SMBE Conference guidelines

Download a PDF of the Conference Guidelines here.

Statement of diversity

SMBE has a strong commitment to diversity. Organizers should place emphasis on diversity of participants, including gender and geographic diversity, at every level of the meeting, including but not limited to the selection of plenary speakers, symposium organizers, and invited and contributed talks. Please ensure that this criterion is considered throughout the organization of the conference.

Professional Conference Organizer (PCO)

Each conference is organized jointly by SMBE’s contracted Professional Conference Organizer (PCO) and the Local Organizing Committee.  The role of the PCO is described in its contract with SMBE.

Local Organizing Committee (LOC)

The SMBE conference Local Organizing Committee should include Local Organizers and one member of SMBE Council. The role of the Council member on the LOC is to make sure the conference organizers adhere to these guidelines. Additionally, one organizer of the meeting from a previous year and one organizer of the meeting for the next year should be included for the purpose of continuity.

The LOC will be required to sign a formal agreement with SMBE agreeing to its responsibilities.

The LOC should send any presentations it makes – usually their proposal and post-conference feedback – to the SMBE Executive Administrator for archiving.

Financing

It is very important that the meeting is fully costed, with costs borne by the meeting and not by the Society.  A rolling budget should be set up with precise costs and with frequent updates on income and expenditure. The Society will provide US$100,000, which is the only funding promised by the Society. While these funds can be made available at any time and used temporarily for other expenditures (such as reserving a venue), it is understood that the US$100,000 will ultimately cover travel costs for 50 invited speakers.  In addition, in the event that a short-term loan is required for down-payments on the venue and suppliers, then this can be arranged. Be aware that this loan will be issued in US dollars and all currency change costs, as well as the danger of currency fluctuations, must be borne by the conference.

Size of conference

The conference can currently expect between 1000 and 1500 delegates, although we have seen considerable fluctuations in this number depending on factors such as convenience and cost of travel. Organizers are advised to make two alternative plans for a smaller and a larger conference - i.e. make plans for a smaller conference but include options to expand if registration numbers seem to indicate the meeting will be large. This should happen at the same location with options for a larger auditorium that can hold the entire conference. Conference attendance should be capped at 2000.

Approximate timelines

When

What

Notes

Last day of the conference of the preceding year.

Initial website goes live

 

Includes:

●       venue

●       opportunities for sponsorship

●       composition of the organizing committee

●       contact information for the conference organizer.

10 months before the date of the conference.

Call for symposia opens

See ‘Call for symposia’ below.

9 months before the date of the conference

Call for symposia closes

 

8.5 months before the conference

Notification of successful Symposia

 

8 months before the conference

Titles and short description of all symposia, should be placed on the conference website. Note that these are sometimes worded differently from the original proposals, which sometimes contain information related to the submission process.,.

 

8 months before the conference

Early bird registration opens

This deadline offers discount on the registration fee. Past experience indicates that 50-75% of delegates will take advantage of this early registration deadline.

Early bird registration should be advertised to the society membership, in the society journals, through the social media, on EvolDir, etc.

7 months before the conference

Abstract submission and award applications open


6 months before the conference

Abstract submission and award applications close (though it is common to extend by one week, depending on number of submissions).

Fitch Symposium, Abstract and travel award deadlines all occur at the same time. Fitch finalists are selected first and present in a separate symposium.

2-3 weeks prior to council decision of travel awards

Deadline for symposium organizers’ talk selection

To allow inclusion of talks in symposia to be considered in selection of travel awards

2 weeks before early bird registration closes

Council decision of travel awards: award applicants notified of success or otherwise

This is essential to allow applicants time to register at Early Bird rate if they haven’t received a travel/registration award. Some individuals who do not receive funding or are not selected for a talk will not register. There can be loss of ~100 participants as a result.

4 months before the conference

Early bird registration closes, full price registration opens

 

2 months before the conference

Full programme available online


Until the conference begins

Full cost registration

Full cost online registration; allows delegates to submit an abstract, though as an additional encouragement to register early, it should be stipulated that late abstracts can be considered only for poster presentations.

Either on the penultimate day of the meeting or up to two days later

Post-meeting survey

To be emailed to all meeting participants and able to run on a computer OR phone 


Structure of the conference

Duration

The preferred conference length is at 3.5 days with the acceptable range from 3 to 4 days (not counting the day of the council meeting/opening reception). The LOC is encouraged but not required to organize Public Lectures on Evolution/Molecular Evolution either immediately before or immediately after the meeting.

Council meeting

One council meeting to be held in a room that accommodates the council plus outside participants (about 16 people altogether).  Light breakfast, lunch, and all day coffee, tea, and light refreshments should be provided. This meeting will usually take place on the first day of the conference, starting at 8 or 9 am and must end at least 15 minutes before the Nei lecture. The main conference usually begins in the late afternoon/early evening with the Nei lecture, followed by the opening reception.

Scientific content

Limit oral presentations per person

Each person is limited to one oral presentation (either invited or contributed) for the entire annual SMBE meeting. If the same person is invited to several symposia, the person is given a choice of in which symposium s/he would like to present.

Presenter information

Each presenter should have clear instructions on where their presentation is going to be held, when they have been allocated a speaking time, and how to upload their slides.

Plenary lectures

There should be 3-4 plenary lectures, which are attended by all delegates, and usually last one hour. The number of plenary lectures should be limited to keep costs down and maximize  the number of multi-speaker symposia. Refer to the ‘Statement of Diversity’ above in the selection of plenary speakers. 

One of these plenary lectures is the Nei Lecture, named in honour of Professor Masatoshi Nei, and is given by the President of the society. Usually this lecture takes place near the beginning of the conference. SMBE has funds for this lecture to be published in MBE. The other plenary lectures are invited by the LOC and the invitees are usually fully funded in terms of the registration fee, travel and accommodation by the meeting.

Special symposia

Fitch Symposium

The Fitch Symposium occurs as an exclusive event when no other events or symposia are taking place.

Graduate students and postdocs in their first year of their first postdoc are eligible to apply to present their work in the Fitch Symposium, which is a plenary symposium, again attended by all delegates at the conference. A committee is convened each year by the Past-President to select the 8 talks from the submitted abstracts. The President-Elect will moderate the Fitch Symposium. The President will convene a committee to select the winner.

Open Symposium

The LOC is strongly encouraged to include an Open Symposium at which ground-breaking work not covered by the accepted symposium topics can be presented, Faculty award recipients can present, and potentially to allow more student/postdoc talks accepted.

Faculty awards symposium

There may also be a separate symposium for recipients of the Allan Wilson, Margaret Dayhoff, Motoo Kimura, and Community Service Awards.  Recipients of these awards should all be given the opportunity at the meeting, either in an ordinary symposium, or the special symposium, or in slots set aside for them in the Open Symposium.  The Council members responsible for these awards should be informed of the latest dates that lectures can incorporated into the programme.

Parallel symposia

The LOC should have a (usually audible) mechanism to ensure that concurrent sessions stay on time and try to minimize similarity in content or theme of overlapping concurrent sessions.

