Python Programming for Biology: Bioinformatics and Beyond

Homologues and species

When  comparing  different  versions  of  the  same  gene  or  protein,  say  in  a  multiple

alignment, the sequences analysed are all related to one another. Saying that they are the

same kind of gene is not only to say that they do the same job, but also that they have a

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common  ancestor.  Considering  all  the  species  of  mammals  on  Earth,  they  all  use

haemoglobin  to  transport  oxygen  via  blood  and  they  all  have  globin  genes  to  make  the

protein  part  of  this.  Thus  we  also  know  that  the  common  ancestor

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 of  mammals  had

haemoglobin particles and globin genes. The origins of globin undoubtedly go back even

further than this to the time when backboned animals were new to our planet. The globin

genes have diverged as the various species have split from one another, with any sequence

change being carried on to descendants of that line. Genes or proteins that are known to be

related  to  one  another  by  the  fact  that  they  share  a  common  ancestor  are  said  to  be

homologous. It is a common mistake to mix up sequence similarity with homology; it may

be  stated  that  you  can  ‘measure  sequence  homology’,  when  strictly  speaking  what  is

meant is that the sequences are sufficiently similar that we can infer homology: a common

ancestry.

Considering again the globin gene, as you may already know, there are even different

kinds of globin gene within a single genome. Normal haemoglobins are a combination of

alpha and beta versions of globin; two copies of each protein make the final particle. If we

consider  globins  that  are  used  in  an  embryo  and  fetus  even  more  globin  versions  are

present:  gamma,  delta,  epsilon,  zeta.  Each  version  comes  from  a  different  gene  and

because  they  are  so  similar  we  know  that  they  all  have  a  common  ancestor  and  were

generated by gene duplication  within  a  genome.  So  there  are  two  basic  means  by  which

homologues  are  generated:  when  species  separate  or  when  genes  duplicate.  Accordingly

for  a  pair  of  homologous  genes  or  proteins  we  can  say  whether  they  are  orthologues  or

paralogues.

Orthologues  are  different  versions  of  the  same  gene  in  different  species,  generated  by

the  fact  that  there  was  a  common  ancestor  which  also  had  the  gene.  For  closely  related

species this is usually a straightforward concept, but for more distantly related species the

definition  becomes  fuzzier,  given  that  functions  can  diverge  and  genes  can  be  copied

within an organism. For example, the human PAX6 gene (involved in formation of the iris

of the eye) has two orthologues in fruit fly,

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named eyeless (ey) and twin of eyeless (toy).

Paralogues are genes that are related by the fact that they arose from gene duplication

within  a  genome.  The  eyeless  and  twin  of  eyeless  genes  already  mentioned  are  good

examples; there was one ancestor gene and a duplication event generated the homologues.

This is not to say that the duplication occurred in the fruit fly we see today, but rather in

some  ancestor  that  gave  rise  to  many  species,  including  the  common  laboratory  fruit  fly

Drosophila. Looking at the globin genes where we have six close paralogues it is obvious

that here there must have been multiple gene duplication events.

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