In this post, we’ll explore the core methods used in comparative genomics, the questions they help answer, and how they’re shaping our understanding of life.

1. Whole-Genome Alignment
Whole-genome alignment involves mapping the entire genome of one species to another. Tools like MUMmer, MAUVE, and LASTZ perform large-scale sequence alignments to detect conserved regions, rearrangements, insertions, and deletions.

Use Case:
Comparing human and chimpanzee genomes to identify evolutionary conserved sequences (ECS) and regions of divergence.

Key Challenges:
Handling repetitive sequences and genome rearrangements.

Computational complexity in large genomes.

2. Synteny and Collinearity Analysis
Synteny refers to conserved blocks of gene order across species. Tools like MCScanX, SynMap, or CHITRA (for visualizing synteny interactively) detect these blocks to understand chromosomal evolution.

Use Case:
Studying ancient genome duplications in plants.

Investigating chromosomal rearrangements in cancer genomes.

3. Ortholog and Paralog Detection
Orthologs are genes in different species that evolved from a common ancestor, while paralogs are genes duplicated within a genome. Identifying them is crucial for functional annotation and evolutionary studies.

Popular Tools:
OrthoFinder, Orthologous MAtrix (OMA), InParanoid, and EggNOG.

Use Case:
Functional prediction of uncharacterized genes based on orthologs in model organisms.

Tracing gene family evolution.

4. Phylogenomic Analysis
Phylogenomic methods combine phylogenetics and genomics to infer evolutionary trees based on genome-wide data. These methods can handle dozens to hundreds of genomes, using concatenated alignments or gene trees.

Tools:
RAxML, IQ-TREE, ASTRAL, Phylip, BEAST.

Use Case:
Resolving the evolutionary relationships between microbial species.

Studying speciation events.

5. Pan-Genome Analysis
The pan-genome consists of the core genome (shared by all strains) and the accessory genome (strain-specific genes). This is especially popular in microbial genomics.

Tools:
Roary, Panaroo, BPGA, PGAP.

Use Case:
Understanding virulence factor diversity in E. coli.

Designing broad-spectrum vaccines.

6. Comparative Transcriptomics
Comparing transcriptomes across species or conditions reveals conserved and unique expression patterns. RNA-seq data can be mapped to reference genomes to identify orthologous expression profiles.

Use Case:
Comparing stress response in extremophiles and model species.

Studying conserved regulatory networks.

7. Functional Element Comparison
Beyond genes, comparative genomics also targets non-coding regions—enhancers, promoters, miRNAs. Conservation across species often implies functional importance.

Tools:
PhastCons, GERP, phyloP (based on multiple alignments).

Use Case:
Detecting conserved non-coding elements in vertebrates.

Studying regulatory divergence in human evolution.

8. Horizontal Gene Transfer (HGT) Detection
In microbes, genes often jump across species boundaries. Comparative genomics can detect HGT by identifying genes that defy the expected phylogenetic pattern.

Tools:
HGTector, DarkHorse, AlienHunter, SIGI-HMM.

Use Case:
Tracing antibiotic resistance genes.

Exploring microbial adaptability in extreme environments.

Final Thoughts
Comparative genomics is a powerful lens to observe the diversity and unity of life. With a broad toolkit—from aligners to orthology pipelines, phylogenetic engines to visualization tools—it allows scientists to ask big questions: How did genomes evolve? What makes species unique? Where do new genes come from?

Whether you're studying extremophiles, building better crops, or exploring human ancestry, comparative genomics offers the methods to connect the dots across the tree of life.

The project is on bacterial gene gain and loss and emerging pathogenicity, and is described in full here: https://www.ebi.ac.uk/research/postdocs/ebpods/projects/goldman-welch-2015 . The EMBL-EBI / Cambridge Computational Biomedical Postdoctoral (“EBPOD”)

The closing date for applications is 3 September 2015. Nick Goldman EMBL-European Bioinformatics Institute Nick Goldman

More at https://www.ebi.ac.uk/research/postdocs/ebpods/projects/goldman-welch-2015

The fate of a cell is ultimately the product of the regulation of its genes. Gene regulation is a coordinated process acting at multiple levels of which transcription and translation are the most prominent. The Valen group is dedicated to the fundamental question of how transcription and translation is integrated to obtain the desired protein abundance. The recent development of high-throughput next generation sequencing techniques to monitor both active translation and transcription has made it possible to study this connection at the genome scale.