Number of symposia

There should be approximately 20-30 symposia, usually with no more than four parallel sessions (fewer than four is fine). SMBE Council considers that if there are more than four parallel sessions then delegates feel they are missing too many talks, while fewer parallel sessions restrict the diversity of the conference. Moreover, recent experience has shown that more sessions and/or additional plenary speakers can put the meeting into financial jeopardy.

Call for symposia

The call for symposia should indicate that if a symposium is selected, the invited speakers will have all or most of their registration fee, accommodation, and travel covered by the conference (at the level of approximately $2000 per invited speaker against receipts; adjusted reimbursement for intra- and intercontinental travel is allowed. This $2000 support for invited speakers should be maintained by the LOC under all circumstances.

A list of at least two confirmed invited speakers per symposium should be requested in response to the call for symposia.

Selection of the symposia

Most symposia are selected by the LOC on the basis of proposals and depending on whether the same topics were covered by symposia at recent SMBE meetings.

Symposia should reflect the broad diversity of interests in the SMBE community, not simply the most popular topics. Symposium organizers select abstracts for talks, taking speaker diversity into consideration (see Statement of diversity above) as well as diversity of career stage (student/postdoc/junior/senior investigators).

Symposium proposals should include a summary of the topic, why it is timely for the SMBE meeting, and which speakers have been invited and confirmed. If there are two or more proposals on the same topic, the LOC has a choice of selecting one proposal or merging two or more proposals. Merging two or more symposia either reduces the number of invited speakers that can be supported by SMBE or the number of slots available for contributed talks and is therefore discouraged.

Each symposium organizer can only select one talk from her/his own research group. That includes his/her own talk. In the event of too few submissions, exceptions to this rule may permit one additional talk from the organizer’s group, after consultation with the LOC.

The LOC selects the talks for the Open Symposium.

Timeslots

Recent conferences have settled on a structure where a ‘unit’ of time is 15 minutes. This includes time for questions (usually, 12 minutes for the talk and 3 minutes for questions and movement between rooms). This makes it especially important to have rooms in close proximity to each other. Invited speakers can be allocated 15 or 30 mins. It is also prudent to remind symposium organizers that delegates frequently move between symposia, so it is useful to allow one minute of moving time between talks (if adequate for travel between rooms) within the allocated 15 minutes and to be sure that the layout of seating is conducive to movement between rooms.. Some symposium organizers may choose to use the first 15 minutes to provide an overview of the study area at the beginning, but this is subject to time availability.

Selecting speakers

Each symposium of contributed talks will select its preferred speaker list from the list of contributed talk abstracts. It is best if a delegate is allowed to submit their abstract to more than one symposium (though logistically, it is probably best to restrict this to two symposia). When the symposium organizers are given their list of abstracts and delegates who wish to speak in their symposium, they can choose their preferred list of speakers. However, the exact details of this process are to be worked out by the LOC. In the end, the LOC will match delegates and symposia and communicate to both the symposium organizers and the delegates the outcome of this process. This decision should be reached before Early Bird registration closes as it affects many scientists’ travel funding, and no later than 4 months before the conference.

Poster sessions

Poster presenters frequently feel that they do not get adequate opportunity to present their work, so it is important that each poster presenter is given enough time both to talk to other delegates and to have the posters visible (at breaks, etc.). Poster sessions should have accompanying refreshments and each poster should have at least two sessions when they are available to be seen. Although not always possible, it is desirable to have sufficient space that all posters can be viewed throughout the meeting, so that participants (and poster judges) have plenty of opportunity for viewing. The website should also indicate when posters can go up. Poster space should only be made available to participants who have registered and sent payment, to minimize “no-shows.”

Social events

Please provide vegetarian/vegan options with all catering.

Breaks and catering

It is expected that the conference will provide morning coffee break, lunch on all days, afternoon coffee breaks on each day, preferably with some small snack (fruit, cookies, pastry, etc.), and poster sessions.

Welcome reception

This typically provides ample snacks, enough for all participants, in addition to at most one or two drink tickets. Additional drinks can usually be purchased at the bar.

Gala Dinner  (banquet)

Delegates can choose to pay extra for this dinner or choose not to attend.

This is the preferred venue for distributing awards, and awardees present at the meeting, including all Fitch participants, should have free Gala tickets. A few venues include an after-dinner speaker, and some venues include dancing Drink tickets may be provided at registration for the Gala, with additional drinks available for purchase.

Awards Ceremony

The preferred venue for the Awards Ceremony (which lasts about 20 minutes) is the Gala Dinner.

If the awards are not distributed at the Gala Dinner, then 20-30 minutes should be set aside for an Awards Ceremony in the middle of the last morning (to allow enough time for decisions to be made on poster prizes and to maximize attendance). This ceremony is usually combined with an invitation to the next meeting (10-15 minutes), but the Gala is the preferred venue for awards.

While not all poster participants typically attend the Gala, due to cost, unless it is covered in registration, not all participants attend a separate Awards Ceremony, due to other choices on the last day, including packing and checking out of the hotel.

Post-conference survey

Each delegate should be invited to evaluate the conference, either using a paper form that can be dropped into a box onsite or an online form that can be completed either on a computer or smart phone.  The survey should be organized by the PCO and its content checked by the SMBE Council representative before distribution.

Certificates of attendance

Some delegates will require a certificate of attendance for their home institutions or for funding agencies that have supported their travel. These certificates should be provided on request and made available at the conference venue or sent after the meeting.

Post meeting reporting

Meeting organizers are required to provide a summary document to the Council after the

meeting, including the diversity statistics of the meeting participants, (gender, geography, and career stage).

Awards (see http://www.smbe.org/smbe/AWARDS.aspx)

SMBE provides several types of pre-conference awards, which should be administered via the conference abstract submission system. It is essential that time is allowed for awardees to be chosen and applicants notified before Early Bird registration closes so that attendees can make informed financial decisions about registration options and travel.

Those receiving awards that include registration and travel need to pay in the first instance and will then be reimbursed by SMBE.  This applies to all but recipients of Registration-only awards, who need  a code to put in to the online registration system to avoid payment.

SMBE-appointed committees select the recipients of travel awards.  All award applicants should be SMBE members.

SMBE’s Faculty, Best Paper, Fitch, and best poster awards are presented at the Awards Ceremony. All awardess, including all eight Fitch presenters, attending the meeting are eligible for free Gala Dinner tickets.

1.     Faculty awards

Faculty award-winners are reimbursed for registration and travel to the meeting.

Recipients of these awards should all be given the opportunity to present talks at the meeting, either in an ordinary symposium or the special symposium or in slots set aside for them in the Open Symposium.  The Council members responsible for these awards should be informed of the latest dates that lectures can be incorporated  into the programme.

2.     Fitch awards

All those selected to present in the Fitch Symposium are eligible for a free Gala Dinner ticket, and will be reimbursed for travel and accommodation.

The Council will appoint two separate committees, one to review the initial applicants to the Fitch symposium and another to determine the winner among the 8 finalists (see timeline above). Banquet tickets should be reserved for the 8 finalists.

3.     Undergraduate mentoring and diversity travel awards

Award-winners are reimbursed for registration and a contribution toward travel to the meeting.

