Sansrity Sinha ; If your QUEST is to find out , which Mitofusin is the “ANCHESTRAL ONE” evolutionary vise , you can find it out or select the best candidate” by “functional efficiency differences and intuition” – the research is done on this subject at this link http://jcs.biologists.org/content/117/26/6535.full

Let me go little details as you well know the subject ;

Mitofusins are GTPases can be thought of as molecular clocks for the timing and specificity of events that take place within the cell .GTP (guanine triphosphate) and undergo a conformational change as GTP is hydrolyzed to GDP (guanine diphosphate) in the presence of a Mg2+ ion.

These GTPases in control of mitochondrial fusion are well conserved between mammals, flies, and yeast. Specific mitochondrial membrane-anchored dynamin family members mediate fusion between mitochondrial outer membranes known as Mfn1 and Mfn2. These two proteins are mitofusins contained within humans, that can alter the morphology of affected mitochondria in over-expressed conditions.

Mitofusin 1 is on Chromosome Number 3 in Humans http://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg19&position=chr3:179065480-179112719#hgTracks?db=hg19&position=chr3%3A179065480-179112719&hgsid=431826043_RO0GQF0kANHX6weaY1ZOuJf1saEH&_suid=143464570317107884371080427048

And Mitofusin 2 located on Chromosome Number 1 in Humans .http://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg19&position=chr1:12040238-12073571#hgTracks?db=hg19&position=chr1%3A12040238-12073571&hgsid=431826165_nlMp2GAm3shZlaxI8keuDjTRWAJp&_suid=143464580000407903637832244384

What it means is ; from the primitive Yeast to the Human Beings we see these “genes” on the Nuclear Chromosomes rather than on the Mitochondrial genes . They should be very ancient evolutionary vise , as ancient as the first ever “symbiotic relationship” in between Mitochondria and Eukaryotic cells , mitochondria as you know are the remnants of ancient, “facultative aerobic ” bacterial intruders now surviving as highly symbiotic . In fact mitomucin 1 and mitomucin 2 “ might have Different” functions ? and the functional division of the two Mfn proteins are unknown http://jcs.biologists.org/content/117/26/6535.full BUT Purified recombinant Mfn1 exhibited ∼eightfold higher GTPase activity than Mfn2. These findings indicate that the two Mfn proteins have distinct activities, and suggest that Mfn1 is mainly responsible for GTP-dependent membrane tethering.Which is the fundamental function needed in Symbiotic relationship ..! Evolutionary vise what it means , Mitofusin 1 may well be the one –Evolved first – because of “ HIGHER EFFICIENCY” both are highly conserved as well – simply because of 8 fold higher GTPase activity .. You may not find the answers through laborious phylogenetic tree construction because of the similarities of both molecules ...

For the BIC selection Question in order to fit the model , Lower (smaller) the BIC better the fit for phylogenetic data construction . Detailed info at the link

BICi is = –2loge Li + NiLoge n ,where n is the sample size(sequence length) ,the smaller the BIC ,the better the fit of the model to the data ..

http://sysbio.oxfordjournals.org/content/50/4/580.full.pdf+html

Let me add , one other important intuitive “evolutionary clue “ regarding your question of which Mitofusin isoform ( 1 or 2 ) is the ANCESTRAL one is ; the Cellular differentiation of higher life forms –particularly mammals- and “selective expression of Mitofusin 2 isotype at Heart, Skeletal and Neuronal cells which is primarily associated with “higher energy generation and oxygen consumption” and kinetic- locomotion- function of Mfn2 at the higher life forms . This –tissue specific (Heart,muscle,neuronal) preferential expression and association of Mfn2 also suggest not only higher energy generation and higher O2 consumption of fused Mitochondrial forms BUT also higher availability of Atmospheric Oxygen - which occurred later in evolutionary times- ..

http://jcs.biologists.org/content/116/13/2763.long Mfn2 isotype which was expressed mainly in heart and skeletal muscle.

http://ac.els-cdn.com/S0092867413010945/1-s2.0-S0092867413010945-main.pdf?_tid=0c133c6a-15f2-11e5-9631-00000aab0f01&acdnat=1434656683_36e83c35a78af7efa958c5964dfd2f91 Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance

http://hmg.oxfordjournals.org/content/21/22/4827.full.pdf Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons

ok..thank you so much for such a detailed explanation.  considering the tissue specific expression patterns of both genes Mfn1 indeed seems to be the ancestral one. but there is a difference of 18 amino acids in both genes. mfn1 is shorter by 18 amino acids than mfn2.  the difference lies in N terminal. I should check the motifs present in those 18amino acids..that would probably answer the relevance of 18 amino acids. thanky ou so much again.