This project aims to elucidate the links between regulation of translation and transcription. The applicant will analyze next generation sequencing data and model gene regulation on a genome-wide level to identify the features that affect the translational output of transcripts. The work will be done in close collaboration with experimental scientists who will test the predictions of the computational models.

Additional information on the position can be obtained by contacting Eivind Valen (eivind.valen@ii.uib.no).

The research fellow must take part in the University’s approved PhD program leading to the degree within a time limit of 3 years. Application for admission to the PhD program, including a project plan outline for the training module, will be worked out in collaboration with the research group in question.

In total, the fellowship period is 4 years, 25 % of this will be allocated to teaching and/or administrative duties. The fellowship period may be reduced if the successful applicant has held previous employment as a research fellow or similar.

http://www.jobbnorge.no/en/available-jobs/job/102235/research-fellow-phd-candidate-in-computational-biology-2-positions

About 8,000 years ago, the gene EGLN1 changed by a single DNA base pair. Today, a relatively short time later on the scale of human history, 88 percent of Tibetans have the genetic variation, and it was virtually absent from closely related lowland Asians. The findings indicate the genetic variation endows its carriers with an advantage.

In those without the adaptation, low oxygen caused their blood to become thick with oxygen-carrying red blood cells, an attempt to feed starved tissues, which could cause long-term complications such as heart failure. The researchers found that the newly identified genetic variation protected Tibetans by decreasing the over-response to low oxygen.

Reference: http://www.nature.com/nature/journal/v512/n7513/abs/nature13408.html

http://katjulab.com/research.html

http://genome.crg.es/courses/Bioinformatics2003_genefinding/

Address of the bookmark: http://genome.crg.es/courses/Bioinformatics2003_genefinding/

Orthology relations can be used to transfer annotations from one gene (or protein) to another. Hence, detecting orthology relations has become an important task in the post-genomic era. Various genomic events, such as duplication and horizontal gene transfer, can cause erroneous assignment of orthology relations. In closely-related species, gene neighborhood information can be used to resolve many ambiguities in orthology inference. Here we present OrthoGNC, a software for accurately predicting pairwise orthology relations based on gene neighborhood conservation. Analyses on simulated and real data reveal the high accuracy of OrthoGNC. In addition to orthology detection, OrthoGNC can be employed to investigate the conservation of genomic context among potential orthologs detected by other methods. OrthoGNC is freely available online at http://bs.ipm.ir/softwares/orthognc and http://tinyurl.com/orthoGNC.

http://www.comp.nus.edu.sg/~wongls/projects/orthoGNC/

Address of the bookmark: http://www.sciencedirect.com/science/article/pii/S1672022917301663

There were ~910,000 requests made to BioGPS in 2016. Requests to BioGPS peaked in March and at the lowest in December.

Address of the bookmark: http://biogps.org/

11/3/2019: V 0.61, Improve graphical visualization (thanks to reviewers). Interactive networks and much more.

5/20/2019: V.0.60, Annotation database updated to Ensembl 96. New bacterial and fungal genomes based on STRING-db! Just paste your gene list to get enriched GO terms and othe pathways for over 315 plant and animal species, based on annotation from Ensembl (Release 96), Ensembl plants (R. 43) and Ensembl Metazoa (R. 43). An additional 2031 genomes (including bacteria and fungi) are annotated based on STRING-db (v.10). In addition, it also produces KEGG pathway diagrams with your genes highlighted, hierarchical clustering trees and networks summarizing overlapping terms/pathways, protein-protein interaction networks, gene characterristics plots, and enriched promoter motifs. 

Address of the bookmark: http://bioinformatics.sdstate.edu/go/

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AGORA is used to generate ancestral genomes for the Genomicus online server for gene order comparison, and has been in constant use in the group since.

Address of the bookmark: https://github.com/DyogenIBENS/Agora