10 undergraduate mentoring and diversity awards are available each year to undergraduate students that submit abstracts. The total value of each of  these awards is $1500 to $2000, depending whether intercontinental travel is involved. This covers registration, with the rest intended for travel.   Registration fees are to be charged directly to SMBE, so that students do not have to pay themselves (the amount of registration cost being deducted from the final value of their award, and the award recipients informed at time of notification of the value of their award to be used for travel and lodging).

One or two SMBE Councillors assigned by the Council will take charge of this selection, with a recommended bias towards funding those selected to give oral presentations, keeping the Statement of Diversity in mind.

The process consists of finding a mentor for each student so that they can be guided through the conference. In addition, a dinner should be arranged for all 10 students, their 10 mentors and the Council members who organize the activity. The conference organizers should reserve 10 banquet tickets for the awardees (to be charged to SMBE) and liaise with the Councillors in order to find an appropriate restaurant for the mentoring dinner, which is usually on the first full day.). The Councillors will send the list of awardees and their details to the meeting organizers and the PCO so that they can be registered automatically.

All undergraduate awardees should present their posters in the same poster session and their posters grouped together.

4.     Graduate and postdoc travel awards

Award-winners are reimbursed for registration and travel to the meeting.

SMBE provides graduate and postdoc travel awards for the purpose of enhancing gender and geographic diversity. The awards are chosen from eligible applicants who are SMBE members and who have expressed a desire to be considered for such awards. The Past-President, usually in conjunction with the LOC, will head a committee to determine the awards.

5.     Poster awards

The poster prizes will be decided by a committee convened by the President-Elect. Poster prizes consist of up to 9 prizes of $500 each, to be distributed in the 3 categories of postdoc, graduate student, and undergraduate prizes (it does not have to be 3 each).

6.     Best GBE and MBE papers awards

Award recipients receive registration waivers, travel awards to attend the meeting, and a Gala ticket.

7.     Registration awards

These are registration only awards, and there are usually more of these than awards that include travel.

8.     Carer travel awards

SMBE provides additional travel awards for our members who are also primary carers (for example caring for children or dependent adults, including adult children with a disability or an elderly relative). This award can be used in the manner of choosing of the awardee, for example for procuring child care or dependent care at home (e.g., flying a relative to help at home while the delegate is at the meeting; hiring a professional). Priority will be given to early-career scientists and according to need (e.g., younger children, disabled children or adults).

Information about Carer Travel Awards should be included in emails promoting conference registration and applications should be through the registration system. The decision on who is granted an award will be made by a committee of at least one person designated by Council. It shall be noted that people in need of an early decision can email a request to the organizers and/or council member in charge of the Carer Travel Award process.  

Registration

Payment for registration

The online registration system should accept all major credit and debit cards using the conventional inputting mechanism.  Credit card fees charged to the conference should be less than 3% per transaction.

Registration fees

SMBE members receive discounted registration. The discount for SMBE members must be at least $30, but a higher differential between member and non-member registration is allowed. Students and postdocs should be given a further discounted registration rate as well; the discount should be larger for graduate students than for postdocs.  The conference registration page should allow conference delegates the opportunity to join SMBE on the spot, e.g. by linking to the SMBE website membership page in a new window (currently http://www.smbe.org/smbe/MEMBERSHIP.aspx). Finally, while most registrants will use the website, it should also be possible to register onsite (‘walk-ins’).

Registration data

Registration data, including lists of delegates, should only be given to SMBE officials and used for SMBE business.  Third parties, including organizers of future conferences, should not be given the lists without express permission from SMBE.

This determines eligibility for certain awards and allows SMBE to maintain a participant database with student or postdoc status recorded (this is essential for determining poster and travel award eligibility, for instance). The conference organizers must maintain a database of participants with this information, as well as abstract numbers and titles as separate entries, email addresses, affiliations, etc.

Registration should include declarations of:

·  career stage (faculty, postdoc, graduate student, undergraduate, other)

gender,(with both a write-in option for non-gender conforming participants who prefer to specify and the option omit             this question).

Registration giveaways at the meeting

Printed conference material should be kept to a minimum. Sponsors should be encouraged to provide advertisements and information on the conference website or app or instead of printed flyers.

Badges

Each delegate should be provided with a badge. This must not include advertising promotion for any journal or society other than MBE/GBE and SMBE, though non-journal sponsors may sponsor lanyards. It is desirable to have badges that designate Editors and Associate Editors of the journals (sometimes provided by the MBE EiC) as well as a separate designation for Council members, and/or speakers, though this is the option of the organizers.

Other swag (bags, bottles, USB thumb drives, etc.)

Should be kept to a minimum to reduce environmental impact and should avoid advertising for journals directly competing with society journals.  

Conference website, programme, and app

SMBE conference promotion should consider environmental impact and minimize the use of printed materials.

Website

Must include:

promotion of travel and child care awards

SMBE policies on harassment and broadcasting (text in Appendix to this document)

All images either posted online or used in emails related to the conference should be approved by the Council liaison and take gender balance and other demographic issues into consideration, regarding the people shown in the images. When possible, images from previous SMBE meetings should be used.

Programme

The timetable should ideally be available in three formats:

●       “at-a-glance” format, simply detailing the session/symposia times and locations.

●       a more detailed version with each speaker shown in column format so that parallel talks are on the same row. This helps         participants plan their schedule. Once the meeting starts, it should be updated live online (or at least daily), since changes       do arise.

●       a detailed online-only booklet with each speaker listed along with all co-authors, affiliations, and abstract.

Be sure that all authors are visible in the complete online program, not just the presenting author, since many people choose to attend a talk based on the laboratory or senior author. It is helpful if this information can be provided in column format.

The programme should include SMBE policies on harassment and broadcasting (text in Appendix) and an email contact to report any violations of these policies. 

The most updated printed or printable conference programme should be the version with concurrent sessions in columns and concurrent talks in rows to make it easy to choose a path.

Additional requirements for the online programme

A participant list should be provided in the web programme.

The entire conference program, complete with timetables, should be made available for download to laptops or mobile devices, usually in PDF or Excel format.

The online programme should also contain all the logistical details for the conference, including the best and most cost-effective means of ground and air transportation to the meeting location.

Essential conference app features

●       Available in both iPhone and Android formats

●       Useable offline, since many travelers do not have a data plan and some hotels charge fees for wifi. Wifi quality can also be unreliable at large meeting venues.

●       If possible should not require registration (unless necessary for those who want  to customize it, for example to create a personalized program)

●       Updateable and updated daily

●       Include first author name, surname, and talk title, hyperlinked to abstract with all authors.

●       Allow announcements

●       Include SMBE policies on harassment and social media (text in Appendix) with quick email link to report violations

●       Include quick link so that a poster presenter can invite another meeting participant to her/his poster. (This should not require composing an email each time.)

●        Include, if possible, the ability to create a personalized schedule, selecting talks and/or abstracts to attend, by clicking on (such as “liking” or saving to schedule) either the talk title, speaker name, or abstract from any of its views.  This may include the option to set reminders. Reminders, alerts, or notifications (for example of poster sessions closing or a talk about to start) should always be inaudible.