Sansrity , You may find –similar- but not exact evolutionary pattern of DOMAIN DUPLICATION + ADDITION , I attached the similar research ( * ) you are conducting was done on Aspartate Racemase (AspR) evolution of its iso form ..

As clearly stated in this (* ) research's Discussion section “ High sequence similarity is sufficient evidence for the common ancestor and high structural and functional similarity is also generally accepted as evidence for distant homology between proteins that lack significant sequence similarity . If high sequence homology is available as well as high structural and functional similarity, it can be asserted that these proteins were evolved from a common ancestor. This rule can be safely applied to domains. In this evolutional way, gene duplication and gene fusion played primarily crucial roles .”

In your case Sansrity Sinha ...Addition of 18 more amino acids at N- Terminal of Mitofuscin I molecule and creation of Mitofuscin 2 molecule , is in fact further convincing –proof- that the addition had occurred at later time since the structure of the C end (proximal) portion of both Mitofuscin I and 2 are very similar . –Addition to the ANCESTRAL DOMAIN could have had occurred proximal –distal or at the middle theoretically as in the case of Aspartate Racemase the addition was at the C –end of the molecule – .. This N –terminal addition of Mitofuscin 2 , quite certainly represents the “Extra and Different higher efficiency function ADDED as needed by the “host cell” at later evolutionary times , to the primary function of Mitofuscin I to increase its “efficiency” for higher energy demand by the HOST symbiotic cell of facultative aerobe mitochondrial intruder at HIGHER O2 available atmosphere as well as “water dissolved O2” of early planet earth . What it means Sansrity , Evolution of photosynthetic prokaryotes(**) and -dramatic –sudden and Stepwise-increase of available O2 should coincide by the evolution of Mitofuscin 2 (addition of 18 N-terminal amino acids to the Ancestral Molecule of Mitofuscin 1 ) . When we go further evolutionary details and “search for efficient O2 producers- sudden and stepwise increase of Atmospheric O2 evolutionary event - (like Cyanobacteria evolution) what we find is : Green non-sulphur bacteria such as Cf. aurantiacus, which contains a pheophytin-quinone type of reaction center , have evolved very early. Thus, these photosynthetic green organisms existed long before the evolution of cyanobacteria (efficient O2 producers) and stepwise –sudden O2 increase .

What it means , our facultative aerobe mitochondrial SYMBIOTIC intruder’s HOST cells might have evolved Mitofuscin 1 molecule at this earlier period –before the Cyanobacteria evolution- “ and Mitofuscin 2 evolution might have –COINCIDED WITH- the evolution of Cyanobacteria –efficient O2 producers .

If you read the (**) evolutionary history of photosynthetic prokaryotes –lateral gene transfer and speciation- occurred that speciation events also represent the times of –Stepwise increase of available atmospheric and dissolved O2 early earth’s evolutionary history .

If we find that specific evolutionary period that represents – Stepwise and sudden increase of Atmospheric O2 –Cyanobacteria evolution time – that time period should also represent the Evolutionary time of Mitofuscin 2 from Mitofuscin I ...

As you clearly see Sansrity , by simple intuition and logic , looking into the “ Differences of efficiency and function and current mammalian cells differential tissue expression of Mitofuscin 1 and 2 as well as Nuclear Chromosomal differential location of individual genes at the Host cell “ without any “Phylogenetic calculation whatsoever” we may have –accurate hypothesis – and “prediction” and anticipation for the Time of Origination of the Molecule of Mitofuscin 2 from the Ancestral Mitofuscin 1 ...Simply because evolution of molecules (and their function) has “always” accompanied by –other changing events in the environment , nothing –no molecule(gene) has had ever evolved without a cause and effect among living beings .

(* ) http://www.sciencedirect.com/science/article/pii/S0014579302032647?np=y

( **) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693105/pdf/12594930.pdf

( ***) http://www.ncbi.nlm.nih.gov/pubmed/10361294