List of unsolved problems in biology

• Origin of life. Exactly how and when did life on Earth originate? Which, if any, of the many hypotheses is correct? What were the metabolic pathways used by the earliest life forms?
  • Origins of viruses. Exactly how and when did different groups of viruses originate?
  • Extraterrestrial life. Might life which does not originate from planet Earth also have developed on other planets? Might this life be intelligent?
  • What are the chemical origins of life? How did non-living chemical compounds generate self-replicating, complex life forms?
• Evolution of sex. What selective advantages drove the development of sexual reproduction, and how did it develop?[1]
  • Homosexuality. What is the cause of homosexuality, especially in the human species?
• Development and evolution of brain. How and why did the brain evolve? What are the molecular determinants of individual brain development?
• Origin of Eukaryotes and Mitochondrial Migration How and why did the mitochondria enter the Eukaryotic Cell? Was this a biological miracle or was there some underlying cause that made the mitochondria likely to enter? How did the mitochondria's mitosis cycle come in sync with its host cell? Did the mitochondria or the nucleus develop first in eukaryotes? When exactly did these structures develop?

• Last Universal Common Ancestor What were the characteristics of the Last Universal Common Ancestor of Archaea, Bacteria, and Eukaryotes? Did Archaea and Eukaryotes evolve out of the domain Bacteria or to clade basal to it? Do Archaea and Eukaryotes share a later or earlier common ancestor to Bacteria?

• What do all the unknown proteins do? Almost two decades since the first eukaryotes were sequenced, the "biological role" of around 20% of proteins are still unknown.[2] Many of these proteins are conserved across most eukaryotic species and some are conserved in bacteria, indicating a role fundamental for life.[3][4][5]
• Determinants of cell size. How do cells determine what size to grow to before dividing?
• Golgi apparatus. In cell theory, what is the exact transport mechanism by which proteins travel through the Golgi apparatus?
• Mechanism of action of drugs. The mechanisms of action of many drugs including paracetamol, lithium, thalidomide and ketamine[6] are not completely understood.
• Protein folding. What is the folding code? What is the folding mechanism? Can we predict the native structure of a protein from its amino acid sequence? Is it possible to predict the secondary, tertiary and quaternary structure of a polypeptide sequence based solely on the sequence and environmental information? Inverse protein-folding problem: Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions?[7][8] This was achieved for several small globular proteins in 2008.[9] In 2020, it was announced that Google's AlphaFold, a neural network based on DeepMind artificial intelligence, is capable of predicting a protein's final shape based solely on its amino-acid chain with an accuracy of around 90% on a test sample of proteins used by the team.[10]
• Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?[11]
• RNA folding problem: Is it possible to accurately predict the secondary, tertiary and quaternary structure of a polyribonucleic acid sequence based on its sequence and environment?
• Protein design: Is it possible to design highly active enzymes de novo for any desired reaction?[12]
• Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[13]
• What is the mechanism of allosteric transitions of proteins? The concerted and sequential models have been hypothesised but neither has been verified.
• What are the endogenous ligands of orphan receptors?
• What substance is endothelium-derived hyperpolarizing factor?

• Why does biological aging occur? There are a number of hypotheses why senescence occurs including those that it is programmed by gene expression changes and that it is the accumulative damage of biological processes.
• Consistency of movement. How can we move so controllably, even though the motor nerve impulses seem haphazard and unpredictable?[14]
• How do organs grow to the correct shape and size?[15] How are the final shape and size of organs so reliably formed? These processes are in part controlled by the Hippo signaling pathway.
• Can developing biological systems tell the time?[15] To an extent, this appears to be the case, as shown by the CLOCK gene.
• Why are babies so rarely born with cancer?[16]

Unsolved problems relating to the interactions between organisms and their distribution in the environment include:

• Paradox of the plankton. The high diversity of phytoplankton seems to violate the competitive exclusion principle.

• Cambrian explosion. What is the cause of the apparent rapid diversification of multicellular animal life around the beginning of the Cambrian, resulting in the emergence of almost all modern animal phyla?

• Latitudinal diversity gradient. Why does biodiversity increase when going from the poles towards the equator?

• Darwin's abominable mystery of botany/plants. What is the exact evolutionary history of flowers and what is the cause of the apparently sudden appearance of nearly modern flowers in the fossil record?

• Absence of Loricifera fossils. There are at least 100 species of this phylum of marine dwelling animals (many undescribed), but none of them is known to be present in the fossil record.

• Adult form of Facetotecta. The adult form of this animal has never been encountered in the water, and it remains a mystery what it grows into.

• Origin of snakes. Did snakes evolve from burrowing lizards or aquatic lizards? There is evidence for both hypotheses.

• Origin of turtles. Did turtles evolve from anapsids or diapsids? There is evidence for both hypotheses.

• Ediacaran biota. How should Ediacaran biota be classified? Even what kingdom they belong to is unclear. Why were they so decisively displaced by Cambrian biota?

Unsolved problems relating to the behaviour of animals include:

• Homing. A satisfactory explanation for the neurobiological mechanisms that allow homing in animals has yet to be found.

• Flocking (behavior). How flocks of birds and bats coordinate their movements so quickly is not fully understood. Nor is the purpose of large flocks like those of starlings which seem to invite predators rather than protect them. [26]

• Butterfly migration. How do the descendants of monarch butterfly all over Canada and the US eventually, after migrating for several generations, manage to return to a few relatively small overwintering spots?

• Blue whale. There is not much data on the sexuality of the blue whale.[27]

• Gall wasp. It is largely unknown how gall wasps induce gall formation in plants; chemical, mechanical, and viral triggers have been discussed.

Unsolved problems relating to the structure and function of non-human organs, processes and biomolecules include:

• Alkaloids. The function of these substances in living organisms which produce them is not known[28]
• Korarchaeota (archaea). The metabolic processes of this phylum of archaea are so far unclear.
• Rotifer. What is the function of the retrocerebral organ of rotifers (pseudocoelomate animals)?
• Glycogen body. The function of this structure in the spinal cord of birds is not known.
• Arthropod head problem. A long-standing zoological dispute concerning the segmental composition of the heads of the various arthropod groups, and how they are evolutionarily related to each other.
• Ovaries of basking sharks. Only the right ovary in female basking sharks appears to function. The reason is unknown.
• Brightly colored bird eggs. It is unknown what evolutionary process would lead birds to having brightly colored eggs given the increased visibility to predators. [29]
• Stegosaur osteoderms/scutes. There is a long-standing debate over whether the primary function of the osteoderms/scutes of stegosaurs is protection from predators, sexual display, species recognition, thermoregulation, or other functions.