Venue

Rooms

The conference venue should have at least one room that can hold at least 80% of delegates. Past experience indicates that for the plenary talks approximately 80% of the delegates will attend. Therefore, it is preferable that there is a room to hold this number. If this is not possible, then there should be a facility to relay the plenary lectures to another comfortable room via video link.

The venue should additionally have enough rooms for all parallel sessions and these should be sufficiently large to accommodate approximately one third of the conference, given the difficulty in predicting the numbers of delegates that attend any given talk. The rooms should be located no more than a 1-2 min walk from each other and have seating or aisles arranged to facilitate movement between sessions.

Kindly ask the venue to refrain from using air freshener during the conference in all locations, including registration desk and lobbies. Some participants are allergic to it and it exposes all participants to poor air quality.

Free, secure wifi should be available throughout the venue.

Onsite child care

Organizers will arrange for onsite (in the same building as the conference) child care, as this is an issue of great importance to the members of the Society. SMBE will help defray the cost of child care. Please communicate early and often with the Society as to the costs, barriers and opportunities for child care. Ideally the onsite location should be no more than a 5 minute walk from the sessions but not right next to a room where there are talks. Parents need quick access but the sound level can be that of a play-room setting.

Speaker set-up

There should be a set-up room for speakers to check their presentations. The preferred presentation file format is pdf, but ideally both Powerpoint and Keynote should be accepted. Both modern (current OS) Apple and PC computers should be provided for presenters.

Insurance

The LOC is responsible for liaising with SMBE and the PCO to ensure that all insurance requirements are met.

Appendix 1: SMBE policies

Policy on harassment, discrimination and liability
SMBE and the Annual Meeting organizers are dedicated to providing a safe, hospitable, and productive environment for all attendees. Accordingly, the SMBE Annual Meeting prohibits all forms of discrimination and harassment. Behaviour that undermines the integrity of intellectual discourse and interactions will not be tolerated. This applies to all conference participants, including staff, volunteers, and attendees. If a participant engages in harassing or discriminatory behaviour, the SMBE Annual Meeting organizers reserve the right to take action ranging from a simple warning to the offender to expulsion from the conference. If you have a question or concern about this policy or would like to report an incident involving yourself or another person, please contact any member of the Local Organizing Committee or email [email address for the appropriate year’s conference PCO]. We take such issues seriously and will maintain your confidentiality (unless legally compelled otherwise). Neither SMBE nor the SMBE Annual Meeting organizers shall be responsible for any defamatory, offensive, or illegal conduct of Meeting participants, and shall not be held liable for personal injury, property damage, theft or damage of any kind suffered by the participants at or in connection with the SMBE Annual Meeting.

Broadcasting policy
The SMBE Annual Meeting supports the communication and discussion of science. Information presented at the Meeting (in oral or poster format) may be reported and discussed by attendees and science writers via blogs, Twitter, or other formats, unless any of the authors requests otherwise. We do request that communications are respectful and do not directly reproduce visual materials (e.g., no posting of photos of slides or posters) unless permission is obtained from the presenter or if they have already made this information freely available in an open-source forum. If a presenter does not want information from his/her presentation to be photographed at all, or broadcast, they should make this clear in their talk/poster and we ask that attendees respect this. If you have questions or concerns about this policy, or would like to report an abuse of it, please contact any member of the Local Organizing Committee or email [email address for that year’s conference PCO].

Appendix 2: Call for proposals for conference

The President-Elect issues a call for proposals five years (e.g. call issued in 2017 for meeting in 2021) before the conference year, following the rotation below:

●       North America

●       Europe

●       Rest of the World

Applicants will be required to submit written proposals following a standard template to SMBE Council.  Applicants are required to work with SMBE’s designated PCO.




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Fri, 03 Aug 2018 00:00:00 GMT

Abstract
Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (∼100 bp), widely distributed (comprising ∼5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80×) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human “neutralome,” comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.

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Wed, 18 Jul 2018 00:00:00 GMT

Abstract
Thermal tolerance is a key determinant of species distribution. Despite much study, the genetic basis of adaptive evolution of thermal tolerance, including the relative contributions of transcriptional regulation versus protein evolution, remains unclear. Populations of the intertidal copepod Tigriopus californicus are adapted to local thermal regimes across their broad geographic range. Upon thermal stress, adults from a heat tolerant southern population, San Diego (SD), upregulate several heat shock proteins (HSPs) to higher levels than those from a less tolerant northern population, Santa Cruz (SC). Suppression of a specific HSP, HSPB1, significantly reduces T. californicus survival following acute heat stress. Sequencing of HSPB1 revealed population specific nucleotide substitutions in both promoter and coding regions of the gene. HSPB1 promoters from heat tolerant populations contain two canonical heat shock elements (HSEs), the binding sites for heat shock transcription factor (HSF), whereas less tolerant populations have mutations in these conserved motifs. Allele specific expression of HSPB1 in F1 hybrids between tolerant and less tolerant populations showed significantly biased expression favoring alleles from tolerant populations and supporting the adaptive divergence in these cis-regulatory variants. The functional impact of population-specific nonsynonymous substitutions in HSPB1 coding sequences was tested by assessing the thermal stabilization properties of SD versus SC HSPB1 protein variants. Recombinant HSPB1 from the southern SD population showed greater capacity for protecting protein structure under elevated temperature. Our results indicate that both regulatory and protein coding sequence evolution within a single gene appear to contribute to thermal tolerance phenotypes and local adaptation among conspecific populations.

Accurate Detection of Convergent Amino-Acid Evolution with PCOC

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Abstract
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Fri, 29 Jun 2018 00:00:00 GMT

Abstract
Human skin color diversity is considered an adaptation to environmental conditions such as UV radiation. Investigations into the genetic bases of such adaptation have identified a group of pigmentation genes contributing to skin color diversity in African and non-African populations. Here, we present a population analysis of the pigmentation gene KITLG with previously reported signal of Darwinian positive selection in both European and East Asian populations. We demonstrated that there had been recurrent selective events in the upstream and the downstream regions of KITLG in Eurasian populations. More importantly, besides the expected selection on the KITLG variants favoring light skin in coping with the weak UV radiation at high latitude, we observed a KITLG variant showing adaptation to winter temperature. In particular, compared with UV radiation, winter temperature showed a much stronger correlation with the prevalence of the presumably adaptive KITLG allele in Asian populations. This observation was further supported by the in vitro functional test at low temperature. Consequently, the pleiotropic effects of KITLG, that is, pigmentation and thermogenesis were both targeted by natural selection that acted on different KITLG sequence variants, contributing to the adaptation of Eurasians to both UV radiation and winter temperature at high latitude areas.

Estimating TimeTrees with MEGA and the TimeTree Resource

Thu, 21 Jun 2018 00:00:00 GMT

Abstract
The main outcome of molecular dating, the timetree, provides crucial information for understanding the evolutionary history of lineages and is a requirement of several evolutionary analyses. Although essential, the estimation of divergence times from molecular data is frequently regarded as a complicated task. However, establishing biological timescales can be performed in a straightforward manner, even with large, genome-wide data sets. This protocol presents all the necessary steps to estimate a timetree in the program MEGA X. It also illustrates how the TimeTree resource can be a useful tool to obtain chronological information based on previous studies, therefore yielding calibration boundaries.

