specific features. For example, they are generally shorter in length and have unique distributions of hydrophobic residues when compared to known domain families. More importantly, the studies indicate that the constituents of the dark proteome exhibit a higher propensity for intrinsic disorder. (6) Indeed, intrinsically disordered proteins (IDPs) (and intrinsically disordered protein regions within ordered proteins, or IDPRs) that lack a 3-dimensional structure under physiological conditions (8?10) comprise a large fraction of the dark matter in the protein universe. (4,8,11?16)

Scary. Darkness.

I am trained to think of proteins, for good and for bad, as flexible and malleable but otherwise highly ordered. It looks like a fun paper; I should read it sometime.

[BadgerKid]

1. Transcriptomic and proteomic medicine are slowly coming, too.