Fitch2000

CREATED: 200904071119 LINK: url:~/Modules/Literature/Fitch2000.pdf Title: Homology: a personal view of some problems

Homology is the relationship of two characters that have descended, usually with divergence, from a common ancestral character. Characters can be nay genic, structural or behavioral feature of an organism.

Analogy: characters although similar have descended convergently from unrelated ancestral characters.

character/character-state: homology resides in the characters, not in their states

recognition of homology: one should not define homology objectively because

• it requires defining homology by an arbitrary amount of identity
• it exlcudes the possibility of analogy
• this still does not solve the problem of our confidence that characters
• asserted to be homologous do have a common ancestor

Homology is indivisible, you are either homologous or you are not.

** Subtypes of homology Orthology is that relationship where sequence divergence follows speciation, where the common ancestor of the two genes lies in the cenancestor (most recent commmon ancestor) of the taxa from which the two sequences were obtained

Paralogy is defined as that condition where sequence divergence follows gene duplication. Such genes might descend and diverge while existing side by side in the same lineage.

Xenology is the condition where the history of the gene involves an interspecies transfer of genetic material

The nature of the subtype relationship depends solely on whether the cenancestral sequence occurs at speciation or a duplication event.

Whenever a pair of paralogous genes are both orthologous to a more distant gene

• and they diverge such that one form retains the old function while the other acquires a new function - to label the pair of orthologs retaining the same funcftion as isorthologs.

** Gene loss problem Image that a gene duplicated and then, following a subsequent speciation, one lineage lost one gene and the second lineage lost the other gene. What is the relationship between the remaining two genes? Paralogy, of course. Gaps in an alignment can be considered to be a homolog, one of the states of characters could be ‘deleted’.

** Separating homology from analogy Possible if one has access to the ancestral sequences. If the similarity of the ancestral sequences are more alike than today’s sequences, the genes are homologous, else they are analogous.

** Gene conversion problem Consider a gene duplication creating paralogs, followed by a speciation event and then by gene conversions in which copies of blocks of DNA from one gene simply replaces the homologous residues in its paralog. Although they continue to look like paralogs within a species, they will appear to have duplicated recently and independently in each species. This can only be detected by reference to the surrounding sequences.

** Recombination problem A gene can be constructed from the domains of several other different genes. Not all part of a gene have the same history and this, in such cases, the gene is not the unit to which the terms orthology, paralogy, etc apply.

** Tandem repetitive characters problem Gap can be due to there being different number of repeats.

** Gene/Allele problem Are two alleles paralogs? No, given that the definition includes gene duplication.