Loter: A Software Package to Infer Local Ancestry for a Wide Range of Species

Wed, 20 Jun 2018 00:00:00 GMT

Abstract
Admixture between populations provides opportunity to study biological adaptation and phenotypic variation. Admixture studies rely on local ancestry inference for admixed individuals, which consists of computing at each locus the number of copies that originate from ancestral source populations. Existing software packages for local ancestry inference are tuned to provide accurate results on human data and recent admixture events. Here, we introduce Loter, an open-source software package that does not require any biological parameter besides haplotype data in order to make local ancestry inference available for a wide range of species. Using simulations, we compare the performance of Loter to HAPMIX, LAMP-LD, and RFMix. HAPMIX is the only software severely impacted by imperfect haplotype reconstruction. Loter is the less impacted software by increasing admixture time when considering simulated and admixed human genotypes. For simulations of admixed Populus genotypes, Loter and LAMP-LD are robust to increasing admixture times by contrast to RFMix. When comparing length of reconstructed and true ancestry tracts, Loter and LAMP-LD provide results whose accuracy is again more robust than RFMix to increasing admixture times. We apply Loter to individuals resulting from admixture between Populus trichocarpa and Populus balsamifera and lengths of ancestry tracts indicate that admixture took place ∼100 generations ago. We expect that providing a rapid and parameter-free software for local ancestry inference will make more accessible genomic studies about admixture processes.

Population Genomics Provide Insights into the Evolution and Adaptation of the Eastern Honey Bee (Apis cerana)

Wed, 20 Jun 2018 00:00:00 GMT

Abstract
The mechanisms by which organisms adapt to variable environments are a fundamental question in evolutionary biology and are important to protect important species in response to a changing climate. An interesting candidate to study this question is the honey bee Apis cerana, a keystone pollinator with a wide distribution throughout a large variety of climates, that exhibits rapid dispersal. Here, we resequenced the genome of 180 A. cerana individuals from 18 populations throughout China. Using a population genomics approach, we observed considerable genetic variation in A. cerana. Patterns of genetic differentiation indicate high divergence at the subspecies level, and physical barriers rather than distance are the driving force for population divergence. Estimations of divergence time suggested that the main branches diverged between 300 and 500 Ka. Analyses of the population history revealed a substantial influence of the Earth’s climate on the effective population size of A. cerana, as increased population sizes were observed during warmer periods. Further analyses identified candidate genes under natural selection that are potentially related to honey bee cognition, temperature adaptation, and olfactory. Based on our results, A. cerana may have great potential in response to climate change. Our study provides fundamental knowledge of the evolution and adaptation of A. cerana.

Relative Evolutionary Rates in Proteins Are Largely Insensitive to the Substitution Model

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
The relative evolutionary rates at individual sites in proteins are informative measures of conservation or adaptation. Often used as evolutionarily aware conservation scores, relative rates reveal key functional or strongly selected residues. Estimating rates in a phylogenetic context requires specifying a protein substitution model, which is typically a phenomenological model trained on a large empirical data set. A strong emphasis has traditionally been placed on selecting the “best-fit” model, with the implicit understanding that suboptimal or otherwise ill-fitting models might bias inferences. However, the pervasiveness and degree of such bias has not been systematically examined. We investigated how model choice impacts site-wise relative rates in a large set of empirical protein alignments. We compared models designed for use on any general protein, models designed for specific domains of life, and the simple equal-rates Jukes Cantor-style model (JC). As expected, information theoretic measures showed overwhelming evidence that some models fit the data decidedly better than others. By contrast, estimates of site-specific evolutionary rates were impressively insensitive to the substitution model used, revealing an unexpected degree of robustness to potential model misspecification. A deeper examination of the fewer than 5% of sites for which model inferences differed in a meaningful way showed that the JC model could uniquely identify rapidly evolving sites that models with empirically derived exchangeabilities failed to detect. We conclude that relative protein rates appear robust to the applied substitution model, and any sensible model of protein evolution, regardless of its fit to the data, should produce broadly consistent evolutionary rates.

Secondary Plastids of Euglenids and Chlorarachniophytes Function with a Mix of Genes of Red and Green Algal Ancestry

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
Endosymbiosis has been common all along eukaryotic evolution, providing opportunities for genomic and organellar innovation. Plastids are a prominent example. After the primary endosymbiosis of the cyanobacterial plastid ancestor, photosynthesis spread in many eukaryotic lineages via secondary endosymbioses involving red or green algal endosymbionts and diverse heterotrophic hosts. However, the number of secondary endosymbioses and how they occurred remain poorly understood. In particular, contrasting patterns of endosymbiotic gene transfer have been detected and subjected to various interpretations. In this context, accurate detection of endosymbiotic gene transfers is essential to avoid wrong evolutionary conclusions. We have assembled a strictly selected set of markers that provides robust phylogenomic evidence suggesting that nuclear genes involved in the function and maintenance of green secondary plastids in chlorarachniophytes and euglenids have unexpected mixed red and green algal origins. This mixed ancestry contrasts with the clear red algal origin of most nuclear genes carrying similar functions in secondary algae with red plastids.

Phylogenomic Evidence Overturns Current Conceptions of Social Evolution in Wasps (Vespidae)

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
The hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral castes → eusociality with preimaginal caste-biasing (PCB) → morphologically differentiated castes). Here, we infer the phylogeny of Vespidae using sequence data generated via anchored hybrid enrichment from 378 loci across 136 vespid species and perform ancestral state reconstructions to test whether rudimentary and monomorphic castes characterized the initial stages of eusocial evolution. Our results reject the single origin of eusociality hypothesis, contest the supposition that eusociality emerged from a casteless nest-sharing ancestor, and suggest that eusociality in Polistinae + Vespinae began with castes having morphological differences. An abrupt appearance of castes with ontogenetically established morphophysiological differences conflicts with the current conception of stepwise social evolution and suggests that the climb up the ladder of sociality does not occur through sequential mutation. Phenotypic plasticity and standing genetic variation could explain how cooperative brood care evolved in concert with nest-sharing and how morphologically dissimilar castes arose without a rudimentary intermediate. Furthermore, PCB at the outset of eusociality implicates a subsocial route to eusociality in Polistinae + Vespinae, emphasizing the role of mother–daughter interactions and subfertility (i.e. the cost component of kin selection) in the origin of workers.

