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Novel phylogenetic methods are needed for understanding gene function in the era of mega-scale genome sequencing

Nagy, László G, Merényi, Zsolt, Hegedüs, Botond, Bálint, Balázs·2020·Nucleic Acids Research
DOI 10.1093/nar/gkz1241PMC PMC7049691
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Abstract

Ongoing large-scale genome sequencing projects are forecasting a data deluge that will almost certainly overwhelm current analytical capabilities of evolutionary genomics. In contrast to population genomics, there are no standardized methods in evolutionary genomics for extracting evolutionary and functional (e.g. gene-trait association) signal from genomic data. Here, we examine how current practices of multi-species comparative genomics perform in this aspect and point out that many genomic datasets are under-utilized due to the lack of powerful methodologies. As a result, many current analyses emphasize gene families for which some functional data is already available, resulting in a growing gap between functionally well-characterized genes/organisms and the universe of unknowns. This leaves unknown genes on the ‘dark side’ of genomes, a problem that will not be mitigated by sequencing more and more genomes, unless we develop tools to infer functional hypotheses for unknown genes in a systematic manner. We provide an inventory of recently developed methods capable of predicting gene-gene and gene-trait associations based on comparative data, then argue that realizing the full potential of whole genome datasets requires the integration of phylogenetic comparative methods into genomics, a rich but underutilized toolbox for looking into the past.

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  • For simple traits with easily quantifiable phenotypes and a simple genetic basis, PhyloG2P studies will have a chance to identify specific genotype-to-phenotype maps.

    “On one end, we can conceptualize “simple” traits with both easily quantifiable phenotypes and a simple genetic basis. Here PhyloG2P studies will have a chance to identify specific genotype to phenotype maps (Lamichhaney et al. 2019; Nagy et al. 2020; Okuyama et al. 2025).”

    From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Nagy et al. 2020

  • Utilizing replicated evolution provides a key advantage for discovering genotype-to-phenotype relationships even in genomic regions with no prior functional characterization.

    “It has also been noted that utilizing replicated evolution provides a key advantage for discovering genotype to phenotype relationships, even in genomic regions with no prior functional characterization (Nagy et al. 2020).”

    From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Nagy et al. 2020

  • The evolutionary perspective of PhyloG2P enables genotype to phenotype mapping in situations where typical population genetics approaches would be challenging, if not impossible to implement.

    “This evolutionary perspective enables genotype to phenotype mapping in situations where typical population genetics approaches would be challenging, if not impossible to implement (Nagy et al. 2020; Smith et al. 2020).”

    From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Nagy et al. 2020

  • As sequenced genomes rapidly increased in availability over the past 20 years, it became clear that there was a need for statistical analysis methods that could be applied genome-wide while maintaining low error rates.

    “However, as sequenced genomes rapidly increased in availability over the past 20 years, it became clear that there was a need for statistical analysis methods that could be applied genome-wide while maintaining low error rates (Nagy et al. 2020).”

    From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Nagy et al. 2020

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Metadata

Authors
Nagy, L. G., Merényi, Z., Hegedüs, B., & Bálint, B.
Affiliations
Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Temesvari krt 62. Szeged 6726, Hungary
ORCID
Nagy, László G
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2020-01-16
Volume
48
Issue
5
Pages
2209-2219
ISSN
  • 0305-1048
  • 1362-4962
DOI
10.1093/nar/gkz1241
PMC
PMC7049691
Cited by
43
References
9
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • European Research Council (758161)
  • Hungarian National Research (Ginop-2.3.2-15-00001)

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