Protein length in eukaryotic and prokaryotic proteomes
Open accessAbstract
We analyzed length differences of eukaryotic, bacterial and archaeal proteins in relation to function, conservation and environmental factors. Comparing Eukaryotes and Prokaryotes, we found that the greater length of eukaryotic proteins is pervasive over all functional categories and involves the vast majority of protein families. The magnitude of these differences suggests that the evolution of eukaryotic proteins was influenced by processes of fusion of single-function proteins into extended multi-functional and multi-domain proteins. Comparing Bacteria and Archaea, we determined that the small but significant length difference observed between their proteins results from a combination of three factors: (i) bacterial proteomes include a greater proportion than archaeal proteomes of longer proteins involved in metabolism or cellular processes, (ii) within most functional classes, protein families unique to Bacteria are generally longer than protein families unique to Archaea and (iii) within the same protein family, homologs from Bacteria tend to be longer than the corresponding homologs from Archaea. These differences are interpreted with respect to evolutionary trends and prevailing environmental conditions within the two prokaryotic groups.
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The average protein length in budding yeast, fission yeast, and human cells is 400 amino acids per protein.
“In Escherichia coli and other bacteria, we use an average protein length, laa, of 300 aa/protein and in budding yeast, fission yeast, and human cells, we adopt the value of 400 aa/protein (where values are rounded to within about 10–20% accuracy).”
From What is the total number of protein molecules per cell volume? A call to rethink some published values (2013) · cites this paper as [22]
The Results (‘Protein lengths across proteomes’; page unavailable) report a median of 361 amino acids across five eukaryotic species, broadly consistent with a rounded estimate of 400. The paper reports medians rather than an average of 400, and the available passages do not establish that estimate separately for budding yeast, fission yeast, and humans. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe average protein length in E. coli and other bacteria is 300 amino acids per protein.
“In Escherichia coli and other bacteria, we use an average protein length, laa, of 300 aa/protein and in budding yeast, fission yeast, and human cells, we adopt the value of 400 aa/protein (where values are rounded to within about 10–20% accuracy).”
From What is the total number of protein molecules per cell volume? A call to rethink some published values (2013) · cites this paper as [22]
The Results section, “Protein lengths across proteomes” (page unavailable), reports a bacterial median of 267 amino acids, which is within the citing sentence’s stated 10–20% rounding tolerance of 300. It reports a median rather than an average and does not establish a value specifically for E. coli. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe median length of a human protein is 375 amino acids.
“the median length of a human protein is only 375 amino acids. 27”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [27]
The Results section (‘Protein lengths across proteomes’; page unavailable) reports a median of 361 amino acids for the pooled eukaryotic proteins, not a human-specific median. The Methods section (‘Proteomes’; page unavailable) says human proteins were included, but searches for ‘375’ and ‘Homo sapiens Table 2 median’ found no passage in our copy giving the claimed human value. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Brocchieri, L.
- Affiliations
- Stanford University (US)
- Corresponding author
- Brocchieri, L.
- ORCID
- Brocchieri, L.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-02
- Volume
- 33
- Issue
- 10
- Pages
- 3390-3400
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1150220
- OpenAlex
- W2142961247
- Cited by
- 414
- References
- 25
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 16 · 2023: 25 · 2022: 26 · 2021: 22 · 2020: 30 · 2019: 19 · 2018: 19 · 2017: 39 · 2016: 21 · 2015: 29 · 2014: 23 · 2013: 22 · 2012: 21
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Nucleic Acids Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM010452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protist diversity and phylogeny
- Keywords
- protein length, eukaryotic proteomes, bacterial proteome, archaeal proteome, protein domain fusion, multidomain proteins, protein family evolution, protein conservation, environmental adaptation
- MeSH terms
- Amino Acid Sequence, Animals, Bacterial Proteins, Eukaryotic Cells, Humans, Protein Structure, Tertiary, Evolution, Molecular, Archaeal Proteins, Proteome, Proteomics
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