Homeobox Gene Duplication and Divergence in Arachnids

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
Homeobox genes are key toolkit genes that regulate the development of metazoans and changes in their regulation and copy number have contributed to the evolution of phenotypic diversity. We recently identified a whole genome duplication (WGD) event that occurred in an ancestor of spiders and scorpions (Arachnopulmonata), and that many homeobox genes, including two Hox clusters, appear to have been retained in arachnopulmonates. To better understand the consequences of this ancient WGD and the evolution of arachnid homeobox genes, we have characterized and compared the homeobox repertoires in a range of arachnids. We found that many families and clusters of these genes are duplicated in all studied arachnopulmonates (Parasteatoda tepidariorum, Pholcus phalangioides, Centruroides sculpturatus, and Mesobuthus martensii) compared with nonarachnopulmonate arachnids (Phalangium opilio, Neobisium carcinoides, Hesperochernes sp., and Ixodes scapularis). To assess divergence in the roles of homeobox ohnologs, we analyzed the expression of P. tepidariorum homeobox genes during embryogenesis and found pervasive changes in the level and timing of their expression. Furthermore, we compared the spatial expression of a subset of P. tepidariorum ohnologs with their single copy orthologs in P. opilio embryos. We found evidence for likely subfunctionlization and neofunctionalization of these genes in the spider. Overall our results show a high level of retention of homeobox genes in spiders and scorpions post-WGD, which is likely to have made a major contribution to their developmental evolution and diversification through pervasive subfunctionlization and neofunctionalization, and paralleling the outcomes of WGD in vertebrates.

Insect Retroelements Provide Novel Insights into the Origin of Hepatitis B Viruses

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
The origin of hepadnaviruses (Hepadnaviridae), a group of reverse-transcribing DNA viruses that infect vertebrates, remains mysterious. All the known retrotransposons are only distantly related to hepadnaviruses. Here, we report the discovery of two novel lineages of retroelements, which we designate hepadnavirus-like retroelement (HEART1 and HEART2), within the insect genomes through screening 1, 095 eukaryotic genomes. Both phylogenetic and similarity analyses suggest that the HEART retroelements represent the closest nonviral relatives of hepadnaviruses so far. The discovery of HEART retroelements narrows down the evolutionary gap between hepadnaviruses and retrotransposons and might thus provide unique insights into the origin and evolution of hepadnaviruses.

Evolution of Sex-Biased Gene Expression and Dosage Compensation in the Eye and Brain of Heliconius Butterflies

Tue, 19 Jun 2018 00:00:00 GMT

Abstract
Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. In this study, we performed a comparative sex-biased gene expression analysis of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. We found that the degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Krüppel-homolog 1 and CG9492. We also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, we found dosage compensation in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection.

Identification and Characterization of Novel Conserved Domains in Metazoan Zic Proteins

Thu, 14 Jun 2018 00:00:00 GMT

Abstract
Zic family genes encode C2H2-type zinc finger proteins that act as critical toolkit proteins in the metazoan body plan establishment. In this study, we searched evolutionarily conserved domains (CDs) among 121 Zic protein sequences from 22 animal phyla and 40 classes, and addressed their evolutionary significance. The collected sequences included those from poriferans and orthonectids. We discovered seven new CDs, CD0–CD6, (in order from the N- to C-terminus) using the most conserved Zic protein sequences from Deuterostomia (Hemichordata and Cephalochordata), Lophotrochozoa (Cephalopoda and Brachiopoda), and Ecdysozoa (Chelicerata and Priapulida). Subsequently, we analyzed the evolutionary history of Zic CDs including the known CDs (ZOC, ZFD, ZFNC, and ZFCC). All Zic CDs are predicted to have existed in a bilaterian ancestor. During evolution, they have degenerated in a taxa-selective manner with significant correlations among CDs. The N terminal CD (CD0) was largely lost, but was observed in Brachiopoda, Priapulida, Hemichordata, Echinodermata, and Cephalochordata, and the C terminal CD (CD6) was highly conserved in conserved-type-Zic possessing taxa, but was truncated in vertebrate Zic gene paralogues (Zic1/2/3), generating a vertebrate-specific C-terminus critical for transcriptional regulation. ZOC was preferentially conserved in insects and in an anthozoan paralogue, and it was bound to the homeodomain transcription factor Msx in a phylogenetically conserved manner. Accordingly, the extent of divergence of Msx and Zic CDs from their respective bilaterian ancestors is strongly correlated. These results suggest that coordinated divergence among the toolkit CDs and among toolkit proteins is involved in the divergence of metazoan body plans.

On the Origin of Isoprenoid Biosynthesis

Thu, 14 Jun 2018 00:00:00 GMT

Abstract
Isoprenoids and their derivatives represent the largest group of organic compounds in nature and are distributed universally in the three domains of life. Isoprenoids are biosynthesized from isoprenyl diphosphate units, generated by two distinctive biosynthetic pathways: mevalonate pathway and methylerthritol 4-phosphate pathway. Archaea and eukaryotes exclusively have the former pathway, while most bacteria have the latter. Some bacteria, however, are known to possess the mevalonate pathway genes. Understanding the evolutionary history of these two isoprenoid biosynthesis pathways in each domain of life is critical since isoprenoids are so interweaved in the architecture of life that they would have had indispensable roles in the early evolution of life. Our study provides a detailed phylogenetic analysis of enzymes involved in the mevalonate pathway and sheds new light on its evolutionary history. The results suggest that a potential mevalonate pathway is present in the recently discovered superphylum Candidate Phyla Radiation (CPR), and further suggest a strong evolutionary relationship exists between archaea and CPR. Interestingly, CPR harbors the characteristics of both the bacterial-type and archaeal-type mevalonate pathways and may retain signatures regarding the ancestral isoprenoid biosynthesis pathway in the last universal common ancestor. Our study supports the ancient origin of the mevalonate pathway in the three domains of life as previously inferred, but concludes that the evolution of the mevalonate pathway was more complex.

Host Range and Genetic Plasticity Explain the Coexistence of Integrative and Extrachromosomal Mobile Genetic Elements

Thu, 14 Jun 2018 00:00:00 GMT

Abstract
Self-transmissible mobile genetic elements drive horizontal gene transfer between prokaryotes. Some of these elements integrate in the chromosome, whereas others replicate autonomously as plasmids. Recent works showed the existence of few differences, and occasional interconversion, between the two types of elements. Here, we enquired on why evolutionary processes have maintained the two types of mobile genetic elements by comparing integrative and conjugative elements (ICE) with extrachromosomal ones (conjugative plasmids) of the highly abundant MPFT conjugative type. We observed that plasmids encode more replicases, partition systems, and antibiotic resistance genes, whereas ICEs encode more integrases and metabolism-associated genes. ICEs and plasmids have similar average sizes, but plasmids are much more variable, have more DNA repeats, and exchange genes more frequently. On the other hand, we found that ICEs are more frequently transferred between distant taxa. We propose a model where the different genetic plasticity and amplitude of host range between elements explain the co-occurrence of integrative and extrachromosomal elements in microbial populations. In particular, the conversion from ICE to plasmid allows ICE to be more plastic, while the conversion from plasmid to ICE allows the expansion of the element’s host range.

Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection

Fri, 08 Jun 2018 00:00:00 GMT

Abstract
Toll-like receptors (TLRs) are key sensor molecules in vertebrates triggering initial phases of immune responses to pathogens. The avian TLR family typically consists of ten receptors, each adapted to distinct ligands. To understand the complex evolutionary history of each avian TLR, we analyzed all members of the TLR family in the whole genome assemblies and target sequence data of 63 bird species covering all major avian clades. Our results indicate that gene duplication events most probably occurred in TLR1 before synapsids diversified from sauropsids. Unlike mammals, ssRNA-recognizing TLR7 has duplicated independently in several avian taxa, while flagellin-sensing TLR5 has pseudogenized multiple times in bird phylogeny. Our analysis revealed stronger positive, diversifying selection acting in TLR5 and the three-domain TLRs (TLR10 [TLR1A], TLR1 [TLR1B], TLR2A, TLR2B, TLR4) that face the extracellular space and bind complex ligands than in single-domain TLR15 and endosomal TLRs (TLR3, TLR7, TLR21). In total, 84 out of 306 positively selected sites were predicted to harbor substitutions dramatically changing the amino acid physicochemical properties. Furthermore, 105 positively selected sites were located in the known functionally relevant TLR regions. We found evidence for convergent evolution acting between birds and mammals at 54 of these sites. Our comparative study provides a comprehensive insight into the evolution of avian TLR genetic variability. Besides describing the history of avian TLR gene gain and gene loss, we also identified candidate positions in the receptors that have been likely shaped by direct molecular host–pathogen coevolutionary interactions and most probably play key functional roles in birds.

Divergent Allele Advantage at Human MHC Genes: Signatures of Past and Ongoing Selection

Fri, 08 Jun 2018 00:00:00 GMT

Abstract
The highly polymorphic genes of the major histocompatibility complex (MHC) play a key role in adaptive immunity. Divergent allele advantage, a mechanism of balancing selection, is proposed to contribute to their exceptional polymorphism. It assumes that MHC genotypes with more divergent alleles allow for broader antigen-presentation to immune effector cells, by that increasing immunocompetence. However, the direct correlation between pairwise sequence divergence and the corresponding repertoire of bound peptides has not been studied systematically across different MHC genes. Here, we investigated this relationship for five key classical human MHC genes (human leukocyte antigen; HLA-A, -B, -C, -DRB1, and -DQB1), using allele-specific computational binding prediction to 118,097 peptides derived from a broad range of human pathogens. For all five human MHC genes, the genetic distance between two alleles of a heterozygous genotype was positively correlated with the total number of peptides bound by these two alleles. In accordance with the major antigen-presentation pathway of MHC class I molecules, HLA-B and HLA-C alleles showed particularly strong correlations for peptides derived from intracellular pathogens. Intriguingly, this bias coincides with distinct protein compositions between intra- and extracellular pathogens, possibly suggesting adaptation of MHC I molecules to present specifically intracellular peptides. Eventually, we observed significant positive correlations between an allele’s average divergence and its population frequency. Overall, our results support the divergent allele advantage as a meaningful quantitative mechanism through which pathogen-mediated selection leads to the evolution of MHC diversity.

Bootstrap and Rogue Identification Tests for Phylogenetic Analyses

Thu, 07 Jun 2018 00:00:00 GMT

Abstract
Most phylogenetic tree-generating programs produce a fully dichotomous phylogenetic tree. However, as different markers may produce distinct topologies for the same set of organisms, topological tests are used to estimate the statistical reliability of the clades. In this protocol, we provide step-by-step instructions on how to perform the widely used bootstrap test using MEGA. However, a single unstable lineage, also known as a rogue lineage, may decrease the bootstrap proportions in many branches of the tree. This occurs because rogue taxa tend to bounce between clades from one pseudo-replicate to the next, lowering bootstrap proportions for many correct clades. Thus, it is important to identify and exclude rogue taxa before initiating a final phylogenetic analysis; here, we provide this protocol using the RogueNaRok platform.

Convergent Evolution at the Pathway Level: Predictable Regulatory Changes during Flower Color Transitions

Thu, 07 Jun 2018 00:00:00 GMT

Abstract
The predictability of evolution, or whether lineages repeatedly follow the same evolutionary trajectories during phenotypic convergence remains an open question of evolutionary biology. In this study, we investigate evolutionary convergence at the biochemical pathway level and test the predictability of evolution using floral anthocyanin pigmentation, a trait with a well-understood genetic and regulatory basis. We reconstructed the evolution of floral anthocyanin content across 28 species of the Andean clade Iochrominae (Solanaceae) and investigated how shifts in pigmentation are related to changes in expression of seven key anthocyanin pathway genes. We used phylogenetic multivariate analysis of gene expression to test for phenotypic and developmental convergence at a macroevolutionary scale. Our results show that the four independent losses of the ancestral pigment delphinidin involved convergent losses of expression of the three late pathway genes (F3′5′h, Dfr, and Ans). Transitions between pigment types affecting floral hue (e.g., blue to red) involve changes to the expression of branching genes F3′h and F3′5′h, while the expression levels of early steps of the pathway are strongly conserved in all species. These patterns support the idea that the macroevolution of floral pigmentation follows predictable evolutionary trajectories to reach convergent phenotype space, repeatedly involving regulatory changes. This is likely driven by constraints at the pathway level, such as pleiotropy and regulatory structure.

Intratumor Heterogeneity and Circulating Tumor Cell Clusters

Mon, 12 Jun 2017 00:00:00 GMT

Abstract
Genetic diversity plays a central role in tumor progression, metastasis, and resistance to treatment. Experiments are shedding light on this diversity at ever finer scales, but interpretation is challenging. Using recent progress in numerical models, we simulate macroscopic tumors to investigate the interplay between growth dynamics, microscopic composition, and circulating tumor cell cluster diversity. We find that modest differences in growth parameters can profoundly change microscopic diversity. Simple outwards expansion leads to spatially segregated clones and low diversity, as expected. However, a modest cell turnover can result in an increased number of divisions and mixing among clones resulting in increased microscopic diversity in the tumor core. Using simulations to estimate power to detect such spatial trends, we find that multi-region sequencing data from contemporary studies is marginally powered to detect the predicted effects. Slightly larger samples, improved detection of rare variants, or sequencing of smaller biopsies or circulating tumor cell clusters would allow one to distinguish between leading models of tumor evolution. The genetic composition of circulating tumor cell clusters, which can be obtained from noninvasive blood draws, is therefore informative about tumor evolution and its metastatic potential.

GBE | Most Read

Genome Biology & Evolution

Evolution of gustatory receptor gene family provides insights into adaptation to diverse host plants in nymphalid butterflies

Thu, 06 Sep 2018 00:00:00 GMT

Hiromu C. Suzuki, Katsuhisa Ozaki, Takashi Makino, Hironobu Uchiyama, Shunsuke Yajima, and Masakado Kawata

Deep Sequencing of Fosmid Clones Indicates Gene Conversion in the Male-Specific Region of the Giant Panda Y Chromosome

Mon, 13 Aug 2018 00:00:00 GMT

Abstract
The giant panda (Ailuropoda melanoleuca) is popular around the world and is widely recognized as a symbol of nature conservation. A draft genome of the giant panda is now available, but its Y chromosome has not been sequenced. Y chromosome data are necessary for study of sex chromosome evolution, male development, and spermatogenesis. Thus, in the present study, we sequenced two parts of the giant panda Y chromosome utilizing a male giant panda fosmid library. The sequencing data were assembled into two contigs, each ∼100 kb in length with no gaps, providing high-quality resources for studying the giant panda Y chromosome. Annotation and transposable element comparison indicates varied evolutionary pressure in different regions of the Y chromosome. Two genes, zinc finger protein, Y-linked (ZFY) and lysine demethylase 5D (KDM5D), were annotated and gene conversion was observed for ZFY exon 7. Phylogenetic analysis also revealed that this gene conversion event happened independently in multiple mammalian lineages, indicating a putative mechanism to maintain the function of this particular gene on the Y chromosome. Furthermore, a transposition event, discovered through comparative alignment with the giant panda X chromosome sequence, may be involved in the process of gaining new genes on the Y chromosome. Thus, these newly obtained Y chromosome sequences provide valuable insights into the genomic patterns of the giant panda.

A Freeloader? The Highly Eroded Yet Large Genome of the Serratia symbiotica Symbiont of Cinara strobi

Thu, 09 Aug 2018 00:00:00 GMT

Abstract
Genome reduction is pervasive among maternally inherited bacterial endosymbionts. This genome reduction can eventually lead to serious deterioration of essential metabolic pathways, thus rendering an obligate endosymbiont unable to provide essential nutrients to its host. This loss of essential pathways can lead to either symbiont complementation (sharing of the nutrient production with a novel co-obligate symbiont) or symbiont replacement (complete takeover of nutrient production by the novel symbiont). However, the process by which these two evolutionary events happen remains somewhat enigmatic by the lack of examples of intermediate stages of this process. Cinara aphids (Hemiptera: Aphididae) typically harbor two obligate bacterial symbionts: Buchnera and Serratia symbiotica. However, the latter has been replaced by different bacterial taxa in specific lineages, and thus species within this aphid lineage could provide important clues into the process of symbiont replacement. In the present study, using 16S rRNA high-throughput amplicon sequencing, we determined that the aphid Cinara strobi harbors not two, but three fixed bacterial symbionts: Buchnera aphidicola, a Sodalis sp., and S. symbiotica. Through genome assembly and genome-based metabolic inference, we have found that only the first two symbionts (Buchnera and Sodalis) actually contribute to the hosts’ supply of essential nutrients while S. symbiotica has become unable to contribute towards this task. We found that S. symbiotica has a rather large and highly eroded genome which codes only for a few proteins and displays extensive pseudogenization. Thus, we propose an ongoing symbiont replacement within C. strobi, in which a once “competent” S. symbiotica does no longer contribute towards the beneficial association. These results suggest that in dual symbiotic systems, when a substitute cosymbiont is available, genome deterioration can precede genome reduction and a symbiont can be maintained despite the apparent lack of benefit to its host.

Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs

Wed, 08 Aug 2018 00:00:00 GMT

Abstract
Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.

Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were Present in the First Bilaterians

Wed, 08 Aug 2018 00:00:00 GMT

Abstract
Homeodomain transcription factors are involved in many developmental processes across animals and have been linked to body plan evolution. Detailed classifications of these proteins identified 11 distinct classes of homeodomain proteins in animal genomes, each harboring specific sequence composition and protein domains. Although humans contain the full set of classes, Drosophila melanogaster and Caenorhabditis elegans each lack one specific class. Furthermore, representative previous analyses in sponges, ctenophores, and cnidarians could not identify several classes in those nonbilaterian metazoan taxa. Consequently, it is currently unknown when certain homeodomain protein classes first evolved during animal evolution. Here, we investigate representatives of the sister group to all remaining bilaterians, the Xenacoelomorpha. We analyzed three acoel, one nemertodermatid, and one Xenoturbella transcriptomes and identified their expressed homeodomain protein content. We report the identification of representatives of all 11 classes of animal homeodomain transcription factors in Xenacoelomorpha and we describe and classify their homeobox genes relative to the established animal homeodomain protein families. Our findings suggest that the genome of the last common ancestor of bilateria contained the full set of these gene classes, supporting the subsequent diversification of bilaterians.

A Revised Spiralian Homeobox Gene Classification Incorporating New Polychaete Transcriptomes Reveals a Diverse TALE Class and a Divergent Hox Gene

Sat, 07 Jul 2018 00:00:00 GMT

Abstract
The diversity of mechanisms and capacity for regeneration across the Metazoa present an intriguing challenge in evolutionary biology, impacting on the burgeoning field of regenerative medicine. Broad taxonomic sampling is essential to improve our understanding of regeneration, and studies outside of the traditional model organisms have proved extremely informative. Within the historically understudied Spiralia, the Annelida have an impressive variety of tractable regenerative systems. The biomeralizing, blastema-less regeneration of the head appendage (operculum) of the serpulid polychaete keelworm Spirobranchus (formerly Pomatoceros) lamarcki is one such system. To profile potential regulatory mechanisms, we classified the homeobox gene content of opercular regeneration transcriptomes. As a result of retrieving several difficult-to-classify homeobox sequences, we performed an extensive search and phylogenetic analysis of the TALE and PRD-class homeobox gene content of a broad selection of lophotrochozoan genomes. These analyses contribute to our increasing understanding of the diversity, taxonomic extent, rapid evolution, and radical flexibility of these recently discovered homeobox gene radiations. Our expansion and integration of previous nomenclature systems helps to clarify their cryptic orthology. We also describe an unusual divergent S. lamarcki Antp gene, a previously unclassified lophotrochozoan orphan gene family (Lopx), and a number of novel Nk class orphan genes. The expression and potential involvement of many of these lineage- and clade-restricted homeobox genes in S. lamarcki operculum regeneration provides an example of diversity in regenerative mechanisms, as well as significantly improving our understanding of homeobox gene evolution.

In Cold Blood: Compositional Bias and Positive Selection Drive the High Evolutionary Rate of Vampire Bats Mitochondrial Genomes

Wed, 20 Jun 2018 00:00:00 GMT

Abstract
Mitochondrial genomes of animals have long been considered to evolve under the action of purifying selection. Nevertheless, there is increasing evidence that they can also undergo episodes of positive selection in response to shifts in physiological or environmental demands. Vampire bats experienced such a shift, as they are the only mammals feeding exclusively on blood and possessing anatomical adaptations to deal with the associated physiological requirements (e.g., ingestion of high amounts of liquid water and iron). We sequenced eight new chiropteran mitogenomes including two species of vampire bats, five representatives of other lineages of phyllostomids and one close outgroup. Conducting detailed comparative mitogenomic analyses, we found evidence for accelerated evolutionary rates at the nucleotide and amino acid levels in vampires. Moreover, the mitogenomes of vampire bats are characterized by an increased cytosine (C) content mirrored by a decrease in thymine (T) compared with other chiropterans. Proteins encoded by the vampire bat mitogenomes also exhibit a significant increase in threonine (Thr) and slight reductions in frequency of the hydrophobic residues isoleucine (Ile), valine (Val), methionine (Met), and phenylalanine (Phe). We show that these peculiar substitution patterns can be explained by the co-occurrence of both neutral (mutational bias) and adaptive (positive selection) processes. We propose that vampire bat mitogenomes may have been impacted by selection on mitochondrial proteins to accommodate the metabolism and nutritional qualities of blood meals.